Post on 18-Jul-2020
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
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STATISTICAL ANALYSIS PLAN
A Phase 1b/2a, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Plasma gelsolin (rhu-pGSN) Added to Standard of Care in Subjects Hospitalized for Acute
Community-acquired Pneumonia (CAP)
Protocol No.: BT-201
Product Code: rhu-pGSN
PREPARED FOR: BioAegis Therapeutics, Inc. (BTI) 675 US-1, North Brunswick Township, NJ 08902, USA Phone: +1 203-952-6373
PREPARED BY: Novotech (Australia) Pty Ltd Level 3, 235 Pyrmont Street Pyrmont, NSW, 2009 Australia
DATE OF ISSUE: 27 August 2018 (Draft Version 0.1) 19 September 2018 (Draft Version 0.5) 03 October 2018 (Final Draft 0.9) 02 November 2018 (Final 1.0) 03 December 2018 (Final 2.0 Amendment 1.0)
VERSION/STATUS: Final 2.0 Amendment 1.0
VERSION DATE: 03 December 2018
AUTHOR: Jan Steyn
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
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SUMMARY OF CHANGES FROM SAP VERSION 1.0
Section 11.2.2 page 25, the following text has been added:
Additionally, counts (%) of number subjects with values out of normal range at each scheduled time point will also be presented along with shift tables that will represent the changes in normal range categories across post-baseline time points.
Section 17, the following tables have been added:
No. Title Analysis
Population
14.3.4.1.2.1 SD: Summary of CBC Shifts from Baseline (Low, Normal, High) Safety 14.3.4.1.2.2 MAD: Summary of CBC Shifts from Baseline (Low, Normal, High) Safety 14.3.4.2.2.1 SD: Summary of Coagulation Shifts from Baseline
(Low, Normal, High) Safety
14.3.4.2.2.2 MAD: Summary of Coagulation Shifts from Baseline (Low, Normal, High) Safety
14.3.4.3.2.1 SD: Summary of Comprehesive Metabolic Profile Shifts from Baseline (Low, Normal, High)
Safety
14.3.4.3.2.2 MAD: Summary of Comprehesive Metabolic Profile Shifts from Baseline (Low, Normal, High) Safety
Section 18, the following listings have been added:
No. Title Analysis Population
16.2.8.1.2.1 SD: Abnormal CBC Intent-to-Treat 16.2.8.1.2.2 MAD: Abnormal CBC Intent-to-Treat 16.2.8.2.2.1 SD: Abnormal Coagulation Intent-to-Treat 16.2.8.2.2.2 MAD: Abnormal Coagulation Intent-to-Treat 16.2.8.3.2.1 SD: Abnormal Comprehensive Metabolic Profile Intent-to-Treat 16.2.8.3.2.2 MAD: Abnormal Comprehensive Metabolic Profile Intent-to-Treat
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Table of contents
1. INTRODUCTION .................................................................................................................... 8
2. PROJECT OVERVIEW ............................................................................................................ 9
2.1 Study Design ............................................................................................................................. 9
2.2 Objectives ................................................................................................................................. 9
2.3 Sample Size ............................................................................................................................. 10
2.4 Randomization ........................................................................................................................ 10
3. STATISTICAL CONSIDERATIONS ......................................................................................... 11
4. ANALYSIS POPULATIONS .................................................................................................... 13
4.1 Population Descriptions ......................................................................................................... 13
5. PROTOCOL DEVIATIONS..................................................................................................... 14
6. SUBJECT DISPOSITION ........................................................................................................ 15
7. DEMOGRAPHIC AND BASELINE INFORMATION ................................................................ 16
7.1 Demographics ......................................................................................................................... 16
7.2 Medical history ....................................................................................................................... 16
7.3 Pregnancy Test (Serum and Urine) ......................................................................................... 16
7.4 Serology .................................................................................................................................. 16
7.5 Other baseline characteristics ................................................................................................ 16
8. STUDY DRUG ADMINISTRATION ........................................................................................ 17
9. PHARMACOKINETICS (PK) .................................................................................................. 18
9.1 Definition of variables ............................................................................................................ 18
9.2 Biostatistical methods ............................................................................................................ 19
10. PHARMACODYNAMICS (Efficacy) ................................................................................... 22
10.1 Definition of variables ............................................................................................................ 22
10.2 Biostatistical methods ............................................................................................................ 22
11. SAFETY ............................................................................................................................ 23
11.1 Adverse Events ....................................................................................................................... 23
11.2 Safety Laboratory Assessments .............................................................................................. 24
11.3 Vital Signs Measurements ...................................................................................................... 26
11.4 12 - Lead Electrocardiogram (EKG) ......................................................................................... 27
11.5 Physical Examinations ............................................................................................................ 27
11.6 Outcome Prediction Models .................................................................................................. 27
11.7 Concomitant Medications ...................................................................................................... 28
11.8 Other safety evaluations ........................................................................................................ 28
12. IMMUNOGENICITY ENDPOINTS ..................................................................................... 30
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13. EXPLORATORY ENDPOINTS ............................................................................................ 31
14. HANDLING OF MISSING DATA........................................................................................ 32
15. CHANGES TO THE PLANNED ANALYSIS .......................................................................... 33
15.1 Final Analysis (End of Study) ................................................................................................... 34
16. SOFTWARE ..................................................................................................................... 35
17. TABLES ............................................................................................................................ 36
18. LISTINGS ......................................................................................................................... 39
19. FIGURES .......................................................................................................................... 42
20. APPENDICES ................................................................................................................... 43
21. REFERENCES ................................................................................................................... 44
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List of Abbreviations
Abbreviation Description
AUC0-t The area under the plasma concentration-time curve, from time 0 (time of dosing) to the last time point with measurable analyte concentration, calculated by the log down, linear up trapezoidal method.
AE Adverse Event ATC Anatomical Therapeutic Class
AUC0-inf The area under the plasma concentration-time curve from time 0 extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant (kel).
AUC0-8 The area under the plasma concentration-time curve, from time 0 (time of dosing) to the 8 hours concentration, calculated by the log down, linear up trapezoidal method.
BLQ Below the quantitation limit
CAP Community-Acquired Pneumonia CBC Complete Blood Count
Cmax Maximum observed concentration Cmin Minimum observed concentration over the dosing interval.
CL/F Apparent clearance calculated as Dose/AUC0-inf.
CS Clinically Significant CSR Clinical Study Report
CV Coefficient of variation DLT Dose Limiting Toxicity
DN_AUC0-inf Dose-normalized AUC0-inf, calculated as AUC0-inf divided by dose. DN_AUC0-t Dose-normalized AUC0-t, calculated as AUC0-t divided by dose.
DN_AUC0-8 Dose-normalized AUC0-8, calculated as AUC0-8 divided by dose.
DN_Cmax Dose-normalized Cmax, calculated as Cmax divided by dose.
EKG Electrocardiogram eCRF Electronic Case Report Form
EOS End of Study GCP Good Clinical Practice
geo CV Geometric Coefficient of Variation HIV Human Immunodeficiency Virus
ITT Intention-to-treat
IV Intravenous IWRS Interactive web response system
kel Apparent terminal elimination rate constant, calculated by linear regression of the terminal linear portion of the log concentration vs. time curve.
LLQ Lower Limit of Quantification MAD Multiple-Ascending Dose
MedDRA Medical Dictionary for Regulatory Activities MMSE Mini-Mental State Exam
N/A Not Applicable
NCS Not Clinically Significant
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Abbreviation Description
NK Not Known
PE Physical Examination
PI Principal Investigator PK Pharmacokinetic
PP Per Protocol PSI Pneumonia Severity Index
PT Preferred Term rhu-pGSN Recombinant human plasma Gelsolin
SAE Serious Adverse Event
SAP Statistical Analysis Plan SD Single Dose
SD* Standard Deviation S.I. International System of Units
SOC* Standard of Care
SOC System Organ Class SOP Standard Operating Procedure
t½ Apparent elimination half-life, calculated as ln(2)/kel. TEAE Treatment Emergent Adverse Event
Tmax Time to maximum observed drug concentration. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value.
Vz/F Apparent volume of distribution at the terminal phase, calculated as Dose/ (kel × AUC0-inf).
WHO-DD World Health Organization Drug Dictionary
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1. INTRODUCTION
The following Statistical Analysis Plan (SAP) provides the outline for the statistical analysis of the data from the BT-201 study. The planned analyses identified in this SAP may be included in clinical study reports (CSRs), regulatory submissions, or future manuscripts. Also, post hoc exploratory analyses not necessarily identified in this SAP may be performed to further examine study data. Any post hoc, or unplanned, exploratory analyses performed will be clearly identified as such in the final CSR.
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2. PROJECT OVERVIEW
2.1 Study Design
Study BTI-201 is a Phase 1b/2a, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of recombinant human plasma gelsolin (rhu-pGSN) added to standard of care (SOC*) in subjects hospitalized for acute community-acquired pneumonia (CAP). Each dosing cohort will include 8 subjects randomized 3:1 rhu-pGSN:placebo (6 rhu-pGSN subjects:2 placebo subjects).
There will be 1 single dose cohort (Cohort 1) and 3 multiple dose cohorts (Cohorts 2, 3 and 4).
Dose will be based on actual body weight. Dose escalation will involve 3 dose levels of rhu-pGSN (6, 12, and 24 mg/kg) in patients admitted for CAP. Dose escalation will only occur after post-therapy safety information on all subjects in the prior cohort has been reviewed at Day 7 for the single-dose (SD) and multiple-ascending dose (MAD*) arms.
The MAD portion of the study will commence once single doses of 6 mg/kg of rhu-pGSN are shown to be acceptably safe. The first 2 doses must be administered in the hospital, but the third dose can be given in a monitored outpatient setting where appropriate.
Discharged subjects will return for follow-up 7 days after the initiation of therapy (Day 7) and on Day 28 for the End-of-Study (EOS) Visit.
To assess safety and tolerability, subjects will undergo physical examinations (PE; including vital sign measurements), AE assessments, concomitant medication assessments, safety laboratory testing and Electrocardiogram (EKGs - completed locally), and other testing as per local custom.
2.2 Objectives
2.2.1 Primary objective
The primary objective of the study will be to evaluate the safety and tolerability of single and multiple ascending doses of rhu-pGSN administered by once-daily intravenous (IV) push to hospitalized subjects with a primary admitting diagnosis of CAP.
2.2.2 Secondary objectives
The secondary objective of the study will be to characterize the PK profile of rhu-pGSN after single or multiple IV doses
2.2.3 Exploratory objective.
The exploratory objectives of the study will be to investigate the following:
To assess the quantitative relationship of pGSN levels at baseline with clinical outcomes, changes in prognostic indices and inflammatory biomarkers, and etiologic pathogen type.
To assess the relationship between rhu-pGSN dose and clinical response and changes in surrogate biomarkers of efficacy.
2.2.4 Immunogenicity objective.
The immunogenicity objective of the study will be to investigate the post-treatment development of antibodies against rhu-pGSN by Day 28.
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2.3 Sample Size
The sample size of N=6 rhu-pGSN recipients per dose level and combined placebo in the SD and MAD portions of the trial were chosen based on limiting exposure to pGSN in this initial study in the current development program. The sample sizes in this trial have the following properties in relation to interpretation of Adverse Events (AEs) incidence rates (Table 1).
Table 1 presents the Minimum Sample Size such that there is 90% probability of observing at least 1 AE of a certain type if the TRUE underlying AE rate.
Table 1: Minimum Sample Size Calculations
Sample Size TRUE underlying AE rate
6 (each pGSN dose level) 32% 8 (pooled placebo) 21% 24 (pooled pGSN) 10%
With each sample size presented in the table above, if zero AEs of a certain type are observed, one could be "90% confident" the TRUE underlying rate for that AE is at most the rate indicated above.
2.4 Randomization
Following screening, subjects qualified for study entry will be randomized to receive rhu-pGSN or placebo during the treatment period. Randomization will be done centrally using the Interactive web response system (IWRS). All eligible subjects will be assigned a randomization number.
There will be 1 single dose cohort (Cohort 1) and 3 multiple dose cohorts (Cohorts 2, 3 and 4). Eight subjects will be sequentially randomized to each cohort for a total number randomized of 32 subjects.
Subjects will be randomized in a 3:1 ratio to rhu-pGSN or placebo (6 rhu-pGSN subjects:2 placebo subjects).
The investigational site team and the subject will be kept blinded to the treatment allocation of each participant. Only the designated pharmacist(s) will be unblinded to the treatment allocation. The unblinded pharmacist will utilize the IWRS system to randomly assign a treatment allocation. The treatment allocation will be available to the unblinded pharmacist(s).
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3. STATISTICAL CONSIDERATIONS
Data will be handled and processed per the sponsor’s representative (Novotech) Standard Operating Procedures (SOPs), which are written based on the principles of good clinical practice (GCP).
All data collected on the eCRFs will be presented in the data listings and will be listed and sorted by SD/MAD, treatment, subject number and visit, where applicable. All summaries will present the data by SD/MAD (apart from PK summaries), treatment group and overall (total subjects), as applicable. In addition, all placebo subjects will be combined into a single placebo group for purposes of summarizing the data.
Continuous variables: Descriptive statistics will include the number of non-missing values (N), mean, standard deviation (SD*), median, minimum, maximum.
The minimum and maximum values will be displayed to the same decimal precision as the source data, the arithmetic mean, SD* and median values will be displayed to one more decimal than the source data for the specific variable.
The appropriate precision for derived variables will be determined based on the precision of the data on which the derivations are based, and statistics will be presented in accordance with the abovementioned rules.
PK data: For PK data the arithmetic mean, standard deviation, median, minimum, maximum, coefficient of variation (CV%), geometric mean and geometric coefficient of variation (geo CV%) values will be presented. For the ratio of concentration data to the (within 30 minutes) pre-dose concentration on Day 1, the ln(SD*) will also be presented.
Categorical variables: Descriptive statistics will include frequency counts and percentages per category. Percentages will be rounded to one decimal place, with the denominator being the number of subjects in the relevant population with non-missing data, unless otherwise specified.
Time to Event Analysis: Through the Kaplan-Meier method, nonparametric estimates of the survivor function will be represented by quartile estimates (Q1, Median and Q3) along with 95 CIs. Product limit estimates will be presented as part of appendices to the study outputs (SAS output).
Imputation: No missing data will be imputed.
Baseline: Baseline values will be defined as the last valid, non-missing observation for each subject prior to the first dose of study medication. For the PK analysis, baseline will be defined as the pre-dose value for each study day.
Repeat assessments (Safety): No repeat assessments will be included in summary presentations (Tables, Figures). Only the original values will be used in summary presentations. All repeat assessments captured in the Electronic Data Capture (EDC) system will be presented in the data listings.
Assessment windows: All assessments will be included in the data listings and no visit windows will be applied to exclude assessments that were performed outside of the protocol specified procedure windows.
Date and time display conventions: The following display conventions will be applied in all outputs where dates and/or times are displayed:
Date only: DDMMMYYYY
Date and time: DDMMMYYYY /HH:MM
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If only partial information is available, unknown components of the date or time will be presented as ‘NK’ (not known), i.e., ‘2016-NK-NK’. Times will be reported in military time.
In the summary tables and figures, treatment groups will be summarized separately for SD/MAD, each cohort, combined placebo and overall (all subjects). Study outcomes will be summarized as follows:
For each active dose level (overall):
SD Phase:
rhu-pGSN 6 mg/kg
Placebo
Overall
MAD Phase
rhu-pGSN 6 mg/kg
rhu-pGSN 12 mg/kg
rhu-pGSN 24 mg/kg
Combined Active
Combined Placebo
Overall
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4. ANALYSIS POPULATIONS
In this study, four analysis populations are defined: Intention-to-treat (ITT), Safety, Pharmacokinetic and the Per Protocol populations (PP).
Furthermore, any additional exploratory analysis not identified in the SAP will be identified in the final CSR as exploratory post hoc analyses. This may include the addition of additional study populations or subgroups of interest.
The number and percentage of subjects in each analysis population will be summarized.
4.1 Population Descriptions
4.1.1 Intention-to-treat (ITT) population
The ITT population will be defined as all randomized subjects. Subjects will be analyzed per the randomized treatment they received if different from the actual treatment received.
All disposition, demographic and pharmacodynamic (PD) analyses will be based on the ITT population. All listings will be presented by the ITT population.
4.1.2 Safety population
The safety population will be defined as all enrolled subjects who received at least one dose of the study drug and will be based on actual treatment received.
If the safety population differs from the ITT population in that subjects received a different treatment to that they were randomized, or did not receive treatment whatsoever after randomization, the demographic and pharmacodynamic analyses will be repeated for the safety population.
All safety analyses will be based on the safety population.
4.1.3 Pharmacokinetic (PK) population
The PK population will comprise all subjects in the safety population who provide adequate PK samples to calculate the PK parameters. Subjects with important protocol deviations will be assessed on a subject-by-subject basis for inclusion in the PK Population. The PK analysis will be conducted using the Pharmacokinetic population.
4.1.4 Per Protocol (PP) population
The PP population will comprise all subjects in the safety population excluding subjects who missed doses and/or randomly discontinued the study before the primary Day 7 Visit. Furthermore, subject that had any relevant important protocol deviations will be excluded from the PP population.
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5. PROTOCOL DEVIATIONS
In case protocol deviations/violations are reported, all protocol deviations/violations will be listed for each subject in the by-subject data listings. Prior to database lock and during the blinded review of database, all protocol deviations/violations will be reviewed and assigned a status of important or not.
Important protocol deviations/violations may include the following, depending on the timing and nature of the deviation:
INFORMED CONSENT DEVIATION: Subject not consented prior to study procedures being performed or subject not re-consented to study at next scheduled study visit following local approval of an updated PIS-CF.
ENTRY DEVIATION: Subject enrolled in violation of eligibility criteria.
WITHDRAWAL DEVIATION: Subject developed withdrawal criteria during the study, but were not withdrawn.
DOSING DEVIATION: Subject received the wrong treatment or incorrect dose of investigational product or comparator; Subject received treatment at incorrect timepoint in study; Subject received treatment that had not been stored per protocol.
OPERATIONAL DEVIATION: Informed consent deviations (other than consent not being obtained prior to study entry, which would be considered an Entry Deviation), IRB/IEC expired approval, significant visit window deviations, or other issues that may significantly impact subject safety or data integrity.
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6. SUBJECT DISPOSITION
Outcomes will be summarized by the treatment groups as specified in section 3.
6.1.1 Subject disposition
Subject disposition will be summarized using counts and percentages and will be based on the ITT Population. The number of screened subjects, number and percentage of randomized subjects, subjects discontinued from the study as well as the primary reason for discontinuation will also be summarized.
All disposition information collected will be listed together with the date that the subject provided informed consent and the date and time of the first study drug administration. If the there is a difference between the ITT, Safety populations or the PP population, the disposition summary tables will be repeated for that population.
6.1.2 Analysis Populations
The number of subjects included in of each of the defined analysis populations will be summarized using counts and percentages and will be based on the ITT Population.
In addition, the inclusion/exclusion of each subject into/from each of the defined analysis populations will be listed.
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7. DEMOGRAPHIC AND BASELINE INFORMATION
Demographic and baseline body measurements will be summarized using the ITT Population and may be repeated for the safety population and per protocol populations if different from the ITT population.
All information will be presented by the treatment groups as specified in section 3.
7.1 Demographics
7.1.1 Definition of variables
Age (years);
Sex;
Child Bearing Potential;
Method of Birth Control;
Race;
Height (cm);
Weight (kg);
7.1.2 Biostatistical methods
Quantitative and categorical summaries will be presented for demographic variables at the screening visit.
A by-subject data listing for demographic and baseline characteristics will be generated.
7.2 Medical history
Past medical history will be coded using the Medical Dictionary for Regulatory Activities, (MedDRA - latest version), and will be presented in the by-subject data listings including the MedDRA codes.
7.3 Pregnancy Test (Serum and Urine)
Pregnancy test results will be included in the by-subject data listings. This includes the pregnancy test results at Screening and Day 28/End of Study.
7.4 Serology
The following viral detection results (serologies) at Screening will be listed for each subject when available: Hepatitis B, Hepatitis C and HIV status.
7.5 Other baseline characteristics
Confirmation of CAP (both clinical and radiographic) will be presented in the by-subject data listings.
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8. STUDY DRUG ADMINISTRATION
Study drug administration results will be presented using the ITT Population.
A by-subject data listing will be generated for study medication administration. These listings will include randomized dose assignment, Date/Time of Injection, Study Drug Administered (mL), duration of administrations, reason whole study drug dose was not administered, injection interruptions, re-start and reason for any interruptions. Subjects who receive the wrong IP (rhu-pGSN vs. placebo) will be flagged.
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9. PHARMACOKINETICS (PK)
All PK summary tables and figures will be based on the PK Population. All listings will be based on the Safety Population (Actual Treatment). All analyses will be done by treatment group.
For the 1 dose in the SD arm and the first 2 doses in the MAD arms, blood will be drawn within 30 minutes pre-dose, and 5-10 minutes after the end of administration, as well as 2, 8, 12 and/or 16, and 24 hours after the end of administration (± 30 minutes) for analysis. Identical PK sampling is encouraged on Day 3 where feasible (but not required) in the multiple-dose arms.
In this section (section 9):
The rhu-pGSN treatment group will be referred to the Active treatment group.
Exogenous pGSN concentrations will be referred to as rhu-pGSN concentrations.
Endogenous pGSN + Exogenous pGSN (total) will be referred to as pGSN
9.1 Definition of variables
The following PK parameters for pGSN will be estimated For Day 1(SD/MAD), Day 2 (MAD) and Day 3 (MAD). PK Parameters will only be calculated for the Active (rhu-pGSN) treatment group. No PK parameters will be calculated for the Placebo treatment group:
Day 1: SD/MAD & Day 2/3: MAD
AUC0-t The area under the plasma concentration-time curve, from time 0 (time of dosing) to the last time point (24 hours) with measurable analyte concentration, calculated by the log down, linear up trapezoidal method.
AUC0-t will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.
AUC0-8 The area under the plasma concentration-time curve, from time 0 (time of dosing) to the 8 hours concentration, calculated by the log down, linear up trapezoidal method.
AUC0-8 will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.
AUC0-inf The area under the plasma concentration-time curve from time 0 extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant (kel).
Cmax Maximum observed concentration.
Cmax will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.
Tmax Time to maximum observed drug concentration. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value.
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kel Apparent terminal elimination rate constant calculated by linear regression of the terminal linear portion of the log concentration vs. time curve.
t½ Apparent elimination half-life, calculated as ln(2)/kel
%AUCext Percentage of the extrapolated area under the plasma concentration-time curve, calculated as 100% * [AUC0-inf - AUC0-t]/ AUC0-inf
CL/F Apparent clearance calculated as Dose/AUC0-inf.
Vz/F Apparent volume of distribution at the terminal phase, calculated as Dose/ (kel × AUC0-inf).
DN_Cmax Dose-normalized Cmax, calculated as Cmax divided by dose
DN_Cmax will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose day 1 and the double-delta method..
DN_AUC0-inf Dose-normalized AUC0-inf, calculated as AUC0-inf divided by dose
DN_AUC0-t Dose-normalized AUC0-t, calculated as AUC0-t divided by dose
DN_AUC0-t will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.
DN_AUC0-8 Dose-normalized AUC0-24, calculated as AUC0-24 divided by dose
DN_AUC0-8 will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.
9.2 Biostatistical methods
Plasma pGSN
Individual plasma pGSN concentrations will be summarized by nominal sampling time.
Plasma pGSN concentrations that are below the quantitation limit (BQL) will be set to 0 if before the first quantifiable concentration, and to ½ the lower level of quantification elsewhere for calculation of summary statistics for concentration data at each time point.
The actual blood sampling dates and times relative to dosing time will be listed by subject and nominal sampling time, with time deviations calculated for all subjects with available plasma concentration data, including subjects excluded from the PK Population.
Individual (for each subject) and mean plasma pGSN concentration over time will be displayed graphically in linear and semi-logarithmic plot of pGSN concentration versus time. The actual collection time will be used for individual plasma pGSN concentration curve and the nominal time will be used for plot of mean plasma pGSN concentration curve.
Plasma concentrations vs. time data will be analyzed using validated PK software (Phoenix WinNonlin version 6.3 or higher), by standard non-compartmental model. Actual collection time will be used in the calculation of plasma PK parameters. For the calculation of the PK parameters, all plasma concentrations that are BLQ prior to the first measurable
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concentration will be set to ½ the lower level of quantification. The BLQ values that are between measurable concentrations will be set to ½ LLOQ. The BLQ values that occur at the end of the profile (after the last quantifiable concentration) will also be set to ½ the lower level of quantification.
Ratio of Plasma pGSN
For subjects that do not have quantifiable pre-dose concentration values on each day, the pre-dose value will be set to ½ lower limit of quantification (LLQ).
Individual plasma pGSN: Day 1, 2 and Day 3 pGSN concentration ratios from each day’s pre-dose will be summarized by nominal sampling time.
Plasma pGSN concentrations that are below the quantitation limit (BQL) will be set to ½ the lower level of quantification post dose for calculation of summary statistics for concentration ratio data at each time point.
Ratio of Pre-dose and Placebo Adjusted Plasma pGSN
For the active treatment groups, plasma concentration of pGSN will further be evaluated (adjusted) in terms of the mean Placebo pGSN at each time point as well as the pre-dose (baseline value) for each study day:
Pre-dose values on each study day will be presented as recorded;
Pre-dose values on each study day that are BLQ will be set to ½ LLQ;
Subsequent BLQ values (post the first quantifiable concentration on each day) will be set to ½ LLQ.
Pre-dose and Placebo Adjusted Concentration
= (Active Treatment Group natural log Concentration on Day z at Time Point y – Day z Pre-dose natural log Concentration) - (Placebo Treatment Group natural log Concentration on Day z at Time Point y – Placebo Day z Pre-dose natural log Concentration) [results will be back-transformed to the ratio of ratios scale.]
Baseline and Placebo corrected Individual plasma pGSN concentrations will be summarized by nominal sampling time.
Analysis of Estimated rhu-pGSN
This analysis will exclude the placebo treatment group:
Pre-dose values on each study day will be presented as recorded;
Pre-dose values on each study day that are BLQ will be set to ½ LLQ;
Subsequent BLQ values (post the first quantifiable concentration on each day) will be set to ½ LLQ.
Estimated rhu-pGSN concentration
= concentration on Day z at Time Point y – Day z Pre-dose concentration
Individual estimated rhu-pGSN concentrations will be summarized by nominal sampling time. Geometric summary statistics will not be calculated for estimated rhu-pGSN concentrations, as these values could be lower than or equal to 0.
Estimated Individual (for each subject) and mean estimated plasma rhu-pGSN concentration over time will be displayed graphically in linear plots of estimated rhu-pGSN concentration versus time. The actual collection time will be used for individual estimated plasma rhu-pGSN concentration curve and the nominal time will be used for plot of mean estimated plasma rhu-pGSN concentration curve.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 21 of 44
Estimated plasma concentrations vs. time data will be analyzed using SAS software. Actual collection time will be used in the calculation of plasma PK parameters. The following parameters (including dose normalized parameters) will be calculated for each study day:
AUC0-t
AUC0-8h
Cmax
Double Delta Analysis of Estimated rhu-pGSN
Pre-dose values on each study day will be presented as recorded;
Pre-dose values on each study day that are BLQ will be set to ½ LLQ;
Subsequent BLQ values (post the first quantifiable concentration on each day) will be set to ½ LLQ.
Estimated rhu-pGSN will be calculated as follows:
= (Active Treatment Group Concentration on Day z at Time Point y – Day z Pre-dose Concentration) - (Mean Placebo Treatment Group Concentration on Day z at Time Point y – Mean Placebo Day z Pre-dose Concentration)
Estimated rhu-pGSN concentrations will be summarized by nominal sampling time. Geometric summary statistics will not be calculated for estimated rhu-pGSN concentrations, as these values could be lower than or equal to 0.
Estimated Individual (for each subject) and mean estimated plasma rhu-pGSN concentration over time will be displayed graphically in linear plots of estimated rhu-pGSN concentration versus time. The nominal time will be used for individual estimated plasma rhu-pGSN concentration curve and the nominal time will be used for plot of mean estimated plasma rhu-pGSN concentration curve.
Estimated rhu-pGSN plasma concentrations vs. time data will be analyzed using SAS software. Nominal time will be used in the calculation of plasma PK parameters. The following parameters (including dose normalized parameters) will be calculated for each study day:
AUC0-t
AUC0-8h
Cmax
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 22 of 44
10. PHARMACODYNAMICS (EFFICACY)
All PD summary tables, figures and listings will be based on the ITT Population. All analysis will be done by study part (SD/MAD) by each treatment group.
As a sensitivity analysis, the analysis will be repeated based on the PP population.
10.1 Definition of variables
The following biomarkers will be analyzed:
Procalcitonin;
pGSN;
TNFα;
TGFβ;
IL1β;
IL1ra;
IL2;
IL4;
IL6;
IL10;
IL17a.`
10.2 Biostatistical methods
Biomarker will be summarized via counts and percentages of subjects for categorical variables, and by summary statistics for baseline, each observed time point, and ratio from baseline at each observed time point for continuous variables (as for the PK analysis with the exception of CV% and Geometric CV%) by treatment group and overall.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 23 of 44
11. SAFETY
Safety endpoints will be analyzed using the Safety Population. All information will be presented by study part, for each treatment group and overall.
11.1 Adverse Events
11.1.1 Definition of variables
Adverse event (AE)
Serious adverse event (SAE)
Treatment emergent adverse event (TEAE)
AEs and SAEs are defined in the study protocol. TEAEs are defined as adverse events that occurred or worsened following the first administration of study medication. Adverse events that have missing onset dates will be considered treatment-emergent, unless the stop date is known to be prior to the first administration of the study medication.
11.1.2 Biostatistical methods
All AEs will be coded using MedDRA.
All AE summaries will be restricted to TEAEs only. Summary tables will include the number of subjects (%) experiencing an event and the number of events. Subjects will be counted only once at each system organ class (SOC) and preferred term (PT) level of summary.
The TEAE summaries will include:
TEAE summary by SOC and PT
TEAE summary of serious events by SOC and PT
TEAE summary of deaths by SOC and PT
TEAE summary by severity (NCI-CTCAE) by SOC and PT
TEAE summary by causality to Study Drug by SOC and PT
TEAE summary by causality to Study Procedure by SOC and PT
TEAE summary of events leading to treatment discontinuation (Drug withdrawn) by SOC and PT
All AEs will be listed and will include verbatim term, PT, SOC, treatment, severity, causality, seriousness, and action taken with regards to the study drug. Separate listings will be created for SAEs, deaths and events leading to treatment discontinuation (Drug withdrawn).
Overall survival (time to death in days) will be analyzed through Kaplan-Meier methods and censored at the time of the study exit visit. Date of death will be taken as the SAE end date for which the outcome is stated to be fatal. Overall survival (days) = Date of event outcome of death/ Date of study exit - Date of first study drug administration + 1.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 24 of 44
11.2 Safety Laboratory Assessments
Blood samples will be collected at the time points specified in the Schedule of Events (refer to the Protocol) to conduct Complete blood count (CBC), Coagulation and Comprehensive Metabolic Profile analyses.
11.2.1 Definition of variables
The following tests will be performed within each of the specified test panels:
Complete blood count (CBC):
Hematocrit (HCT);
Hemoglobin (HGB);
Red Blood Cells (RBC)
White Blood Cells (WBC) with differential (including Eosinophils (EOS), Neutrophils (NEUT), Basophils (BASO), Lymphocytes (LYM) and Monocytes (MONO);
Platelets (PLAT);
Reticulocyte count
Coagulation:
Prothrombin Time (PT) / International Normalized Ratio (INR);
Partial Thromboplastin Time (PTT).
Comprehensive Metabolic Profile:
Albumin (ALB)
Blood Urea Nitrogen (BUN)
Creatinine (CREAT)
C-Reactive Protein (CRP)
Lactate Dehydrogenase (LDH)
Creatine phosphokinase (CPK)
Alanine Aminotransferase (ALT)
Aspartate Aminotransferase (AST)
Total Bilirubin (BILI)
Alkaline Phosphatase (ALP)
Amylase
Lipase
11.2.2 Biostatistical Methods
All laboratory data collected at scheduled and unscheduled visits will be included in the listings, but only results collected as scheduled visits will be included in the summary tables.
Results for individual parameters may be reported in different units depending on the analyzing laboratory. If required, the results (and the corresponding normal range cut-off values) for individual parameters may be converted to International System of Units (S.I.) units to summarize the data.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 25 of 44
For the all parameters where a unit value has been reported, the parameter names that will be used in the outputs will comprise of the test name and the unit of measure, for example, ‘Albumin (g/L)’. Parameters will be sorted alphabetically within tables and listings.
For all parameters where a normal range limit value is reported, the normal range will be derived based on the available lower and upper limit values and any reported mathematical symbols. If both a lower and upper limit value is available, the normal range will be presented as ‘(Lower, Upper)’.
The reported results for each parameter with a defined normal range will be classified (‘Low’, ‘Normal’, ‘High’) in relation to the defined normal range limits. If a result is equal to the normal range cut-off value, the result will be considered ‘Normal’.
The change from baseline values at each post-baseline visit will be calculated for all parameters with continuous results (except for specific gravity and pH).
The decimal precision for each parameter will be based on the maximum number of decimals to which the reported result or the normal range limits are presented to in the raw data. The results and normal ranges will be displayed to the same decimal precision in the listings.
If a result for a parameter that is normally considered continuous is reported as a range (i.e., the result for basophils is reported as ‘<0.01’ for a single time point), the result may be converted to a numeric value that is smaller than the reported result to contribute to the derivations and the summary statistics. Any conversion rules that are applied will be highlighted in the footnotes of the affected tables and listings. The original reported result value will however be included in the listing.
The laboratory result tables will present summary statistics for each laboratory parameter within the specific test panel. For each parameter, summaries will be presented for the baseline and each scheduled post-baseline visit. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit.
Additionally, counts (%) of number subjects with values out of normal range at each scheduled time point will also be presented along with shift tables that will represent the changes in normal range categories across post-baseline time points.
The listings of laboratory parameters will include all the information (fields) collected. In addition, the observations that are used as the baseline record (value) for each parameter will be flagged, and the change from baseline values at each post-baseline visit will be presented.
For all parameters, standardized values will be reported.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 26 of 44
11.3 Vital Signs Measurements
11.3.1 Definition of variables
The following vital signs measurements will be taken at the time points specified in the Schedule of Events (refer to the Protocol):
Heart Rate (beats/min);
Systolic blood pressure (SBP) (mmHg)
Diastolic blood pressure (DBP) (mmHg)
Respiratory rate (breaths/min)
Temperature (ºC)
Pulse Oximetry (%)
Overall Investigator Interpretation
11.3.2 Biostatistical Methods
All vital signs data collected at scheduled and unscheduled visits will be included in the listings, but only results collected as scheduled visits will be included in the summary tables.
The parameter names that will be used in the outputs will comprise of the test name and the unit of measure, for example, ‘Systolic Blood Pressure (mmHg)’. Parameters will be sorted in the order that the measurements were collected in on the Vital Signs eCRF page within the tables and listings.
The change from baseline to the pre-dose assessment at each post-baseline visit will be calculated for all parameters.
The decimal precision for each parameter will be based on the maximum number of decimals to which the results were reported on the eCRF.
Vital signs measurements will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit.
The summary of overall interpretation results table will present counts and percentages for the reported results at baseline and each post-baseline visit/time point. Result categories will be ordered as ‘Normal’, ‘Abnormal not clinical significant (NCS)’ and ‘Abnormal clinical significant (CS)’.
The listings of vital signs measurements will include all the information collected. In addition, the observations that are used as the baseline record (value) for each parameter will be flagged, and the change from baseline values at each post-baseline visit will be presented.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 27 of 44
11.4 12 - Lead Electrocardiogram (EKG)
11.4.1 Definition of variables
The following EKG measurements will be taken at the time points specified in the Schedule of Events (refer to the Protocol):
Heart Rate (beats/min);
PR Interval (ms)
QRS Interval (ms)
QT Interval (sec)
QTcF Interval (ms) = QT interval /cube root of the RR interval
Overall Investigator Interpretation
11.4.2 Biostatistical Methods
All EKG data collected at scheduled and unscheduled visits will be included in the listings, but only results collected as scheduled visits will be included in the summary tables.
The parameter names that will be used in the outputs will comprise of the test name and the unit of measure, for example, ‘Heart Rate (beats/min)’. Parameters will be sorted in the order that the measurements were collected in on the EKG eCRF page within the tables and listings.
For study visits where, multiple EKG measurement are taken, the mean of the measurements will be summarized and the worst-case overall investigator interpretation for the multiple measurements will be presented.
The change from baseline to the pre-dose assessment at each post-baseline visit will be calculated for all parameters.
The decimal precision for each parameter will be based on the maximum number of decimals to which the results were reported on the eCRF.
EKG measurements will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit.
The summary of overall interpretation results table will present counts and percentages for the reported results at baseline and each post-baseline visit/time point. Result categories will be ordered as ‘Normal’, ‘Abnormal NCS’ and ‘Abnormal CS’.
The listings of EKG measurements will include all the information collected and calculated (mean results). In addition, the observations that are used as the baseline record (value) for each parameter will be flagged, and the change from baseline values at each post-baseline visit will be presented.
11.5 Physical Examinations
Physical Examination assessments will be listed for all time points.
11.6 Outcome Prediction Models
11.6.1 Definition of variables
The following outcome prediction models will be taken at the time points specified in the Schedule of Events (refer to the Protocol):
CURB-65 Score;
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 28 of 44
Pneumonia Severity Index (PSI) Score
Pneumonia Severity Index (PSI) Risk Class
SOFA Score
Mini-Mental State Exam (MMSE) Score
11.6.2 Biostatistical Methods
All outcome prediction model data collected at scheduled and unscheduled visits will be included in the listings, but only results collected as scheduled visits will be included in the summary tables.
The change from baseline to the pre-dose assessment at each post-baseline visit will be calculated for all parameters.
The decimal precision for each parameter will be based on the maximum number of decimals to which the results were reported on the eCRF.
Outcome prediction model scores will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit.
The summary of PSI Risk Class will present counts and percentages for the reported results at baseline and each post-baseline visit/time point. Result categories will be ordered by risk class.
The listings of outcome prediction model data will include all the information collected. In addition, the observations that are used as the baseline record (value) for each parameter will be flagged, and the change from baseline values at each post-baseline visit will be presented.
11.7 Concomitant Medications
Concomitant and prior medications will be coded using World Health Organization Drug Dictionary (WHO-DD, September 2015).
Prior medications are defined as any medication where the use was stopped prior to the first administration of the study medication. Prior medications will be listed only.
Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration of the study medication. Medications that were stopped on the same date as the first study drug infusion will be analyzed as concomitant medications. If a clear determination cannot be made (partial medication end dates) the medication will be classified as concomitant.
Concomitant medications will be summarized by WHO-DD Anatomical Therapeutic Chemical (ATC) class Level 3, and preferred term using frequency counts and percentages by study part and treatment group. Subjects who take the same medication more than once will be counted only once for that preferred term. Subjects will also only be counted once for each ATC3 class, regardless of the number of medications they have taken within that class
11.8 Other safety evaluations
Hospitalization follow-up will be presented in by-subject listings by study part and treatment group. Length of stay in hospital defined as date and time of discharge or date of study exit if still hospitalized at the time of death or study exit (censored at 23:59) - date and time of Hospitalization admission due to CAP in hours, length of ICU stay and the period of intubation in days will be listed and presented through Kaplan-Meier (K-M) methods.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 29 of 44
The length of stay in ICU and period of intubation analysis will be restricted to subjects that stayed in the ICU and were intubated. The event investigated will be the cessation of ICU stay and the cessation of intubation.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 30 of 44
12. IMMUNOGENICITY ENDPOINTS
All Immunogenicity endpoints will be listed using the safety population by study part and treatment. Specimens from placebo recipients will serve as a negative control.
Antibodies against rhu-pGSN will be blindly assayed from frozen specimens to determine whether the investigational product induces an antibody response in recipients.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 31 of 44
13. EXPLORATORY ENDPOINTS
Other analyses to be performed include:
Blood, sputum, and other cultures as clinically indicated (note that a sputum culture is mandatory if a sputum specimen can be obtained and blood cultures are strongly encouraged at entry into the study).
Sputum neutrophil elastase (where feasible at entry and near the conclusion of study therapy).
Exploratory endpoints will be listed only.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 32 of 44
14. HANDLING OF MISSING DATA
Missing, unused, or spurious data will be handling in the following manner:
There will be no imputations or substitution made for missing PD or safety data points;
For the PK analyses, imputations will be made for missing data points. Please see section 9 for more detail.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 33 of 44
15. CHANGES TO THE PLANNED ANALYSIS
No planned changes.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
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15.1 Final Analysis (End of Study)
The final analysis will be conducted after all subjects have completed the study, the clinical database has been locked and the analysis populations have been approved.
The final analysis will be based on the final version of the SAP. Any deviations from the planned analysis will be documented in the CSR.
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 35 of 44
16. SOFTWARE
The following software will be used to perform the statistical analyses:
SAS® Version 9.4 or higher (SAS Institute, Cary, North Carolina, USA).
The following software will be used to perform the PK analysis: Phoenix WinNonlin® version 6.3 or higher.
Pro
toco
l Num
ber:
BT
-201
03 D
ecem
ber
2018
D
ocum
ent s
tatu
s: F
inal
SA
P V
ersi
on 2
.0 A
men
dmen
t 1.0
N
ovot
ech
- S
tric
tly C
onfid
entia
l
Pag
e 36
of 4
4
17.
TA
BL
ES
No
. T
itle
A
na
lys
is
Po
pu
lati
on
14
.1.1
.1
SD
: Sum
mar
y of
Sub
ject
Enr
olm
ent a
nd D
ispo
sitio
n In
tent
-to-
Tre
at
14.1
.1.2
M
AD
: Sum
mar
y of
Sub
ject
Enr
olm
ent a
nd D
ispo
sitio
n In
tent
-to-
Tre
at
14.1
.2.1
S
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ary
of D
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raph
ics
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e C
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s In
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at
14.1
.2.2
M
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: Sum
mar
y of
Dem
ogra
phic
s an
d B
asel
ine
Cha
ract
eris
tics
Inte
nt-t
o-T
reat
14
.2.1
.1
Day
1: S
umm
ary
of P
lasm
a pG
SN
Con
cent
ratio
ns (
unit)
by
Tim
epoi
nt
PK
14
.2.1
.2
Day
2: S
umm
ary
of P
lasm
a pG
SN
Con
cent
ratio
ns (
unit)
by
Tim
epoi
nt
PK
14
.2.1
.3
Day
3: S
umm
ary
of P
lasm
a pG
SN
Con
cent
ratio
ns (
unit)
by
Tim
epoi
nt
PK
14
.2.1
.4
Day
1: S
umm
ary
of E
stim
ated
Pla
sma
rhu-
pGS
N C
once
ntra
tions
(un
it) b
y T
imep
oint
P
K
14.2
.1.5
D
ay 2
: Sum
mar
y of
Est
imat
ed P
lasm
a rh
u-pG
SN
Con
cent
ratio
ns (
unit)
by
Tim
epoi
nt
PK
14
.2.1
.6
Day
3: S
umm
ary
of E
stim
ated
Pla
sma
rhu-
pGS
N C
once
ntra
tions
(un
it) b
y T
imep
oint
P
K
14.2
.2.1
D
ay 1
: Sum
mar
y of
Pla
sma
pGS
N P
K P
aram
eter
s P
K
14.2
.2.2
D
ay 2
: Sum
mar
y of
Pla
sma
pGS
N P
K P
aram
eter
s P
K
14.2
.2.3
D
ay 3
: Sum
mar
y of
Pla
sma
pGS
N P
K P
aram
eter
s P
K
14.2
.3.1
D
ay 1
: Sum
mar
y of
Est
imat
ed P
lasm
a rh
u-pG
SN
PK
Par
amet
ers
PK
14
.2.3
.2
Day
2: S
umm
ary
of E
stim
ated
Pla
sma
rhu-
pGS
N P
K P
aram
eter
s P
K
14.2
.3.3
D
ay 3
: Sum
mar
y of
Est
imat
ed P
lasm
a rh
u-pG
SN
PK
Par
amet
ers
PK
14
.2.4
.1
SD
: Sum
mar
y of
PD
Par
amet
ers
Inte
nt-t
o-T
reat
14
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.2
MA
D: S
umm
ary
of P
D P
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tent
-to-
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at
14.2
.5.1
S
D: S
umm
ary
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D P
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M
AD
: Sum
mar
y of
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Par
amet
ers
Per
Pro
toco
l 14
.3.1
.1
SD
: Sum
mar
y of
Con
com
itant
Med
icat
ion
Saf
ety
14.3
.1.2
M
AD
: Sum
mar
y of
Prio
r and
Con
com
itant
Med
icat
ion
Saf
ety
14.3
.3.1
.1
SD
: Ove
rall
Sum
mar
y of
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s S
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y 14
.3.3
.1.2
M
AD
: Ove
rall
Sum
mar
y of
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s S
afet
y 14
.3.3
.2.1
S
D: S
umm
ary
of T
reat
men
t-E
mer
gent
Adv
erse
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nts
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mar
y by
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C, P
T)
Saf
ety
14.3
.3.2
.2
MA
D: S
umm
ary
of T
reat
men
t-E
mer
gent
Adv
erse
Eve
nts
(Sum
mar
y by
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C, P
T)
Saf
ety
14.3
.3.3
.1
SD
: Sum
mar
y of
Tre
atm
ent-
Em
erge
nt D
eath
s (S
umm
ary
by S
OC
, PT
) S
afet
y 14
.3.3
.3.2
M
AD
: Sum
mar
y of
Tre
atm
ent-
Em
erge
nt D
eath
s (S
umm
ary
by S
OC
, PT
) S
afet
y
Pro
toco
l Num
ber:
BT
-201
03 D
ecem
ber
2018
D
ocum
ent s
tatu
s: F
inal
SA
P V
ersi
on 2
.0 A
men
dmen
t 1.0
N
ovot
ech
- S
tric
tly C
onfid
entia
l
Pag
e 37
of 4
4
No
. T
itle
A
na
lys
is
Po
pu
lati
on
14.3
.3.4
.1
SD
: Sum
mar
y of
Ser
ious
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s (S
umm
ary
by S
OC
, PT
) S
afet
y 14
.3.3
.4.2
M
AD
: Sum
mar
y of
Ser
ious
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s (S
umm
ary
by S
OC
, PT
) S
afet
y 14
.3.3
.5.1
S
D: S
umm
ary
of T
reat
men
t-E
mer
gent
Adv
erse
Eve
nts
(Sum
mar
y by
SO
C, P
T a
nd N
CI-
CT
CA
E G
rade
) S
afet
y 14
.3.3
.5.2
M
AD
: Sum
mar
y of
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s (S
umm
ary
by S
OC
, PT
and
NC
I-C
TC
AE
Gra
de)
Saf
ety
14.3
.1.6
.1
SD
: Sum
mar
y of
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s (S
umm
ary
by S
OC
, PT
and
Rel
atio
nshi
p to
Stu
dy D
rug)
S
afet
y 14
.3.3
.6.2
M
AD
: Sum
mar
y of
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s (S
umm
ary
by S
OC
, PT
and
Rel
atio
nshi
p to
Stu
dy D
rug)
S
afet
y 14
.3.3
.7.1
S
D: S
umm
ary
of T
reat
men
t-E
mer
gent
Adv
erse
Eve
nts
(Sum
mar
y by
SO
C, P
T a
nd R
elat
ions
hip
to S
tudy
Pro
cedu
re)
Saf
ety
14.3
.3.7
.2
MA
D: S
umm
ary
of T
reat
men
t-E
mer
gent
Adv
erse
Eve
nts
(Sum
mar
y by
SO
C, P
T a
nd R
elat
ions
hip
to S
tudy
Pro
cedu
re)
Saf
ety
14.3
.3.8
.1
SD
: Sum
mar
y of
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s Le
adin
g to
Tre
atm
ent D
isco
ntin
uatio
n (S
umm
ary
by S
OC
, PT
) S
afet
y 14
.3.3
.8.2
M
AD
: Sum
mar
y of
Tre
atm
ent-
Em
erge
nt A
dver
se E
vent
s Le
adin
g to
Tre
atm
ent D
isco
ntin
uatio
n (S
umm
ary
by S
OC
, PT
) S
afet
y 14
.3.3
.9.1
S
D: S
umm
ary
of O
vera
ll S
urvi
val
Saf
ety
14.3
.3.9
.2
MA
D: S
umm
ary
of O
vera
ll S
urvi
val
Saf
ety
14.3
.4.1
.1.1
S
D: S
umm
ary
of C
BC
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.1.1
.2
MA
D: S
umm
ary
of C
BC
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.1.2
.1
SD
: Sum
mar
y of
CB
C S
hifts
from
Bas
elin
e (L
ow, N
orm
al, H
igh)
S
afet
y 14
.3.4
.1.2
.2
MA
D: S
umm
ary
of C
BC
Shi
fts fr
om B
asel
ine
(Low
, Nor
mal
, Hig
h)
Saf
ety
14.3
.4.2
.1.1
S
D: S
umm
ary
of C
oagu
latio
n (S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.2.1
.2
MA
D: S
umm
ary
of C
oagu
latio
n (S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.2.2
.1
SD
: Sum
mar
y of
Coa
gula
tion
Shi
fts fr
om B
asel
ine
(Low
, Nor
mal
, Hig
h)
Saf
ety
14.3
.4.2
.2.2
M
AD
: Sum
mar
y of
Coa
gula
tion
Shi
fts fr
om B
asel
ine
(Low
, Nor
mal
, Hig
h)
Saf
ety
14.3
.4.3
.1.1
S
D: S
umm
ary
of C
ompr
ehes
ive
Met
abol
ic P
rofil
e (S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.3.1
.2
MA
D: S
umm
ary
of C
ompr
ehes
ive
Met
abol
ic P
rofil
e (S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.3.2
.1
SD
: Sum
mar
y of
Com
preh
esiv
e M
etab
olic
Pro
file
Shi
fts fr
om B
asel
ine
(Low
, Nor
mal
, Hig
h)
Saf
ety
14.3
.4.3
.2.2
M
AD
: Sum
mar
y of
Com
preh
esiv
e M
etab
olic
Pro
file
Shi
fts fr
om B
asel
ine
(Low
, Nor
mal
, Hig
h)
Saf
ety
14.3
.4.4
.1
SD
: Sum
mar
y of
Vita
l Sig
ns (
Sum
mar
y of
Act
ual a
nd C
hang
e fr
om B
asel
ine
Val
ues)
by
Tim
epoi
nt
Saf
ety
14.3
.4.4
.2
MA
D: S
umm
ary
of V
ital S
igns
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.5.1
S
D: S
umm
ary
of V
ital S
igns
Inte
rpre
tatio
n by
Tim
epoi
nt
Saf
ety
14.3
.4.5
.2
MA
D: S
umm
ary
of V
ital S
igns
Inte
rpre
tatio
n by
Tim
epoi
nt
Saf
ety
14.3
.4.6
.1
SD
: Sum
mar
y of
Mea
n E
KG
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.6.2
M
AD
: Sum
mar
y of
Mea
n E
KG
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y
Pro
toco
l Num
ber:
BT
-201
03 D
ecem
ber
2018
D
ocum
ent s
tatu
s: F
inal
SA
P V
ersi
on 2
.0 A
men
dmen
t 1.0
N
ovot
ech
- S
tric
tly C
onfid
entia
l
Pag
e 38
of 4
4
No
. T
itle
A
na
lys
is
Po
pu
lati
on
14.3
.4.7
.1
SD
: Sum
mar
y of
EK
G In
terp
reta
tion
(Wor
st)
by T
imep
oint
S
afet
y 14
.3.4
.7.2
M
AD
: Sum
mar
y of
EK
G In
terp
reta
tion
(Wor
st)
by T
imep
oint
S
afet
y 14
.3.4
.8.1
S
D: S
umm
ary
of C
UR
B-6
5 S
core
(Sum
mar
y of
Act
ual a
nd C
hang
e fr
om B
asel
ine
Val
ues)
by
Tim
epoi
nt
Saf
ety
14.3
.4.8
.2
MA
D: S
umm
ary
of C
UR
B-6
5 S
core
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.9.1
S
D: S
umm
ary
of P
SI S
core
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.9.2
M
AD
: Sum
mar
y of
PS
I Sco
re (
Sum
mar
y of
Act
ual a
nd C
hang
e fr
om B
asel
ine
Val
ues)
by
Tim
epoi
nt
Saf
ety
14.3
.4.1
0.1
SD
: Sum
mar
y of
PS
I Ris
k C
lass
by
Tim
epoi
nt
Saf
ety
14.3
.4.1
0.2
MA
D: S
umm
ary
of P
SI R
isk
Cla
ss b
y T
imep
oint
S
afet
y 14
.3.4
.11.
1 S
D: S
umm
ary
of S
OF
A S
core
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.11.
2 M
AD
: Sum
mar
y of
SO
FA
Sco
re (
Sum
mar
y of
Act
ual a
nd C
hang
e fr
om B
asel
ine
Val
ues)
by
Tim
epoi
nt
Saf
ety
14.3
.4.1
2.1
SD
: Sum
mar
y of
MM
SE
Sco
re (
Sum
mar
y of
Act
ual a
nd C
hang
e fr
om B
asel
ine
Val
ues)
by
Tim
epoi
nt
Saf
ety
14.3
.4.1
2.2
MA
D: S
umm
ary
of M
MS
E S
core
(S
umm
ary
of A
ctua
l and
Cha
nge
from
Bas
elin
e V
alue
s) b
y T
imep
oint
S
afet
y 14
.3.4
.13.
1 S
D: S
umm
ary
of H
ospi
taliz
atio
n S
afet
y 14
.3.4
.13.
2 M
AD
: Sum
mar
y of
Hos
pita
lizat
ion
Saf
ety
Pro
toco
l Num
ber:
BT
-201
03 D
ecem
ber
2018
D
ocum
ent s
tatu
s: F
inal
SA
P V
ersi
on 2
.0 A
men
dmen
t 1.0
N
ovot
ech
- S
tric
tly C
onfid
entia
l
Pag
e 39
of 4
4
18.
LIS
TIN
GS
No
. T
itle
A
na
lys
is
Po
pu
lati
on
16
.2.1
.2.1
S
D: S
ubje
ct D
ispo
sitio
n In
tent
-to-
Tre
at
16.2
.1.2
.2
MA
D: S
ubje
ct D
ispo
sitio
n In
tent
-to-
Tre
at
16.2
.2.1
S
D: P
roto
col D
evia
tions
In
tent
-to-
Tre
at
16.2
.2.2
M
AD
: Pro
toco
l Dev
iatio
ns
Inte
nt-t
o-T
reat
16
.2.3
.1
SD
: Ana
lysi
s P
opul
atio
ns
Inte
nt-t
o-T
reat
16
.2.3
.2
MA
D: A
naly
sis
Pop
ulat
ions
In
tent
-to-
Tre
at
16.2
.4.1
.1
SD
: Dem
ogra
phic
s an
d B
asel
ine
Cha
ract
eris
tics
Inte
nt-t
o-T
reat
16
.2.4
.1.2
M
AD
: Dem
ogra
phic
s an
d B
asel
ine
Cha
ract
eris
tics
Inte
nt-t
o-T
reat
16
.2.4
.2.1
S
D: V
iral S
erol
ogy
Inte
nt-t
o-T
reat
16
.2.4
.2.2
M
AD
: Vira
l Ser
olog
y In
tent
-to-
Tre
at
16.2
.4.3
.1
SD
: Med
ical
His
tory
In
tent
-to-
Tre
at
16.2
.4.3
.2
MA
D: M
edic
al H
isto
ry
Inte
nt-t
o-T
reat
16
.2.4
.4.1
S
D: P
regn
ancy
Tes
t Res
ults
In
tent
-to-
Tre
at
16.2
.4.4
.2
MA
D: P
regn
ancy
Tes
t Res
ults
In
tent
-to-
Tre
at
16.2
.4.5
.1
SD
: Con
firm
atio
n of
CA
P
Inte
nt-t
o-T
reat
16
.2.4
.5.2
M
AD
: Con
firm
atio
n of
CA
P
Inte
nt-t
o-T
reat
16
.2.4
.6.1
S
D: E
ligib
ility
Ass
essm
ent
Inte
nt-t
o-T
reat
16
.2.4
.6.2
M
AD
: Elig
ibili
ty C
riter
ia
Inte
nt-t
o-T
reat
16
.2.4
.7.1
S
D: P
rior
Med
icat
ions
In
tent
-to-
Tre
at
16.2
.4.7
.2
MA
D: P
rior
Med
icat
ions
In
tent
-to-
Tre
at
16.2
.5.1
.1
SD
: Ran
dom
izat
ion
Inte
nt-t
o-T
reat
16
.2.5
.1.2
M
AD
: Ran
dom
izat
ion
Inte
nt-t
o-T
reat
16
.2.5
.2.1
S
D: S
tudy
Dru
g A
dmin
istr
atio
n In
tent
-to-
Tre
at
16.2
.5.2
.2
MA
D: S
tudy
Dru
g A
dmin
istr
atio
n In
tent
-to-
Tre
at
16.2
.5.3
.1
SD
: Stu
dy D
rug
Inte
rrup
tion
Inte
nt-t
o-T
reat
16
.2.5
.3.2
M
AD
: Stu
dy D
rug
Inte
rrup
tion
Inte
nt-t
o-T
reat
16
.2.6
.1.1
S
D: I
ndiv
idua
l pG
SN
Pla
sma
Con
cent
ratio
ns (
unit)
In
tent
-to-
Tre
at
Pro
toco
l Num
ber:
BT
-201
03 D
ecem
ber
2018
D
ocum
ent s
tatu
s: F
inal
SA
P V
ersi
on 2
.0 A
men
dmen
t 1.0
N
ovot
ech
- S
tric
tly C
onfid
entia
l
Pag
e 40
of 4
4
No
. T
itle
A
na
lys
is
Po
pu
lati
on
16.2
.6.1
.2
MA
D: I
ndiv
idua
l pG
SN
Pla
sma
Con
cent
ratio
ns (
unit)
In
tent
-to-
Tre
at
16.2
.6.2
.1
SD
: Ind
ivid
ual E
stim
ated
Pla
sma
rhu-
pGS
N C
once
ntra
tions
(un
it)
Inte
nt-t
o-T
reat
16
.2.6
.2.2
M
AD
: Ind
ivid
ual E
stim
ated
Pla
sma
rhu-
pGS
N P
lasm
a C
once
ntra
tions
(un
it)
Inte
nt-t
o-T
reat
16
.2.6
.3.1
S
D: I
ndiv
idua
l pG
SN
Pla
sma
PK
Par
amet
ers
Inte
nt-t
o-T
reat
16
.2.6
.3.2
M
AD
: Ind
ivid
ual p
GS
N P
lasm
a P
K P
aram
eter
s by
Day
In
tent
-to-
Tre
at
16.2
.6.4
.1
SD
: Ind
ivid
ual E
stim
ated
Pla
sma
rhu-
pGS
N P
lasm
a P
K P
aram
eter
s In
tent
-to-
Tre
at
16.2
.6.4
.2
MA
D: I
ndiv
idua
l Est
imat
ed P
lasm
a rh
u-pG
SN
Pla
sma
PK
Par
amet
ers
by D
ay
Inte
nt-t
o-T
reat
16
.2.6
.5.1
S
D: A
nti-r
hu-p
GS
N A
ntib
odie
s In
tent
-to-
Tre
at
16.2
.6.5
.2
MA
D: A
nti-r
hu-p
GS
N A
ntib
odie
s In
tent
-to-
Tre
at
16.2
.6.6
.1
SD
: Bio
mar
kers
In
tent
-to-
Tre
at
16.2
.6.6
.2
MA
D: B
iom
arke
rs
Inte
nt-t
o-T
reat
16
.2.6
.7.1
S
D: S
putu
m a
nd B
lood
Cul
ture
In
tent
-to-
Tre
at
16.2
.6.7
.2
MA
D: S
putu
m a
nd B
lood
Cul
ture
In
tent
-to-
Tre
at
16.2
.7.1
.1
SD
: Adv
erse
Eve
nts
Inte
nt-t
o-T
reat
16
.2.7
.1.2
M
AD
: Adv
erse
Eve
nts
Inte
nt-t
o-T
reat
16
.2.7
.2.1
S
D: S
erio
us A
dver
se E
vent
s In
tent
-to-
Tre
at
16.2
.7.2
.2
MA
D: S
erio
us A
dver
se E
vent
s In
tent
-to-
Tre
at
16.2
.7.3
.1
SD
: Adv
erse
Eve
nts
Lead
ing
to S
tudy
Med
icat
ion
Dis
cont
inua
tion
Inte
nt-t
o-T
reat
16
.2.7
.3.2
M
AD
: Adv
erse
Eve
nts
Lead
ing
to S
tudy
Med
icat
ion
Dis
cont
inua
tion
Inte
nt-t
o-T
reat
16
.2.7
.4.1
S
D: O
vera
ll S
urvi
val
Inte
nt-t
o-T
reat
16
.2.7
.4.2
M
AD
: Ove
rall
Sur
viva
l In
tent
-to-
Tre
at
16.2
.8.1
.1.1
S
D: C
BC
In
tent
-to-
Tre
at
16.2
.8.1
.1.2
M
AD
: CB
C
Inte
nt-t
o-T
reat
16
.2.8
.1.2
.1
SD
: Abn
orm
al C
BC
In
tent
-to-
Tre
at
16.2
.8.1
.2.2
M
AD
: Abn
orm
al C
BC
In
tent
-to-
Tre
at
16.2
.8.2
.1.1
S
D: C
oagu
latio
n In
tent
-to-
Tre
at
16.2
.8.2
.1.2
M
AD
: Coa
gula
tion
Inte
nt-t
o-T
reat
16
.2.8
.2.2
.1
SD
: Abn
orm
al C
oagu
latio
n In
tent
-to-
Tre
at
16.2
.8.2
.2.2
M
AD
: Abn
orm
al C
oagu
latio
n In
tent
-to-
Tre
at
16.2
.8.3
.1.1
S
D: C
ompr
ehen
sive
Met
abol
ic P
rofil
e In
tent
-to-
Tre
at
16.2
.8.3
.1.2
M
AD
: Com
preh
ensi
ve M
etab
olic
Pro
file
Inte
nt-t
o-T
reat
Pro
toco
l Num
ber:
BT
-201
03 D
ecem
ber
2018
D
ocum
ent s
tatu
s: F
inal
SA
P V
ersi
on 2
.0 A
men
dmen
t 1.0
N
ovot
ech
- S
tric
tly C
onfid
entia
l
Pag
e 41
of 4
4
No
. T
itle
A
na
lys
is
Po
pu
lati
on
16.2
.8.3
.2.1
S
D: A
bnor
mal
Com
preh
ensi
ve M
etab
olic
Pro
file
Inte
nt-t
o-T
reat
16
.2.8
.3.2
.2
MA
D: A
bnor
mal
Com
preh
ensi
ve M
etab
olic
Pro
file
Inte
nt-t
o-T
reat
16
.2.9
.1
SD
: Vita
l Sig
ns
Inte
nt-t
o-T
reat
16
.2.9
.2
MA
D: V
ital S
igns
In
tent
-to-
Tre
at
16.2
.10.
1 S
D: E
KG
In
tent
-to-
Tre
at
16.2
.10.
2 M
AD
: EK
G
Inte
nt-t
o-T
reat
16
.2.1
1.1
SD
: Phy
sica
l Exa
min
atio
n In
tent
-to-
Tre
at
16.2
.11.
2 M
AD
: Phy
sica
l Exa
min
atio
n In
tent
-to-
Tre
at
16.2
.12.
1.1
SD
: Out
com
e P
redi
ctio
n M
odel
s C
UR
B-6
5 In
tent
-to-
Tre
at
16.2
.12.
1.2
MA
D: O
utco
me
Pre
dict
ion
Mod
els
CU
RB
-65
Inte
nt-t
o-T
reat
16
.2.1
2.2.
1 S
D: O
utco
me
Pre
dict
ion
Mod
els
PS
I (P
ort S
core
) In
tent
-to-
Tre
at
16.2
.12.
2.2
MA
D: O
utco
me
Pre
dict
ion
Mod
els
PS
I (P
ort S
core
) In
tent
-to-
Tre
at
16.2
.12.
3.1
SD
: Out
com
e P
redi
ctio
n M
odel
s S
OF
A S
core
In
tent
-to-
Tre
at
16.2
.12.
3.2
MA
D: O
utco
me
Pre
dict
ion
Mod
els
SO
FA
Sco
re
Inte
nt-t
o-T
reat
16
.2.1
2.4.
1 S
D: O
utco
me
Pre
dict
ion
Mod
els
MM
SE
Sco
re
Inte
nt-t
o-T
reat
16
.2.1
2.4.
2 M
AD
: Out
com
e P
redi
ctio
n M
odel
s M
MS
E S
core
In
tent
-to-
Tre
at
16.2
.13.
1 S
D: C
onco
mita
nt M
edic
atio
ns
Inte
nt-t
o-T
reat
16
.2.1
3.2
MA
D: C
onco
mita
nt M
edic
atio
n In
tent
-to-
Tre
at
16.2
.14.
1 S
D: H
ospi
taliz
atio
n F
ollo
w-U
p In
tent
-to-
Tre
at
16.2
.14.
2 M
AD
: Hos
pita
lizat
ion
Fol
low
-Up
Inte
nt-t
o-T
reat
Pro
toco
l Num
ber:
BT
-201
03 D
ecem
ber
2018
D
ocum
ent s
tatu
s: F
inal
SA
P V
ersi
on 2
.0 A
men
dmen
t 1.0
N
ovot
ech
- S
tric
tly C
onfid
entia
l
Pag
e 42
of 4
4
19.
FIG
UR
ES
No
. T
itle
A
na
lys
is
Po
pu
lati
on
14
.2.1
.1
Indi
vidu
al p
GS
N P
lasm
a C
once
ntra
tions
(ng
/mL)
(Li
near
sca
le)
by D
ay
PK
14
.2.1
.2
Indi
vidu
al p
GS
N P
lasm
a C
once
ntra
tions
(ng
/mL)
(S
emi-l
ogar
ithm
ic)
by D
ay
PK
14
.2.2
.1
Indi
vidu
al E
stim
ated
Pla
sma
rhu-
pGS
N P
lasm
a C
once
ntra
tions
(ng
/mL)
bas
ed o
n th
e D
oubl
e D
elta
Ana
lysi
s (L
inea
r sc
ale)
by
Day
P
K
14.2
.2.2
In
divi
dual
Est
imat
ed P
lasm
a rh
u-pG
SN
Pla
sma
Con
cent
ratio
ns (
ng/m
L) b
ased
on
the
Dou
ble
Del
ta A
naly
sis
(Lin
ear
scal
e)
by D
ay
PK
14.2
.3.1
M
ean
(+/-
SD
) pG
SN
Pla
sma
Con
cent
ratio
ns (
ng/m
L) (
Line
ar s
cale
) by
Day
P
K
14.2
.3.2
M
ean
(+/-
SD
) pG
SN
Pla
sma
Con
cent
ratio
ns (
ng/m
L) b
ased
on
Cha
nges
from
Pre
-Inj
ectio
n (
Line
ar s
cale
) by
Day
(S
emi-
loga
rithm
ic)
by D
ay
PK
14.2
.4.1
M
ean
(+/-
SD
) E
stim
ated
Pla
sma
rhu-
pGS
N P
lasm
a C
once
ntra
tions
(ng
/mL)
bas
ed o
n C
hang
es fr
om P
re-I
njec
tion
(Li
near
sc
ale)
by
Day
P
K
14.2
.4.2
M
ean
(+/-
SD
) E
stim
ated
Pla
sma
rhu-
pGS
N P
lasm
a C
once
ntra
tions
(ng
/mL)
bas
ed o
n th
e D
oubl
e D
elta
Ana
lysi
s (L
inea
r sc
ale)
by
Day
P
K
14.3
.1.1
S
D: K
apla
n-M
eier
Plo
t of O
vera
ll S
urvi
val T
ime
Saf
ety
14.3
.1.2
M
AD
: Kap
lan-
Mei
er P
lot o
f Ove
rall
Sur
viva
l Tim
e S
afet
y 14
.3.2
.1
SD
: Kap
lan-
Mei
er P
lot o
f Len
gth
of S
tay
in H
ospi
tal (
hour
s)
Saf
ety
14.3
.2.2
M
AD
: Kap
lan-
Mei
er P
lot o
f Len
gth
of S
tay
in H
ospi
tal (
hour
s)
Saf
ety
14.3
.3.1
S
D: K
apla
n-M
eier
Plo
t of D
urat
ion
of IC
U S
tay
Saf
ety
14.3
.3.2
M
AD
: Kap
lan-
Mei
er P
lot o
f Dur
atio
n of
ICU
Sta
y S
afet
y 14
.3.4
.1
SD
: Kap
lan-
Mei
er P
lot o
f Dur
atio
n of
Intu
batio
n S
afet
y 14
.3.4
.2
MA
D: K
apla
n-M
eier
Plo
t of D
urat
ion
of In
tuba
tion
Saf
ety
Pro
toco
l Num
ber:
BT
-201
03 D
ecem
ber
2018
D
ocum
ent s
tatu
s: F
inal
SA
P V
ersi
on 2
.0 A
men
dmen
t 1.0
N
ovot
ech
- S
tric
tly C
onfid
entia
l
Pag
e 43
of 4
4
20.
AP
PE
ND
ICE
S
No
. T
itle
A
na
lys
is
Po
pu
lati
on
14
.3.3
.9.1
S
D: S
umm
ary
of O
vera
ll S
urvi
val
Saf
ety
14.3
.3.9
.2
MA
D: S
umm
ary
of O
vera
ll S
urvi
val
Saf
ety
14.3
.4.1
3.1
SD
: Sum
mar
y of
Hos
pita
lizat
ion
Saf
ety
14.3
.4.1
3.2
MA
D: S
umm
ary
of H
ospi
taliz
atio
n S
afet
y
Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0
Novotech - Strictly Confidential Page 44 of 44
21. REFERENCES
1) Clinical Study Protocol Amendment 1.0, 30 April 2018.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
1 o
f 82
BT
I-201
: Moc
k Ta
bles
: Tab
le o
f Con
tent
s Tables
Tabl
e 14
.1.1
.1 S
D: S
umm
ary
of S
ubje
ct E
nrolm
ent
and
Disp
osit
ion
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
6
Tabl
e 14
.1.1
.2 M
AD:
Sum
mary
of
Subj
ect
Enrol
ment
and
Dis
posi
tion
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 7
Ta
ble
14.1
.2.1
SD:
Summ
ary
of D
emog
raph
ics a
nd B
asel
ine
Char
acter
isti
cs ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 8
Tabl
e 14
.1.2
.2 M
AD:
Summa
ry o
f De
mogr
aphi
cs
and
Base
line
Cha
racte
rist
ics
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 10
Tabl
e 14
.2.1
.1 D
ay 1
: S
umma
ry o
f Pl
asma
pGSN
Con
cent
rati
ons
(unit
) by
Tim
epoi
nt ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
11
Tabl
e 14
.2.1
.2 D
ay 2
: S
umma
ry o
f Pl
asma
pGSN
Con
cent
rati
ons
(unit
) by
Tim
epoi
nt ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
13
Tabl
e 14
.2.1
.3 D
ay 3
: S
umma
ry o
f Pl
asma
pGSN
Con
cent
rati
ons
(unit
) by
Tim
epoi
nt ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
15
Tabl
e 14
.2.1
.4 D
ay 1
: S
umma
ry o
f Es
tima
ted P
lasm
a rh
u-pG
SN C
oncen
trat
ions
(un
it)
by Ti
mepo
int
......
......
......
......
......
......
......
......
......
......
.....
16
Tabl
e 14
.2.1
.5 D
ay 2
: S
ummary
of
Esti
mate
d P
lasm
a rh
u-pG
SN C
oncen
trat
ions
(un
it)
by Ti
mepo
int
......
......
......
......
......
......
......
......
......
......
.....
18
Tabl
e 14
.2.1
.6 D
ay 3
: S
umma
ry o
f Es
tima
ted P
lasm
a rh
u-pG
SN C
oncen
trat
ions
(un
it)
by Ti
mepo
int
......
......
......
......
......
......
......
......
......
......
.....
20
Tabl
e 14
.2.2
.1 D
ay 1
: S
umma
ry o
f Pl
asma
pGSN
PK
Para
mete
rs ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 21
Tabl
e 14
.2.2
.2 D
ay 2
: S
umma
ry o
f Pl
asma
pGSN
PK
Para
mete
rs ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 22
Tabl
e 14
.2.2
.3 D
ay 3
: S
umma
ry o
f Pl
asma p
GSN
PK
Para
mete
rs ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 23
Tabl
e 14
.2.3
.1 D
ay 1
: S
umma
ry o
f Es
tima
ted P
lasm
a rh
u-pG
SN P
K Par
amet
ers
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 24
Tabl
e 14
.2.3
.2 D
ay 2
: S
umma
ry o
f Es
tima
ted P
lasm
a rh
u-pG
SN P
K Par
amet
ers
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 25
Tabl
e 14
.2.3
.3 D
ay 3
: S
umma
ry o
f Es
tima
ted P
lasm
a rh
u-pG
SN P
K Par
amet
ers
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 26
Tabl
e 14
.2.4
.1 S
D: S
umm
ary
of P
D Pa
rame
ters
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 2
7 Ta
ble
14.2
.4.2
MAD
: Sum
mary
of
PD P
aram
eters
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 28
Tabl
e 14
.2.5
.1 S
D: S
umm
ary
of P
D Pa
rame
ters
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 2
9 Ta
ble
14.2
.5.2
MAD
: Sum
mary
of
PD P
aram
eters
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 30
Tabl
e 14
.3.1
.1 S
D: S
umm
ary
of C
onco
mita
nt Me
dica
tion
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
31
Tabl
e 14
.3.1
.2 M
AD:
Sum
mary
of
Prio
r an
d Con
comi
tant
Med
icat
ion
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 3
2 Ta
ble
14.3
.3.1
.1 S
D: Ov
eral
l Su
mmar
y of
Trea
tmen
t-Em
erge
nt A
dvers
e Ev
ents
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
33
Tabl
e 14
.3.3
.1.2
MAD
: O
vera
ll S
umma
ry o
f Tre
atme
nt-E
merg
ent
Adver
se E
vent
s ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
34
Tabl
e 14
.3.3
.2.1
SD:
Su
mmar
y of
Tre
atme
nt-Em
erge
nt A
dver
se E
vents
(Su
mmar
y by
SOC
, PT)
.....
......
......
......
......
......
......
......
......
......
......
......
......
.... 3
5 Ta
ble
14.3
.3.2
.2 M
AD: S
umma
ry o
f Tr
eatm
ent-E
merg
ent
Adve
rse
Event
s (S
umma
ry b
y SO
C, PT
) ...
......
......
......
......
......
......
......
......
......
......
......
......
.... 3
6 Ta
ble
14.3
.3.3
.1 S
D: Su
mmar
y of
Tre
atme
nt-Em
erge
nt D
eath
s (S
ummar
y by
SOC
, PT
) ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 37
Ta
ble
14.3
.3.3
.2 M
AD: S
umma
ry o
f Tr
eatm
ent-E
merg
ent
Deat
hs (
Summa
ry b
y SO
C, P
T) ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
38
Tabl
e 14
.3.3
.4.1
SD:
Su
mmar
y of
Ser
ious
Trea
tmen
t-Em
erge
nt A
dvers
e Ev
ents
(Su
mmar
y by
SOC,
PT)
.....
......
......
......
......
......
......
......
......
......
... 3
9 Ta
ble
14.3
.3.4
.2 M
AD: S
umma
ry o
f Se
riou
s Tre
atme
nt-E
merg
ent
Adver
se E
vent
s (S
umma
ry by
SOC
, PT
) ...
......
......
......
......
......
......
......
......
......
... 4
0 Ta
ble
14.3
.3.5
.1 S
D: Su
mmar
y of
Tre
atme
nt-Em
erge
nt A
dver
se E
vents
(Su
mmar
y by
SOC
, PT
and
NCI-CT
CAE
Grad
e)
......
......
......
......
......
.... 4
1 Ta
ble
14.3
.3.5
.2 M
AD: S
umma
ry o
f Tr
eatm
ent-E
merg
ent
Adve
rse
Event
s (S
umma
ry b
y SO
C, PT
and
NCI
-CTC
AE G
rade)
.....
......
......
......
......
.. 42
Ta
ble
14.3
.1.6
.1 S
D: Su
mmar
y of
Tre
atme
nt-Em
erge
nt A
dver
se E
vents
(Su
mmar
y by
SOC
, PT
and
Rela
tion
ship
to S
tudy
Dru
g)...
.....
43
Tabl
e 14
.3.3
.6.2
MAD
: S
umma
ry o
f Tr
eatm
ent-E
merg
ent
Adve
rse
Event
s (S
umma
ry b
y SO
C, PT
and
Rel
atio
nshi
p to
Stud
y Dr
ug)
.....
44
Tabl
e 14
.3.3
.7.1
SD:
Su
mmar
y of
Tre
atme
nt-Em
erge
nt A
dver
se E
vents
(Su
mmar
y by
SOC
, PT
and
Rela
tion
ship
to Stu
dy P
roce
dure
)...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 45
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
2 o
f 82
Tabl
e 14
.3.3
.7.2
MAD
: S
umma
ry o
f Tr
eatm
ent-E
merg
ent
Adve
rse
Event
s (S
umma
ry b
y SO
C, PT
and
Rel
atio
nshi
p to
Study
Proc
edur
e) ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 46
Tabl
e 14
.3.3
.8.1
SD:
Su
mmar
y of
Tre
atme
nt-Em
erge
nt A
dver
se E
vents
Lea
ding
to
Trea
tment
Dis
cont
inua
tion
(Sum
mary
by
SOC,
PT
) ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
47
Tabl
e 14
.3.3
.8.2
MAD
: S
umma
ry o
f Tr
eatm
ent-E
merg
ent
Adve
rse
Event
s Le
adin
g to
Tre
atmen
t Di
scon
tinu
atio
n (Su
mmar
y by
SOC
, PT
) ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
48
Tabl
e 14
.3.3
.9.1
SD:
Su
mmar
y of
Ove
rall
Surv
ival
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 4
9 Ta
ble
14.3
.3.9
.2 M
AD: S
umma
ry o
f Ov
eral
l Sur
viva
l ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
50
Tabl
e 14
.3.4
.1.1
.1 S
D:
Summ
ary
of C
BC (
Summa
ry o
f Ac
tual
and
Chan
ge f
rom
Base
line
Valu
es)
by T
imep
oint
.....
......
......
......
......
......
......
.. 51
Ta
ble
14.3
.4.1
.1.2
MAD:
Sum
mary
of
CBC
(Summ
ary
of A
ctua
l an
d Cha
nge
from
Bas
elin
e Val
ues)
by
Time
poin
t ...
......
......
......
......
......
......
.. 52
Ta
ble
14.3
.4.1
.2.1
SD:
Summ
ary
of C
BC S
hifts
fro
m Ba
seli
ne (
Low,
Norm
al,
High
) ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 53
Ta
ble
14.3
.4.1
.2.2
MAD:
Sum
mary
of
CBC
Shift
s fr
om B
asel
ine
(Low,
Nor
mal,
Hig
h) ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
54
Tabl
e 14
.3.4
.2.1
.1 S
D:
Summ
ary
of C
oagu
latio
n (S
umma
ry o
f Ac
tual
and
Chan
ge f
rom
Basel
ine
Valu
es)
by T
imepo
int
.....
......
......
......
. 55
Tabl
e 14
.3.4
.2.1
.2 M
AD:
Sum
mary
of
Coag
ulati
on (
Summ
ary
of A
ctual
and
Cha
nge
from
Base
line
Val
ues)
by
Timep
oint
......
......
......
.... 5
6 Ta
ble
14.3
.4.2
.2.1
SD:
Summ
ary
of C
oagu
latio
n Sh
ifts
fro
m Ba
selin
e (L
ow,
Norm
al,
High)
.....
......
......
......
......
......
......
......
......
......
......
......
......
.... 5
7 Ta
ble
14.3
.4.2
.2.2
MAD:
Sum
mary
of
Coag
ulati
on S
hift
s fr
om B
aseli
ne (
Low,
Nor
mal,
High
) ...
......
......
......
......
......
......
......
......
......
......
......
......
.... 5
8 Ta
ble
14.3
.4.3
.1.1
SD:
Summ
ary
of C
ompr
ehens
ive
Meta
boli
c Pr
ofile
(Su
mmar
y of
Act
ual a
nd C
hang
e fr
om B
aseli
ne V
alue
s) b
y Ti
mepo
int
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 59
Tabl
e 14
.3.4
.3.1
.2 M
AD:
Sum
mary
of
Comp
rehen
sive
Met
abol
ic P
rofil
e (S
umma
ry o
f Ac
tual
and
Chan
ge f
rom
Basel
ine
Valu
es)
by
Time
poin
t ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 6
0 Ta
ble
14.3
.4.3
.2.1
SD:
Summ
ary
of C
ompr
ehens
ive
Meta
boli
c Pr
ofile
Shi
fts
from
Bas
eline
(Lo
w, N
orma
l, H
igh)
......
......
......
......
......
.... 6
1 Ta
ble
14.3
.4.3
.2.2
MAD:
Sum
mary
of
Comp
rehen
sive
Met
abol
ic P
rofil
e Sh
ifts
fro
m Ba
selin
e (L
ow,
Norm
al,
High)
.....
......
......
......
......
.. 62
Ta
ble
14.3
.4.4
.1 S
D: Su
mmar
y of
Vit
al S
igns
(Sum
mary
of
Actu
al an
d Ch
ange
fro
m Ba
selin
e Va
lues
) by
Tim
epoin
t ...
......
......
......
......
.. 63
Ta
ble
14.3
.4.4
.2 M
AD: S
umma
ry o
f Vi
tal
Signs
(Su
mmar
y of
Act
ual a
nd C
hang
e fr
om B
aseli
ne V
alue
s) b
y Ti
mepoi
nt...
......
......
......
......
64
Tabl
e 14
.3.4
.5.1
SD:
Su
mmar
y of
Vit
al S
igns
Inte
rpre
tati
on b
y Tim
epoi
nt ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
65
Tabl
e 14
.3.4
.5.2
MAD
: S
umma
ry o
f Vi
tal
Signs
Int
erpr
etat
ion
by Ti
mepo
int
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 66
Tabl
e 14
.3.4
.6.1
SD:
Su
mmar
y of
Mea
n EK
G (Su
mmar
y of
Act
ual
and C
hang
e fr
om B
asel
ine V
alue
s) b
y Ti
mepo
int
......
......
......
......
......
......
67
Tabl
e 14
.3.4
.6.2
MAD
: S
umma
ry o
f Me
an E
KG (S
umma
ry o
f Ac
tual
and
Chan
ge f
rom
Base
line
Valu
es)
by T
imep
oint
......
......
......
......
......
.... 6
8 Ta
ble
14.3
.4.7
.1 S
D: Su
mmar
y of
EKG
Int
erpre
tati
on (
Wors
t) b
y Tim
epoi
nt ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
69
Tabl
e 14
.3.4
.7.2
MAD
: S
umma
ry o
f EK
G In
terpr
etat
ion
(Wor
st)
by Ti
mepo
int
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 70
Tabl
e 14
.3.4
.8.1
SD:
Su
mmar
y of
CUR
B-65
Scor
e(Su
mmar
y of
Act
ual a
nd C
hang
e fr
om B
aseli
ne V
alue
s) b
y Ti
mepoi
nt...
......
......
......
......
71
Tabl
e 14
.3.4
.8.2
MAD
: S
umma
ry o
f CU
RB-6
5 Sco
re (
Summ
ary
of A
ctual
and
Cha
nge
from
Base
line
Val
ues)
by
Timep
oint
......
......
......
.... 7
2 Ta
ble
14.3
.4.9
.1 S
D: Su
mmar
y of
PSI
Sco
re (S
umma
ry o
f Ac
tual
and
Chan
ge f
rom
Base
line
Valu
es)
by T
imep
oint
......
......
......
......
......
.... 7
3 Ta
ble
14.3
.4.9
.2 M
AD: S
umma
ry o
f PS
I Sc
ore (
Summ
ary
of A
ctua
l and
Cha
nge
from
Bas
eline
Val
ues)
by
Time
point
.....
......
......
......
......
.. 74
Ta
ble
14.3
.4.1
0.1
SD: S
umma
ry o
f PS
I Risk
Cl
ass
by T
imep
oint
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
75
Tabl
e 14
.3.4
.10.
2 MA
D:
Summ
ary
of P
SI R
isk C
lass
by
Time
poin
t ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
76
Tabl
e 14
.3.4
.11.
1 SD
: S
umma
ry o
f SO
FA S
core
(Sum
mary
of
Actu
al an
d Ch
ange
fro
m Ba
selin
e Va
lues
) by
Tim
epoin
t ...
......
......
......
......
.. 77
Ta
ble
14.3
.4.1
1.2
MAD:
Summ
ary
of S
OFA
Score
(Su
mmar
y of
Act
ual a
nd C
hang
e fr
om B
aseli
ne V
alue
s) b
y Ti
mepoi
nt...
......
......
......
......
78
Tabl
e 14
.3.4
.12.
1 SD
: S
umma
ry o
f MM
SE S
core
(Sum
mary
of
Actu
al an
d Ch
ange
fro
m Ba
selin
e Va
lues
) by
Tim
epoin
t ...
......
......
......
......
.. 79
Ta
ble
14.3
.4.1
2.2
MAD:
Summ
ary
of M
MSE
Score
(Su
mmar
y of
Act
ual a
nd C
hang
e fr
om B
aseli
ne V
alue
s) b
y Ti
mepoi
nt...
......
......
......
......
80
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
3 o
f 82
Tabl
e 14
.3.4
.13.
1 SD
: S
umma
ry o
f Ho
spit
aliza
tion
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 8
1 Ta
ble
14.3
.4.1
3.2
MAD:
Summ
ary
of H
ospi
taliz
atio
n ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
82
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
4 o
f 82
GEN
ERAL
CO
MM
ENTS
W
here
a c
ount
is 0
, the
per
cent
age
will
not
be
show
n (e
.g. 0
(0.0
%) w
ill b
e di
spla
yed
as 0
)
Unl
ess o
ther
wise
stat
es, p
aram
eter
s will
be
liste
d in
alp
habe
tical
ord
er
Pe
rcen
tage
s and
thei
r 95%
CI,
whe
re a
ppro
pria
te, w
ill b
e pr
esen
ted
to o
ne d
ecim
al p
lace
The
min
imum
and
max
imum
val
ues w
ill b
e pr
esen
ted
to th
e sa
me
num
ber o
f dec
imal
pla
ces a
s rec
orde
d in
the
elec
tron
ic C
ase
Repo
rt F
orm
(eCR
F)
M
ean,
med
ian,
and
SD
will
be
pres
ente
d to
one
mor
e de
cim
al p
lace
than
the
raw
dat
a
Perc
enta
ges w
ill b
e ro
unde
d to
one
dec
imal
pla
ce, w
ith th
e de
nom
inat
or b
eing
the
num
ber o
f sub
ject
s in
the
rele
vant
pop
ulat
ion
with
non
-miss
ing
data
, unl
ess
othe
rwise
spec
ified
Chan
ge fr
om B
asel
ine:
Ch
ange
from
Bas
elin
e w
ill b
e ca
lcul
ated
as:
U
nsch
edul
ed v
isits
will
be
excl
uded
from
sum
mar
y ta
bles
Nam
es a
nd o
rder
of T
reat
men
t Gro
ups
SD:
rh
u-pG
SN 6
mg/
kg;
Pl
aceb
o;
O
vera
ll.
MAD
: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Plac
ebo;
Ove
rall.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
5 o
f 82
N
ames
of v
isits
SD
:
Scre
enin
g
Day
1
Day
2
Day
3/4
Da
y 7
Da
y 14
Day
28 /
Early
Ter
min
atio
n (C
ombi
ned
visit
for s
afet
y an
d PD
)
MAD
: Sc
reen
ing
Da
y 1
Da
y 2
Da
y 3
Da
y 4
Da
y 7
Da
y 14
Day
28 /
Early
Ter
min
atio
n (C
ombi
ned
visit
for s
afet
y an
d PD
)
Colu
mn
wid
ths a
nd te
xt-w
rapp
ing
may
be
alte
red
in fi
nal o
utpu
t in
orde
r to
best
pre
sent
the
data
Foot
note
s may
be
adde
d/am
ende
d if
requ
ired
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
6 o
f 82
Table 14.1.1.1 SD: Summary of Subject Enrolment and Disposition
Protocol: BTI-201
Intent-to-Treat Population
rhu-pGSN
6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Number of Subjects Screened
xx
xx
xx
Number of Screening Failures1
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects Randomized
xx
xx
xx
Number of Subjects who Completed the Study
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects Discontinued
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Primary Reason for Discontinuation of Study
Due to Adverse Event
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Subject withdrew consent
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Investigator Decision
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Non-Compliance with the study procedures/protocol
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Any clinically significant change in subject’s medical condition
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Sponsor ended study
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Lost to follow-up
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Other
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects included in the ITT Population
x (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects included in the Safety Population
x (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects included in the PK Population
x (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects included in the PP Population
x (xx.x%)
xx (xx.x%)
xx (xx.x%)
1Percentages are based on number of subjects screened.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
7 o
f 82
Table 14.1.1.2 MAD: Summary of Subject Enrolment and Disposition
Protocol: BTI-201
Intent-to-Treat Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.1.
1.1
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
8 o
f 82
Table 14.1.2.1 SD: Summary of Demographics and Baseline Characteristics
Protocol: BTI-201
Intent-to-Treat Population
rhu-pGSN
6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Age (years) at Screening
n
xx
xx
xx
Mean
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
SD
x.x
x.x
xx.x
Minimum
xx
xx
xx
Maximum
xx
xx
xx
Sex n(%)
Female
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Male
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Race n(%)
Asian
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Pacific Islander
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Black or African
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Pacific Islander
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Aborigine/Torres Strait Islander
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
White
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Other
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Childbearing Potential n(%)*
Yes
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
No
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
*Percentages are based on the number of female participants.
SD: Standard Deviation
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
9 o
f 82
Table 14.1.2.1 SD: Summary of Demographics and Baseline Characteristics
Protocol: BTI-201
Intent-to-Treat Population
rhu-pGSN
6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Height (cm)
n
xx
xx
xx
Mean
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
SD
x.x
x.x
xx.x
Minimum
xx
xx
xx
Maximum
xx
xx
xx
Weight (kg)
n
xx
xx
xx
Mean
xx.x
xx.x
xx.x
Median
xx.x
xx.x
xx.x
SD
x.x
x.x
xx.x
Minimum
xx
xx
xx
Maximum
xx
xx
xx
*Percentages are based on the number of female participants.
SD: Standard Deviation
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
10
of 8
2 Table 14.1.2.2 MAD: Summary of Demographics and Baseline Characteristics
Protocol: BTI-201
Intent-to-Treat Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name (version x.x), Output: filepath_name Created: DDMMMYYYY
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.1.
2.1
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
11
of 8
2 Table 14.2.1.1 Day 1: Summary of Plasma pGSN Concentrations (unit) by Timepoint
Protocol: BTI-201
PK Population
Time Point
SD/MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
Placebo
(N=xx)
Actual
Value
Ratio
from Pre-
Injection
Ratio from
Pre-
Injection/
Placebo
Ratio from
Pre-
Injection
Actual
Value
Ratio
from Pre-
Injection
Ratio from
Pre-
Injection/
Placebo
Ratio from
Pre-
Injection
Actual
Value
Ratio
from Pre-
Injection
Pre-Injection
n
x
x
x
Mean
x.x
x.x
x.x
Median
x.x
x.x
x.x
SD
x.x
x.x
x.x
Minimum
x
x
x
Maximum
x
x
x
CV%
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
5 to 10 mins post
n
x
x
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
ln SD
x.x
x.x
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
….
SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%; BLQ: Below Limit of Quantification
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
12
of 8
2 Table 14.2.1.1 Day 1: Summary of Plasma pGSN Concentrations (unit) by Timepoint (continued)
Protocol: BTI-201
PK Population
Time Point
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Placebo
(N=xx)
Actual Value
Ratio from
Pre-Injection
Ratio from Pre-
Injection/
Placebo Ratio
from Pre-
Injection
Actual Value
Ratio
from Pre-Injection
Pre-Injection
n
x
x
Mean
x.x
x.x
Median
x.x
x.x
SD
x.x
x.x
Minimum
x
x
Maximum
x
x
CV%
x.x
x.x
GeoMean
x.x
x.x
GeoCV%
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
5 to 10 mins post
n
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
Maximum
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
ln SD
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
….
SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%; BLQ: Below Limit of Quantification
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
13
of 8
2 Table 14.2.1.2 Day 2: Summary of Plasma pGSN Concentrations (unit) by Timepoint
Protocol: BTI-201
PK Population
Time Point
MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
Placebo
(N=xx)
Actual
Value
Ratio
from Pre-
Injection
Ratio from
Pre-
Injection/
Placebo
Ratio from
Pre-
Injection
Actual
Value
Ratio
from Pre-
Injection
Ratio from
Pre-
Injection/
Placebo
Ratio from
Pre-
Injection
Actual
Value
Ratio
from Pre-
Injection
Pre-Injection
n
x
x
x
Mean
x.x
x.x
x.x
Median
x.x
x.x
x.x
SD
x.x
x.x
x.x
Minimum
x
x
x
Maximum
x
x
x
CV%
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
5 to 10 mins post
n
x
x
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
ln SD
x.x
x.x
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
….
SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%; BLQ: Below Limit of Quantification
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
14
of 8
2 Table 14.2.1.2 Day 2: Summary of Plasma pGSN Concentrations (unit) by Timepoint (continued)
Protocol: BTI-201
PK Population
Time Point
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Placebo
(N=xx)
Actual Value
Ratio from
Pre-Injection
Ratio from Pre-
Injection/
Placebo Ratio
from Pre-
Injection
Actual Value
Ratio
from Pre-Injection
Pre-Injection
n
x
x
Mean
x.x
x.x
Median
x.x
x.x
SD
x.x
x.x
Minimum
x
x
Maximum
x
x
CV%
x.x
x.x
GeoMean
x.x
x.x
GeoCV%
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
5 to 10 mins post
n
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
Maximum
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
ln SD
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
x (xx.x%)
….
SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%; BLQ: Below Limit of Quantification
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
15
of 8
2 Table 14.2.1.3 Day 3: Summary of Plasma pGSN Concentrations (unit) by Timepoint
Protocol: BTI-201
PK Population
Prog
ram
min
g N
ote:
Rep
eat T
able
14.
2.1.
2 fo
r Day
3.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
16
of 8
2 Table 14.2.1.4 Day 1: Summary of Estimated Plasma rhu-pGSN Concentrations (unit) by Timepoint
Protocol: BTI-201
PK Population
Time Point
SD/MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
Placebo
(N=xx)
Actual
Value
Change
from Pre-
Injection
(Change from
Pre-
Injection)-
(Mean Placebo
Change from
Pre-
Injection)
Actual
Value
Change
from Pre-
Injection
(Change from
Pre-
Injection)-
(Mean Placebo
Change from
Pre-
Injection)
Actual
Value
Change
from Pre-
Injection
Pre-Injection
n
x
x
x
Mean
x.x
x.x
x.x
Median
x.x
x.x
x.x
SD
x.x
x.x
x.x
Minimum
x
x
x
Maximum
x
x
x
CV%
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
5 to 10 mins post
n
x
x
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
….
SD: Standard Deviation; BLQ: Below Limit of Quantification
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
17
of 8
2 Table 14.2.1.4 Day 1: Summary of Estimated Plasma rhu-pGSN Concentrations (unit) by Timepoint (continued)
Protocol: BTI-201
PK Population
Time Point
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Placebo
(N=xx)
Actual Value
Change from
Pre-Injection
(Change from Pre-
Injection)-
(Mean Placebo
Change from Pre-
Injection)
Actual Value
Change
from Pre-Injection
Pre-Injection
n
x
x
Mean
x.x
x.x
Median
x.x
x.x
SD
x.x
x.x
Minimum
x
x
Maximum
x
x
CV%
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
5 to 10 mins post
n
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
Maximum
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
….
SD: Standard Deviation; BLQ: Below Limit of Quantification
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
18
of 8
2 Table 14.2.1.5 Day 2: Summary of Estimated Plasma rhu-pGSN Concentrations (unit) by Timepoint
Protocol: BTI-201
PK Population
Time Point
MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
Placebo
(N=xx)
Actual
Value
Change
from Pre-
Injection
(Change from
Pre-
Injection)-
(Mean Placebo
Change from
Pre-
Injection)
Actual
Value
Change
from Pre-
Injection
(Change from
Pre-
Injection)-
(Mean Placebo
Change from
Pre-
Injection)
Actual
Value
Change
from Pre-
Injection
Pre-Injection
n
x
x
x
Mean
x.x
x.x
x.x
Median
x.x
x.x
x.x
SD
x.x
x.x
x.x
Minimum
x
x
x
Maximum
x
x
x
CV%
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
5 to 10 mins post
n
x
x
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
x (xx.x%)
….
SD: Standard Deviation; BLQ: Below Limit of Quantification
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
19
of 8
2 Table 14.2.1.5 Day 2: Summary of Estimated Plasma rhu-pGSN Concentrations (unit) by Timepoint (continued)
Protocol: BTI-201
PK Population
Time Point
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Placebo
(N=xx)
Actual Value
Change from
Pre-Injection
(Change from
Pre-Injection)-
(Mean Placebo
Change from Pre-
Injection)
Actual Value
Change
from Pre-Injection
Pre-Injection
n
x
x
Mean
x.x
x.x
Median
x.x
x.x
SD
x.x
x.x
Minimum
x
x
Maximum
x
x
CV%
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
5 to 10 mins post
n
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
Maximum
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
BLQ
x (xx.x%)
x (xx.x%)
….
SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%; BLQ: Below Limit of Quantification
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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tly C
onfid
entia
l
Page
20
of 8
2 Table 14.2.1.6 Day 3: Summary of Estimated Plasma rhu-pGSN Concentrations (unit) by Timepoint
Protocol: BTI-201
PK Population
Prog
ram
min
g N
ote:
Rep
eat T
able
14.
2.1.
5 fo
r Day
3.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
21
of 8
2 Table 14.2.2.1 Day 1: Summary of Plasma pGSN PK Parameters
Protocol: BTI-201
PK Population
Parameter (unit)
SD/MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Placebo
(N=xx)
AUC0-t (unit)
n
x
x
x
x
Mean
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
Median
x
x
x
x
Maximum
x
x
x
x
CV%
x.x
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
Cmax (unit)
n
x
x
x
x
Mean
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
Median
x
x
x
x
Maximum
x
x
x
x
CV%
x.x
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll PK
par
amet
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
22
of 8
2 Table 14.2.2.2 Day 2: Summary of Plasma pGSN PK Parameters
Protocol: BTI-201
PK Population
Parameter (unit)
MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Placebo
(N=xx)
AUC0-t (unit)
n
x
x
x
x
Mean
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
Median
x
x
x
x
Maximum
x
x
x
x
CV%
x.x
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
Cmax (unit)
n
x
x
x
x
Mean
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
Median
x
x
x
x
Maximum
x
x
x
x
CV%
x.x
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll PK
par
amet
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
23
of 8
2 Table 14.2.2.3 Day 3: Summary of Plasma pGSN PK Parameters
Protocol: BTI-201
PK Population
Parameter (unit)
MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Placebo
(N=xx)
AUC0-t (unit)
n
x
x
x
x
Mean
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
Median
x
x
x
x
Maximum
x
x
x
x
CV%
x.x
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
Cmax (unit)
n
x
x
x
x
Mean
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
Median
x
x
x
x
Maximum
x
x
x
x
CV%
x.x
x.x
x.x
x.x
GeoMean
x.x
x.x
x.x
x.x
GeoCV%
x.x
x.x
x.x
x.x
SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll PK
par
amet
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
24
of 8
2 Table 14.2.3.1 Day 1: Summary of Estimated Plasma rhu-pGSN PK Parameters
Protocol: BTI-201
PK Population
Parameter (unit)
SD/MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Change from
Pre-Injection
Double Delta
Analysis
Change from
Pre-Injection
Double Delta
Analysis
Change from
Pre-Injection
Double Delta
Analysis
AUC0-t (unit)
n
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
Cmax (unit)
n
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
SD: Standard Deviation;
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Incl
ude
the
follo
win
g: P
K pa
ram
eter
s (in
clud
ing
dose
nor
mal
ized
para
met
ers)
:
A
UC
0-t
A
UC
0-8h
C m
ax
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
25
of 8
2 Table 14.2.3.2 Day 2: Summary of Estimated Plasma rhu-pGSN PK Parameters
Protocol: BTI-201
PK Population
Parameter (unit)
MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Change from
Pre-Injection
Double Delta
Analysis
Change from
Pre-Injection
Double Delta
Analysis
Change from
Pre-Injection
Double Delta
Analysis
AUC0-t (unit)
n
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
Cmax (unit)
n
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
SD: Standard Deviation;
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Incl
ude
the
follo
win
g: P
K pa
ram
eter
s (in
clud
ing
dose
nor
mal
ized
para
met
ers)
:
A
UC
0-t
A
UC
0-8h
C m
ax
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
26
of 8
2 Table 14.2.3.3 Day 3: Summary of Estimated Plasma rhu-pGSN PK Parameters
Protocol: BTI-201
PK Population
Parameter (unit)
MAD
rhu-pGSN
6 mg/kg
(N=xx)
MAD
rhu-pGSN
12 mg/kg
(N=xx)
MAD
rhu-pGSN
24 mg/kg
(N=xx)
Change from
Pre-Injection
Double Delta
Analysis
Change from
Pre-Injection
Double Delta
Analysis
Change from
Pre-Injection
Double Delta
Analysis
AUC0-t (unit)
n
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
Cmax (unit)
n
x
x
x
x
x
x
Mean
x.x
x.x
x.x
x.x
x.x
x.x
SD
x.x
x.x
x.x
x.x
x.x
x.x
Minimum
x.x
x.x
x.x
x.x
x.x
x.x
Median
x
x
x
x
x
x
Maximum
x
x
x
x
x
x
CV%
x.x
x.x
x.x
x.x
x.x
x.x
SD: Standard Deviation;
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Incl
ude
the
follo
win
g: P
K pa
ram
eter
s (in
clud
ing
dose
nor
mal
ized
para
met
ers)
:
A
UC
0-t
A
UC
0-8h
C m
ax
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
27
of 8
2 Table 14.2.4.1 SD: Summary of PD Parameters
Protocol: BTI-201
Intent-to-Treat Population
Parameter
Visit
rhu-pGSN 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value
Ratio from
Baseline1
Actual
Value
Ratio from
Baseline1
Actual Value
Ratio from
Baseline1
Procalcitonin (unit)
Baseline1
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
GeoMean
x.xxx
x.xxx
x.xxx
Day 2
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
ln SD
x.xxx
x.xxx
x.xxx
GeoMean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
ln SD
x.xxx
x.xxx
x.xxx
GeoMean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
etc.
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll PD
par
amet
ers
and
all s
ched
uled
pos
t bas
elin
e tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
28
of 8
2 Table 14.2.4.2 MAD: Summary of PD Parameters
Protocol: BTI-201
Intent-to-Treat Population
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.2.
4.1
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
29
of 8
2 Table 14.2.5.1 SD: Summary of PD Parameters
Protocol: BTI-201
Per Protocol Population
Parameter
Visit
rhu-pGSN 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value
Ratio from
Baseline1
Actual
Value
Ratio from
Baseline1
Actual Value
Ratio from
Baseline1
Procalcitonin (unit)
Baseline1
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
GeoMean
x.xxx
x.xxx
x.xxx
Day 2
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
ln SD
x.xxx
x.xxx
x.xxx
GeoMean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
ln SD
x.xxx
x.xxx
x.xxx
GeoMean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
etc.
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Rep
eat f
or a
ll PD
par
amet
ers
and
all s
ched
uled
pos
t bas
elin
e tim
epoi
nts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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entia
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Page
30
of 8
2 Table 14.2.5.2 MAD: Summary of PD Parameters
Protocol: BTI-201
Per Protocol Population
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.2.
5.1
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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31
of 8
2 Table 14.3.1.1 SD: Summary of Concomitant Medication
Protocol: BTI-201
Safety Population
Anatomic Therapeutic Classification (ATC3)
Preferred Term (PT)
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Subjects with at least one Concomitant Medication
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
ATC3/1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
ATC3/2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
ATC3/3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Note: If a subject has multiple occurrences of a medication, the subject is presented only once in the subject count (N).
Occurrences are counted each time in the mentions/Occurrence (M) column.
WHO-DD, XXXX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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Page
32
of 8
2 Table 14.3.1.2 MAD: Summary of Prior and Concomitant Medication
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
1.1
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
33
of 8
2 Table 14.3.3.1.1 SD: Overall Summary of Treatment-Emergent Adverse Events
Protocol: BTI-201
Safety Population
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Number of subjects reporting at least:
One TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
One NCI-CTEAE Grade 3 TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
One Serious TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
One Drug Related TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
TEAE Leading to Death
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
One Procedure Related TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
One TEAE leading to study treatment discontinuation
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Number of subjects reporting TEAEs by NCI-CTEAE Grade
Grade 1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 5
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Number of subjects reporting TEAEs by relationship to study medication
Definitely not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Possibly Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely Related
Number of subjects reporting TEAEs by relationship to study procedure
Definitely not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Possibly Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely Related
Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following
the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once
in the Patient count (n) column for a given System Organ Class and Preferred Term. Occurrences are counted each time in the
mentions/occurrence (M) column. Related TEAE = A Possibly , Probably related TEAE or Definitely Related.MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
34
of 8
2 Table 14.3.3.1.2 MAD: Overall Summary of Treatment-Emergent Adverse Events
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.1.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
35
of 8
2 Table 14.3.3.2.1 SD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT)
Protocol: BTI-201
Safety Population
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Subjects with at least one TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT5
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following
the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once
in the Patient count (n) column for a given System Organ Class and Preferred Term.
Occurrences are counted each time in the mentions/Occurrence (M) column.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
36
of 8
2 Table 14.3.3.2.2 MAD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.2.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
37
of 8
2 Table 14.3.3.3.1 SD: Summary of Treatment-Emergent Deaths (Summary by SOC, PT)
Protocol: BTI-201
Safety Population
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Subjects with at least one TEAE leading to Death
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT5
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following
the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once
in the Patient count (n) column for a given System Organ Class and Preferred Term.
Occurrences are counted each time in the mentions/Occurrence (M) column.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
38
of 8
2 Table 14.3.3.3.2 MAD: Summary of Treatment-Emergent Deaths (Summary by SOC, PT)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.3.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
39
of 8
2 Table 14.3.3.4.1 SD: Summary of Serious Treatment-Emergent Adverse Events (Summary by SOC, PT)
Protocol: BTI-201
Safety Population
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Subjects with at least one Serious TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT5
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following
the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once
in the Patient count (n) column for a given System Organ Class and Preferred Term.
Occurrences are counted each time in the mentions/Occurrence (M) column.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
40
of 8
2 Table 14.3.3.4.2 MAD: Summary of Serious Treatment-Emergent Adverse Events (Summary by SOC, PT)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.4.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
41
of 8
2 Table 14.3.3.5.1 SD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and NCI-CTCAE Grade)
Protocol: BTI-201
Safety Population
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Subjects with at least one TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 5
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Grade 5
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following
the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once
in the Patient count (n) column for a given System Organ Class and Preferred Term.
Occurrences are counted each time in the mentions/Occurrence (M) column.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
42
of 8
2 Table 14.3.3.5.2 MAD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and NCI-CTCAE Grade)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.5.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
43
of 8
2 Table 14.3.1.6.1 SD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and Relationship to Study Drug)
Protocol: BTI-201
Safety Population
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Subjects with at least one TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Possibly Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Possibly Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following
the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once
in the Patient count (n) column for a given System Organ Class and Preferred Term.
Occurrences are counted each time in the mentions/Occurrence (M) column.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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44
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2 Table 14.3.3.6.2 MAD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and Relationship to Study Drug)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.6.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
45
of 8
2 Table 14.3.3.7.1 SD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and Relationship to Study Procedure)
Protocol: BTI-201
Safety Population
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Subjects with at least one TEAE
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Possibly Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably not Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Possibly Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Probably Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Definitely Related
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following
the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once
in the Patient count (n) column for a given System Organ Class and Preferred Term.
Occurrences are counted each time in the mentions/Occurrence (M) column.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
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onfid
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l
Page
46
of 8
2 Table 14.3.3.7.2 MAD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and Relationship to Study Procedure)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.7.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
47
of 8
2 Table 14.3.3.8.1 SD: Summary of Treatment-Emergent Adverse Events Leading to Treatment Discontinuation (Summary by SOC, PT)
Protocol: BTI-201
Safety Population
rhu-pGSN
6 mg/kg
(N=xx)
n (%) M
Placebo
(N=xx)
n (%) M
Overall
(N=xx)
n (%) M
Subjects with at least one TEAE Leading to Treatment Discontinuation
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
SOC2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT1
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT2
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT3
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT4
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT5
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
PT6
xx (xx.x%) xx
xx (xx.x%) xx
xx (xx.x%) xx
Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following
the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once
in the Patient count (n) column for a given System Organ Class and Preferred Term.
Occurrences are counted each time in the mentions/Occurrence (M) column.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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onfid
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l
Page
48
of 8
2 Table 14.3.3.8.2 MAD: Summary of Treatment-Emergent Adverse Events Leading to Treatment Discontinuation (Summary by SOC, PT)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.8.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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tly C
onfid
entia
l
Page
49
of 8
2 Table 14.3.3.9.1 SD: Summary of Overall Survival
Protocol: BTI-201
Safety Population
rhu-pGSN:
6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Deaths
Number of Subjects that Died
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects that did not Die
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Survival Time (days) (95% CI1)
25th Percentile
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Median
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
75th Percentile
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Note: CI = Confidence Interval; 1Brookmeyer and Crowley method (1982. Log-log transformation);
Overall Survival is defined as the difference (in days) between the
time of first study drug administration to the date of death + 1 (Include the day of the study drug administration.)
Subjects who did not die will be censored at the study exit visit.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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onfid
entia
l
Page
50
of 8
2 Table 14.3.3.9.2 MAD: Summary of Overall Survival
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
3.9.
1 In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
51
of 8
2 Table 14.3.4.1.1.1 SD: Summary of CBC (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Parameter
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value Change from
Baseline1
Actual Value Change from
Baseline1
Actual Value Change from
Baseline1
Hemoglobin (g/L)
Baseline1
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
Day 2
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
etc.
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l CBC
Par
amet
ers a
nd a
ll sc
hedu
led
time
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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onfid
entia
l
Page
52
of 8
2 Table 14.3.4.1.1.2 MAD: Summary of CBC (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.1.
1.1
Incl
ude
all C
BC P
aram
eter
s and
all
sche
dule
d tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
53
of 8
2 Table 14.3.4.1.2.1 SD: Summary of CBC Shifts from Baseline (Low, Normal, High)
Protocol: BTI-201
Safety Population
Parameter
Result
Classification
Baseline1
rhu-pGSN: 6 mg/kg
(N=xx)
Low
n (%)
Normal
n (%)
High
n (%)
Missing
n (%)
Total
n (%)
Hemoglobin (g/L)
Day 2
Low
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
High
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Missing
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Total
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Day 3 or 4
Low
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
High
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Missing
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Total
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
etc.
etc.
Note 1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Al
so In
clud
e: P
lace
bo,
O
vera
ll In
clud
e al
l CBC
Par
amet
ers a
nd a
ll sc
hedu
led
time
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
54
of 8
2 Table 14.3.4.1.2.2 MAD: Summary of CBC Shifts from Baseline (Low, Normal, High)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.1.
2.1
Incl
ude
all C
BC P
aram
eter
s and
all
sche
dule
d tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
55
of 8
2 Table 14.3.4.2.1.1 SD: Summary of Coagulation (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Parameter
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value Change from
Baseline1
Actual Value Change from
Baseline1
Actual Value Change from
Baseline1
PT/INR (unit)
Baseline1
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
Day 2
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
etc.
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l Coa
gula
tion
Para
met
ers a
nd a
ll sc
hedu
led
time
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
56
of 8
2 Table 14.3.4.2.1.2 MAD: Summary of Coagulation (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.2.
1.1
Incl
ude
all C
oagu
latio
n Pa
ram
eter
s and
all
sche
dule
d tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
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tly C
onfid
entia
l
Page
57
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2 Table 14.3.4.2.2.1 SD: Summary of Coagulation Shifts from Baseline (Low, Normal, High)
Protocol: BTI-201
Safety Population
Parameter
Result
Classification
Baseline1
rhu-pGSN: 6 mg/kg
(N=xx)
Low
n (%)
Normal
n (%)
High
n (%)
Missing
n (%)
Total
n (%)
PT/INR (unit)
Day 2
Low
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
High
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Missing
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Total
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Day 3 or 4
Low
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
High
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Missing
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Total
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
etc.
etc.
Note 1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Al
so In
clud
e: P
lace
bo,
O
vera
ll In
clud
e al
l Coa
gula
tion
Para
met
ers a
nd a
ll sc
hedu
led
time
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
58
of 8
2 Table 14.3.4.2.2.2 MAD: Summary of Coagulation Shifts from Baseline (Low, Normal, High)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.2.
2.1
Incl
ude
all C
oagu
latio
n Pa
ram
eter
s and
all
sche
dule
d tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
59
of 8
2 Table 14.3.4.3.1.1 SD: Summary of Comprehensive Metabolic Profile (Summary of Actual and Change from Baseline Values) by
Timepoint
Protocol: BTI-201
Safety Population
Parameter
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value Change from
Baseline1
Actual Value Change from
Baseline1
Actual Value Change from
Baseline1
Sodium (unit)
Baseline1
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
Day 2
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
etc.
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l Com
preh
ensiv
e M
etab
olic
Pro
file
Para
met
ers a
nd a
ll sc
hedu
led
time
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
60
of 8
2 Table 14.3.4.3.1.2 MAD: Summary of Comprehensive Metabolic Profile (Summary of Actual and Change from Baseline Values) by
Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.3.
1.1
Incl
ude
all C
ompr
ehen
sive
Met
abol
ic P
rofil
e Pa
ram
eter
s and
all
sche
dule
d tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
61
of 8
2 Table 14.3.4.3.2.1 SD: Summary of Comprehensive Metabolic Profile Shifts from Baseline (Low, Normal, High)
Protocol: BTI-201
Safety Population
Parameter
Result
Classification
Baseline1
rhu-pGSN: 6 mg/kg
(N=xx)
Low
n (%)
Normal
n (%)
High
n (%)
Missing
n (%)
Total
n (%)
Sodium (unit)
Day 2
Low
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
High
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Missing
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Total
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Day 3 or 4
Low
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
High
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Missing
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Total
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
etc.
etc.
Note 1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Al
so In
clud
e: P
lace
bo,
O
vera
ll In
clud
e al
l Com
preh
ensiv
e M
etab
olic
Pro
file
Para
met
ers a
nd a
ll sc
hedu
led
time
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
62
of 8
2 Table 14.3.4.3.2.2 MAD: Summary of Comprehensive Metabolic Profile Shifts from Baseline (Low, Normal, High)
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.3.
2.1
Incl
ude
all C
ompr
ehen
sive
Met
abol
ic P
rofil
e Pa
ram
eter
s and
all
sche
dule
d tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
63
of 8
2 Table 14.3.4.4.1 SD: Summary of Vital Signs (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Parameter
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value
Change from
Baseline1
Actual
Value
Change from
Baseline1
Actual Value Change from
Baseline1
Systolic blood
pressure (mmHg)
Baseline1
n
x
x
Mean
x.xxx
x.xxx
Median
x.xxx
x.xxx
SD
x.xxx
x.xxx
Minimum
x.xx
x.xx
Maximum
x.xx
x.xx
Day 1: End of
Infusion
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Day 1: 30 mins
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
etc.
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l Vita
l Sig
ns P
aram
eter
s and
all
time
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
64
of 8
2 Table 14.3.4.4.2 MAD: Summary of Vital Signs (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.4.
1 In
clud
e al
l Vita
l Sig
n Pa
ram
eter
s and
all
sche
dule
d tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
65
of 8
2 Table 14.3.4.5.1 SD: Summary of Vital Signs Interpretation by Timepoint
Protocol: BTI-201
Safety Population
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Baseline1
n
xx
xx
xx
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal NCS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal CS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Day 1: 30 mins
n
xx
xx
xx
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal NCS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal CS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Day 2
n
xx
xx
xx
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal NCS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal CS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
etc.
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
NCS = Not Clinically Significant; CS = Clinically Significant.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
66
of 8
2 Table 14.3.4.5.2 MAD: Summary of Vital Signs Interpretation by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.5.
1 In
clud
e al
l sch
edul
ed ti
me
poin
ts.
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
67
of 8
2 Table 14.3.4.6.1 SD: Summary of Mean EKG (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Parameter
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value
Change from
Baseline1
Actual
Value
Change from
Baseline1
Actual Value Change from
Baseline1
Heart Rate (unit)
Baseline1
n
x
x
Mean
x.xxx
x.xxx
Median
x.xxx
x.xxx
SD
x.xxx
x.xxx
Minimum
x.xx
x.xx
Maximum
x.xx
x.xx
Day 28 / Early
Termination
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
PR Interval (unit) B
aseline1
n
x
x
x
Mean
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
etc.
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l EKG
Par
amet
ers a
nd a
ll tim
e po
ints
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
68
of 8
2 Table 14.3.4.6.2 MAD: Summary of Mean EKG (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.6.
1 In
clud
e al
l EKG
Par
amet
ers a
nd a
ll sc
hedu
led
time
poin
ts.
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
69
of 8
2 Table 14.3.4.7.1 SD: Summary of EKG Interpretation (Worst) by Timepoint
Protocol: BTI-201
Safety Population
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Baseline1
n
xx
xx
xx
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal NCS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal CS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Day 28 / Early
Termination
n
xx
xx
xx
Normal
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal NCS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Abnormal CS
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
NCS = Not Clinically Significant; CS = Clinically Significant.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
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2 Table 14.3.4.7.2 MAD: Summary of EKG Interpretation (Worst) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Pr
ogra
mm
ing
Not
e:
Repe
at T
able
14.
3.4.
7.1
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
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71
of 8
2 Table 14.3.4.8.1 SD: Summary of CURB-65 Score(Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value
Change from
Baseline1
Actual
Value
Change from
Baseline1
Actual Value
Change from
Baseline1
Baseline1
n
x
x
Mean
x.xxx
x.xxx
Median
x.xxx
x.xxx
SD
x.xxx
x.xxx
Minimum
x.xx
x.xx
Maximum
x.xx
x.xx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Day 7
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l sch
edul
ed ti
me
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
72
of 8
2 Table 14.3.4.8.2 MAD: Summary of CURB-65 Score (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.8.
1 In
clud
e al
l sch
edul
ed ti
me
poin
ts.
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
73
of 8
2 Table 14.3.4.9.1 SD: Summary of PSI Score (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value
Change from
Baseline1
Actual
Value
Change from
Baseline1
Actual Value
Change from
Baseline1
Baseline1
n
x
x
Mean
x.xxx
x.xxx
Median
x.xxx
x.xxx
SD
x.xxx
x.xxx
Minimum
x.xx
x.xx
Maximum
x.xx
x.xx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Day 7
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l sch
edul
ed ti
me
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
74
of 8
2 Table 14.3.4.9.2 MAD: Summary of PSI Score (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.9.
1 In
clud
e al
l sch
edul
ed ti
me
poin
ts.
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
75
of 8
2 Table 14.3.4.10.1 SD: Summary of PSI Risk Class by Timepoint
Protocol: BTI-201
Safety Population
Visit
Risk Class
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Baseline1
n
xx
xx
xx
Class I
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Class II
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Class III
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Class IV
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Class V
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Day 28 / Early Termination
n
xx
xx
xx
Class I
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Class II
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Class III
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Class IV
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Class V
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
NCS = Not Clinically Significant; CS = Clinically Significant.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
76
of 8
2 Table 14.3.4.10.2 MAD: Summary of PSI Risk Class by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Pr
ogra
mm
ing
Not
e:
Repe
at T
able
14.
3.4.
10.1
In
clud
e al
l sch
edul
ed ti
me
poin
ts.
Incl
ude:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
;
Com
bine
d Ac
tive;
Com
bine
d Pl
aceb
o;
O
vera
ll
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
77
of 8
2 Table 14.3.4.11.1 SD: Summary of SOFA Score (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value
Change from
Baseline1
Actual
Value
Change from
Baseline1
Actual Value
Change from
Baseline1
Baseline1
n
x
x
Mean
x.xxx
x.xxx
Median
x.xxx
x.xxx
SD
x.xxx
x.xxx
Minimum
x.xx
x.xx
Maximum
x.xx
x.xx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Day 7
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l sch
edul
ed ti
me
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
78
of 8
2 Table 14.3.4.11.2 MAD: Summary of SOFA Score (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.11
.1
Incl
ude
all s
ched
uled
tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
79
of 8
2 Table 14.3.4.12.1 SD: Summary of MMSE Score (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Visit
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Actual Value
Change from
Baseline1
Actual
Value
Change from
Baseline1
Actual Value
Change from
Baseline1
Baseline1
n
x
x
Mean
x.xxx
x.xxx
Median
x.xxx
x.xxx
SD
x.xxx
x.xxx
Minimum
x.xx
x.xx
Maximum
x.xx
x.xx
Day 3 or 4
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Day 7
n
x
x
x
x
x
x
Mean
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Median
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
SD
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
x.xxx
Minimum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
Maximum
x.xx
x.xx
x.xx
x.xx
x.xx
x.xx
etc.
Note: SD: Standard Deviation
1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Unscheduled visits not included in post baseline assessments.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l sch
edul
ed ti
me
poin
ts.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
80
of 8
2 Table 14.3.4.12.2 MAD: Summary of MMSE Score (Summary of Actual and Change from Baseline Values) by Timepoint
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.12
.1
Incl
ude
all s
ched
uled
tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
81
of 8
2 Table 14.3.4.13.1 SD: Summary of Hospitalization
Protocol: BTI-201
Safety Population
Parameter (Kaplan-Meier Estimates)
rhu-pGSN: 6 mg/kg
(N=xx)
Placebo
(N=xx)
Overall
(N=xx)
Hospital Stay
Number of Subjects Discharged
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects not Discharged
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Length of Stay in Hospital (hours) (95% CI1)
25th Percentile
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Median
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
75th Percentile
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
ICU Stay
Number of Subjects in ICU
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects not in ICU
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Length of Stay in ICU (days) (95% CI1)
25th Percentile
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Median
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
75th Percentile
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Intubation
Number of Subjects Intubated
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Number of Subjects not Intubated
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
Length of Intubation (days) (95% CI1)
25th Percentile
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Median
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
75th Percentile
xx (xx.x, xx.x)
xx (xx.x, xx.x)
xx (xx.x, xx.x)
Note: CI = Confidence Interval; 1Brookmeyer and Crowley method (1982. Log-log transformation);
Length of stay in hospital is defined as the date and time of discharge/date of study exit (23:59 PM ) -
date and time of hospitalization admission due to CAP in hours
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Tabl
es, F
inal
V2.
0 Am
endm
ent V
1.0
2018
-12-
03
Nov
otec
h –
Stric
tly C
onfid
entia
l
Page
82
of 8
2 Table 14.3.4.13.2 MAD: Summary of Hospitalization
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Re
peat
Tab
le 1
4.3.
4.13
.1
Incl
ude
all s
ched
uled
tim
e po
ints
. In
clud
e: rh
u-pG
SN 6
mg/
kg;
rh
u-pG
SN 1
2 m
g/kg
;
rhu-
pGSN
24
mg/
kg;
Co
mbi
ned
Activ
e;
Co
mbi
ned
Plac
ebo;
Ove
rall
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
of 8
3
BT
I-201
: Moc
k Li
stin
gs: T
able
of C
onte
nts
Listings
List
ing
16.2
.1.2
.1 S
D:
Subj
ect
Disp
osit
ion
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
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.. 6
List
ing
16.2
.1.2
.2 M
AD:
Sub
ject
Dis
posi
tion
.....
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7
List
ing
16.2
.2.1
SD:
Pr
otoc
ol D
evia
tion
s ..
......
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......
.... 7
Li
stin
g 16
.2.2
.2 M
AD: P
roto
col
Devi
atio
ns ..
......
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.. 9
List
ing
16.2
.3.1
SD:
An
alys
is P
opul
atio
ns ..
......
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10
List
ing
16.2
.3.2
MAD
: A
naly
sis
Popu
lati
ons
......
......
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11
List
ing
16.2
.4.1
.1 S
D:
Demo
grap
hics
and
Base
line
Cha
ract
eris
tics
.....
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......
.. 12
Li
stin
g 16
.2.4
.1.2
MAD:
Dem
ogra
phic
s an
d Bas
elin
e Ch
arac
teri
stics
.....
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13
List
ing
16.2
.4.2
.1 S
D:
Vira
l Se
rolo
gy ...
......
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... 1
4 Li
stin
g 16
.2.4
.2.2
MAD:
Vir
al S
erol
ogy
.....
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.... 1
5 Li
stin
g 16
.2.4
.3.1
SD:
Medi
cal
Hist
ory
.....
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.... 1
6 Li
stin
g 16
.2.4
.3.2
MAD:
Med
ical
His
tory
......
......
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. 17
List
ing
16.2
.4.4
.1 S
D:
Preg
nanc
y Te
st R
esult
s ...
......
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.. 18
Li
stin
g 16
.2.4
.4.2
MAD:
Pre
gnan
cy T
est
Resul
ts ..
......
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19
List
ing
16.2
.4.5
.1 S
D:
Conf
irma
tion
of
CAP
......
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20
List
ing
16.2
.4.5
.2 M
AD:
Con
firm
atio
n of
CAP
.....
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.... 2
1 Li
stin
g 16
.2.4
.6.1
SD:
Elig
ibil
ity
Asse
ssmen
t ...
......
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.. 22
Li
stin
g 16
.2.4
.6.2
MAD:
Eli
gibi
lity
Cri
teria
......
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. 23
List
ing
16.2
.4.7
.1 S
D:
Prio
r Me
dica
tion
s ..
......
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.. 24
Li
stin
g 16
.2.4
.7.2
MAD:
Pri
or M
edic
atio
ns ..
......
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25
List
ing
16.2
.5.1
.1 S
D:
Rand
omiz
atio
n ...
......
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26
List
ing
16.2
.5.1
.2 M
AD:
Ran
domi
zati
on ...
......
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... 2
7 Li
stin
g 16
.2.5
.2.1
SD:
Stud
y Dr
ug A
dmin
istra
tion
.....
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.... 2
8 Li
stin
g 16
.2.5
.2.2
MAD:
Stu
dy D
rug
Admi
nistr
atio
n ..
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29
List
ing
16.2
.5.3
.1 S
D:
Stud
y Dr
ug I
nter
rupti
on ..
......
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30
List
ing
16.2
.5.3
.2 M
AD:
Stu
dy D
rug
Inte
rrupt
ion
......
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31
List
ing
16.2
.6.1
.1 S
D:
Indi
vidu
al p
GSN
Plasm
a Co
ncen
trat
ions
(uni
t) ..
......
......
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.... 3
2 Li
stin
g 16
.2.6
.1.2
MAD:
Ind
ivid
ual
pGSN
Plas
ma C
once
ntra
tion
s (un
it)
......
......
......
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......
.... 3
3 Li
stin
g 16
.2.6
.2.1
SD:
Indi
vidu
al Est
imat
ed
Plas
ma r
hu-p
GSN
Conce
ntra
tion
s (u
nit)
.....
......
......
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......
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......
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......
.... 3
4 Li
stin
g 16
.2.6
.2.2
MAD:
Ind
ivid
ual
Esti
mated
Pla
sma
rhu-pG
SN C
onc
entr
atio
ns (un
it)
......
......
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. 35
List
ing
16.2
.6.3
.1 S
D:
Indi
vidu
al p
GSN
Plasm
a PK
Par
amet
ers
.....
......
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.. 36
Li
stin
g 16
.2.6
.3.2
MAD:
Ind
ivid
ual
pGSN
Plas
ma P
K Pa
rame
ters
by D
ay ..
......
......
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......
.... 3
7 Li
stin
g 16
.2.6
.4.1
SD:
Indi
vidu
al Est
imat
ed
Plas
ma r
hu-p
GSN
PK Pa
rame
ters
.....
......
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.....
38
List
ing
16.2
.6.4
.2 M
AD:
Ind
ivid
ual
Esti
mated
Pla
sma
rhu-pG
SN P
K P
aram
eter
s by
Day
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 3
9
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
of 8
3
List
ing
16.2
.6.5
.1 S
D:
Anti
-rhu
-pGS
N An
tibod
ies
......
......
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40
List
ing
16.2
.6.5
.2 M
AD:
Ant
i-rh
u-pG
SN A
ntibo
dies
.....
......
......
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......
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......
.... 4
1 Li
stin
g 16
.2.6
.6.1
SD:
Biom
arke
rs ..
......
......
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......
. 42
List
ing
16.2
.6.6
.2 M
AD:
Bio
marker
s ...
......
......
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......
.... 4
3 Li
stin
g 16
.2.6
.7.1
SD:
Sput
um a
nd B
lood
Cult
ure
......
......
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44
List
ing
16.2
.6.7
.2 M
AD:
Spu
tum
and
Bloo
d Cul
ture
.....
......
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......
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......
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......
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......
.... 4
5 Li
stin
g 16
.2.7
.1.1
SD:
Adve
rse
Even
ts ...
......
......
......
......
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......
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......
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......
......
......
......
......
......
......
......
......
......
......
......
......
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......
......
......
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......
......
... 4
6 Li
stin
g 16
.2.7
.1.2
MAD:
Adv
erse
Eve
nts
.....
......
......
......
......
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......
......
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......
......
......
......
......
......
......
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......
......
......
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......
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......
......
.... 4
7 Li
stin
g 16
.2.7
.2.1
SD:
Seri
ous
Adve
rse
Event
s ...
......
......
......
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......
......
......
......
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......
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......
......
......
......
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......
......
.. 48
Li
stin
g 16
.2.7
.2.2
MAD:
Ser
ious
Adv
erse
Even
ts ..
......
......
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......
......
......
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......
49
List
ing
16.2
.7.3
.1 S
D:
Adve
rse
Even
ts L
eadin
g to
Stu
dy M
edic
ation
Dis
cont
inua
tion
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 5
0 Li
stin
g 16
.2.7
.3.2
MAD:
Adv
erse
Eve
nts
Leadi
ng t
o St
udy
Medi
catio
n Di
scon
tinu
atio
n ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 5
1 Li
stin
g 16
.2.7
.4.1
SD:
Over
all
Surv
ival
......
......
......
......
......
......
......
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......
......
......
......
......
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......
......
......
......
......
......
......
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......
. 52
List
ing
16.2
.7.4
.2 M
AD:
Ove
rall
Sur
viva
l ..
......
......
......
......
......
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......
......
......
......
......
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......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 53
Li
stin
g 16
.2.8
.1.1
.1 SD
: CB
C ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
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......
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......
......
54
List
ing
16.2
.8.1
.1.2
MA
D: C
BC ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 5
5 Li
stin
g 16
.2.8
.1.2
.1 SD
: Ab
norm
al C
BC ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
... 5
6 Li
stin
g 16
.2.8
.1.2
.2 MA
D: A
bnor
mal
CBC
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 5
7 Li
stin
g 16
.2.8
.2.1
.1 SD
: Co
agul
atio
n ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
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......
......
......
......
......
......
......
......
......
......
......
.....
58
List
ing
16.2
.8.2
.1.2
MA
D: C
oagu
lati
on ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
... 5
9 Li
stin
g 16
.2.8
.2.2
.1 SD
: Ab
norm
al C
oagu
latio
n ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 60
Li
stin
g 16
.2.8
.2.2
.2 MA
D: A
bnor
mal
Coag
ulati
on ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
61
List
ing
16.2
.8.3
.1.1
SD
: Co
mpre
hens
ive
Metab
olic
Pro
file
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
... 6
2 Li
stin
g 16
.2.8
.3.1
.2 MA
D: C
ompr
ehen
sive
Meta
boli
c Pr
ofil
e ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 6
3 Li
stin
g 16
.2.8
.3.2
.1 SD
: Ab
norm
al C
ompr
ehens
ive
Meta
boli
c Pr
ofile
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
64
List
ing
16.2
.8.3
.2.2
MA
D: A
bnor
mal
Comp
rehen
sive
Met
abol
ic P
rofil
e ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
65
List
ing
16.2
.9.1
SD:
Vi
tal
Sign
s ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
... 6
6 Li
stin
g 16
.2.9
.2 M
AD: V
ital
Sig
ns ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 67
List
ing
16.2
.10.
1 SD
: E
KG ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 68
Li
stin
g 16
.2.1
0.2
MAD:
EKG
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 69
Li
stin
g 16
.2.1
1.1
SD: P
hysi
cal
Exam
inat
ion
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
70
List
ing
16.2
.11.
2 MA
D:
Phys
ical
Exa
mina
tion
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 7
1 Li
stin
g 16
.2.1
2.1.
1 SD:
Out
come
Pre
dict
ion M
odel
s CU
RB-6
5 ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 7
2 Li
stin
g 16
.2.1
2.1.
2 MAD
: Ou
tcom
e Pr
edic
tion
Mode
ls C
URB-65
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 7
3 Li
stin
g 16
.2.1
2.2.
1 SD:
Out
come
Pre
dict
ion M
odel
s PS
I (P
ort
Score
) ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
74
List
ing
16.2
.12.
2.2
MAD
: Ou
tcom
e Pr
edic
tion
Mode
ls P
SI (
Port
Scor
e) ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 7
5 Li
stin
g 16
.2.1
2.3.
1 SD:
Out
come
Pre
dict
ion M
odel
s SO
FA S
core
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
76
List
ing
16.2
.12.
3.2
MAD
: Outc
ome
Pred
icti
on
Mode
ls S
OFA
Scor
e ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
77
List
ing
16.2
.12.
4.1
SD:
Out
come
Pre
dict
ion M
odel
s MM
SE S
core
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
78
List
ing
16.2
.12.
4.2
MAD
: Ou
tcom
e Pr
edic
tion
Mode
ls M
MSE
Scor
e ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
79
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
of 8
3
List
ing
16.2
.13.
1 SD
: C
onco
mita
nt M
edic
ation
s ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 80
Li
stin
g 16
.2.1
3.2
MAD:
Conc
omit
ant
Medi
catio
n ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 81
Li
stin
g 16
.2.1
4.1
SD: H
ospi
tali
zati
on F
ollow
-Up
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
82
List
ing
16.2
.14.
2 MA
D:
Hosp
ital
izat
ion
Follo
w-Up
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 8
3
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
of 8
3
GEN
ERAL
CO
MM
ENTS
Unl
ess o
ther
wise
stat
es, p
aram
eter
s will
be
liste
d in
alp
habe
tical
ord
er
Ch
ange
from
Bas
elin
e:
Chan
ge fr
om B
asel
ine
will
be
calc
ulat
ed a
s:
N
ames
and
ord
er o
f Tre
atm
ent G
roup
s SD
:
Coho
rt 1
: rhu
-pGS
N 6
mg/
kg;
Co
hort
1: P
lace
bo
MAD
: Co
hort
2: r
hu-p
GSN
6 m
g/kg
;
Coho
rt 2
: Pla
cebo
Coho
rt 3
: rhu
-pGS
N 1
2 m
g/kg
;
Coho
rt 3
: Pla
cebo
Coho
rt 4
: rhu
-pGS
N 2
4 m
g/kg
;
Coho
rt 4
: Pla
cebo
Nam
es o
f visi
ts
SD:
Sc
reen
ing
Da
y 1
Da
y 2
Da
y 3/
4
Day
7
Day
14
Da
y 28
/ Ea
rly T
erm
inat
ion
(Com
bine
d vi
sit fo
r saf
ety
and
effic
acy)
Uns
ched
uled
MAD
: Sc
reen
ing
Da
y 1
Da
y 2
Da
y 3
Da
y 4
Da
y 7
Da
y 14
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
of 8
3
Da
y 28
/ Ea
rly T
erm
inat
ion
(Com
bine
d vi
sit fo
r saf
ety
and
effic
acy)
Uns
ched
uled
Colu
mn
wid
ths a
nd te
xt-w
rapp
ing
may
be
alte
red
in fi
nal o
utpu
t in
orde
r to
best
pre
sent
the
data
Foot
note
s may
be
adde
d/am
ende
d if
requ
ired
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
of 8
3
Listing 16.2.1.2.1 SD: Subject Disposition
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Final Disposition
Reason for Discontinuation
Date of Study Exit
(DDMMMYYYY)
Date of Last Contact
(DDMMMYYYY)
XXX
Withdrawn
Due to Adverse Event:
AE#: XXXXXXXXXXXX
DDMMMYYYY
DDMMMYYYY
XXX
Completed
DDMMMYYYY
XXX
Completed
DDMMMYYYY
XXX
Withdrawn
Other: XXXXXXXXXXXXX
DDMMMYYYY
etc.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
of 8
3
Listing 16.2.1.2.2 MAD: Subject Disposition
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.1.2
.1 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 8
of 8
3
Listing 16.2.2.1 SD: Protocol Deviations
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Type of Deviation
Date of Deviation
(DDMMMYYYY)
Description of Deviation
XXX
ABCD
DDMMMYYYY
ABCD
ABCD
DDMMMYYYY
ABCD
…
XXX
ABCD
DDMMMYYYY
ABCD
ABCD
DDMMMYYYY
ABCD
…
XXX
ABCD
DDMMMYYYY
ABCD
ABCD
DDMMMYYYY
ABCD
…
XXX
ABCD
DDMMMYYYY
ABCD
XXX
ABCD
DDMMMYYYY
ABCD
Clinical cut-off date: DDMMMYYYY
Page x of x
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 9
of 8
3
Listing 16.2.2.2 MAD: Protocol Deviations
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
. 2.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
0 of
83
Listing 16.2.3.1 SD: Analysis Populations
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Intent-to-Treat
Population
Safety
Population
PK
Population
Per Protocol
Population
XXX
Yes
Yes
Yes
Yes
XXX
Yes
Yes
Yes
Yes
XXX
Yes
Yes
Yes
Yes
XXX
Yes
Yes
Yes
Yes
XXX
Yes
Yes
Yes
Yes
XXX
Yes
Yes
Yes
Yes
XXX
Yes
Yes
Yes
Yes
Etc.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
1 of
83
Listing 16.2.3.2 MAD: Analysis Populations
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.3.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
2 of
83
Listing 16.2.4.1.1 SD: Demographics and Baseline Characteristics
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Date of
Informed
Consent
(DDMMMYYYY)
Protocol
Version
Date of
Birth
(DDMMMYYYY)
Age at
Informed
Consent
Sex
Child
Bearing
Potential
Contraceptive
Methods
Race
Height
(cm)
Weight
(kg)
XXX
DDMMMYYYY
Amendment 1 DDMMMYYYY
xx
Male
White
xxx
xx.x
XXX
DDMMMYYYY
Amendment 1 DDMMMYYYY
xx
Female
No
White
xxx
xx.x
XXX
DDMMMYYYY
Amendment 1 DDMMMYYYY
xx
Male
White
xxx
xx.x
XXX
DDMMMYYYY
Amendment 1 DDMMMYYYY
xx
Female
Yes
Hormonal
methods
Other:
XXXXXXXXX
xxx
xx.x
etc.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
3 of
83
Listing 16.2.4.1.2 MAD: Demographics and Baseline Characteristics
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.4.1
.1 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
4 of
83
Listing 16.2.4.2.1 SD: Viral Serology
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Visit
Visit Date
(DDMMMYYYY
Test
Result
Most Recent
Viral Load
(unit)
Most Recent
CD4 Count
(unit)
XXX
Screening
DDMMMYYYY
HIV
Negative
xxxxxx
xxx.x
Hepatitis B
Surface Antigen
Negative
Hepatitis C
Negative
XXX
Screening
DDMMMYYYY
HIV
Negative
xxxxxx
xxx.x
Hepatitis B
Surface Antigen
Negative
Hepatitis C
Negative
etc.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
5 of
83
Listing 16.2.4.2.2 MAD: Viral Serology
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.4.2
.1 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
6 of
83
Listing 16.2.4.3.1 SD: Medical History
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Condition/
Body System
System Organ Class /
Preferred Term
Date of
Diagnosis
(DDMMMYYYY)
Resolution Date
(DDMMMYYYY)
Concomitant
Medication
Taken
Ongoing
XXX
XXXXXXXXXXXX/
YYYYYYYYYYYY
XXXXXXXXXX/ YYYYYYYYY/
ZZZZZZZZZ
DDMMMYYYY
DDMMMYYYY
No
No
XXXXXXXXXXXX/
YYYYYYYYYYYY
XXXXXXXXXX/ YYYYYYYYY/
ZZZZZZZZZ
DDMMMYYYY
DDMMMYYYY
Yes
Yes
…
XXX
XXXXXXXXXXXX/
YYYYYYYYYYYY
XXXXXXXXXX/ YYYYYYYYY/
ZZZZZZZZZ
DDMMMYYYY
DDMMMYYYY
No
No
XXX
XXXXXXXXXXXX/
YYYYYYYYYYYY
XXXXXXXXXX/ YYYYYYYYY/
ZZZZZZZZZ
DDMMMYYYY
DDMMMYYYY
…
XXX
XXXXXXXXXXXX/
YYYYYYYYYYYY
XXXXXXXXXX/ YYYYYYYYY/
ZZZZZZZZZ
DDMMMYYYY
DDMMMYYYY
No
No
XXX
XXXXXXXXXXXX/
YYYYYYYYYYYY
XXXXXXXXXX/ YYYYYYYYY/
ZZZZZZZZZ
DDMMMYYYY
DDMMMYYYY
No
No
Note: MedDRA Version XX.X
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
7 of
83
Listing 16.2.4.3.2 MAD: Medical History
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.4.3
.1 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
8 of
83
Listing 16.2.4.4.1 SD: Pregnancy Test Results
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Assessment Performed –
Reason Not Performed
Visit
Sample Date/ Time
(DDMMMYYY/ HH:MM)
Sample Type
Result
XXX
Yes
Screening
DDMMMYYY/ HH:MM
Serum
Negative
Day 1
DDMMMYYY/ HH:MM
Urine
Negative
Day 28 / Early
Termination
DDMMMYYY/ HH:MM
Urine
Negative
XXX
Yes
Screening
DDMMMYYY/ HH:MM
Serum
Negative
Day 1
DDMMMYYY/ HH:MM
Urine
Negative
Day 28 / Early
Termination
DDMMMYYY/ HH:MM
Urine
Negative
XXX
Yes
Screening
DDMMMYYY/ HH:MM
Serum
Negative
Day 1
DDMMMYYY/ HH:MM
Urine
Negative
Day 28 / Early
Termination
DDMMMYYY/ HH:MM
Urine
Negative
etc.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
9 of
83
Listing 16.2.4.4.2 MAD: Pregnancy Test Results
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.4.4
.1 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
0 of
83
Listing 16.2.4.5.1 SD: Confirmation of CAP
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Visit
Visit Date
(DDMMMYYY)
Was there
clinical
confirmation
of CAP
Was there
radiological
confirmation
of CAP (CXR
or CT)
Was CXR or
CT Scan
Performed:
Date
Performed
(DDMMMYYY)
CXR or CT
Scan
Findings
Date and Time of
presentation to
the hospital
(DDMMMYYY/
HH:MM)
Date and Time of
Hospitalization
Admission due to
CAP
(DDMMMYYY/
HH:MM)
Subject
Randomized
XXX
Screening
DDMMMYYYY
Yes
Yes
Yes:
DDMMMYYYY
XXXXXXXXX
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
XXX
Screening
DDMMMYYYY
Yes
Yes
Yes:
DDMMMYYYY
XXXXXXXXX
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
XXX
Screening
DDMMMYYYY
Yes
Yes
Yes:
DDMMMYYYY
XXXXXXXXX
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
etc.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
1 of
83
Listing 16.2.4.5.2 MAD: Confirmation of CAP
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.4.5
.2 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
2 of
83
Listing 16.2.4.6.1 SD: Eligibility Assessment
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Eligibility Assessment
Date
(DDMMMYYYY)
Did the patient meet all
inclusion criteria?
Inclusion
criterion
not met
Did the patient meet all
exclusion criteria?
Exclusion
Criterion
not met
XXX
DDMMMYYYY
Yes
Yes
XXX
DDMMMYYYY
Yes
Yes
XXX
DDMMMYYYY
Yes
Yes
XXX
DDMMMYYYY
Yes
Yes
XXX
DDMMMYYYY
Yes
Yes
XXX
DDMMMYYYY
Yes
Yes
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
3 of
83
Listing 16.2.4.6.2 MAD: Eligibility Criteria
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Pr
ogra
mm
ing
Not
e:
Repe
at L
istin
g 16
.2.4
.6.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
4 of
83
Listing 16.2.4.7.1 SD: Prior Medications
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Number
CM#
Drug Name/ATC3/PT
Indication
Start Date/
Stop Date
(DDMMMYYYY)
Ongoing
Dose
Unit
Frequency
Route
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
Pre-existing
condition: MH#
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
2
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
Other: YYYYYY
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
Other: YYYYYY
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
2
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
Other: YYYYYY
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
Pre-existing
condition: MH#
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
Etc.
Note: Prior medications are defined as any medication where the use was stopped prior to the first administration of the study
medication.
WHO-DD, xxxxxxxxxx
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
5 of
83
Listing 16.2.4.7.2 MAD: Prior Medications
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.4.7
.1 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
6 of
83
Listing 16.2.5.1.1 SD: Randomization
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Date /Time of
Randomization
(DDMMMYYYY/ HH:MM)
Randomization Number
Date /Time of
Emergency Unblinding
(DDMMMYYYY/ HH:MM)
Reason for Emergency Unblinding
XXX
DDMMMYYYY/ HH:MM
XXXXX
XXX
DDMMMYYYY/ HH:MM
XXXXX
XXX
DDMMMYYYY/ HH:MM
XXXXX
XXX
DDMMMYYYY/ HH:MM
XXXXX
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
DDMMMYYYY/ HH:MM
XXXXX
XXX
DDMMMYYYY/ HH:MM
XXXXX
etc.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
7 of
83
Listing 16.2.5.1.2 MAD: Randomization
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Pr
ogra
mm
ing
Not
e:
Repe
at L
istin
g 16
.2.5
.1.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
8 of
83
Listing 16.2.5.2.1 SD: Study Drug Administration
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Visit
Was Study Drug
Administered? (If
no, provide
reason)
Start Date/ Time
of Injection
(DDMMMYYYY/ HH:MM)
Stop Date/ Time
of Injection
(DDMMMYYYY/
HH:MM)
Study Drug
Administered
per Dose
Prescribed
Reason not
Successfully
Administered
Volume
Administered
(mL)
Total Duration
of Injection
(Including
Interruptions
- minutes)
XXX
Day 1
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
xx
xx
XXX
Day 1
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
xx
xx
XXX
Day 1
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
No
XXXXXXXXXXXX
xx
XXX
Day 1
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
xx
xx
XXX
Day 1
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
xx
xx
XXX
Day 1
No - XXXXXXXXX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
9 of
83
Listing 16.2.5.2.2 MAD: Study Drug Administration
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Subject
Visit
Was Study Drug
Administered? (If
no, provide
reason)
Start Date/ Time of
Injection
(DDMMMYYYY/ HH:MM)
Stop Date/ Time
of Injection
(DDMMMYYYY/
HH:MM)
Study Drug
Administered
per Dose
Prescribed
Reason not
Successfully
Administered
Volume
Administered
(mL)
Total Duration
of Injection
(Including
Interruptions
- minutes)
XXX
Day 1
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
xx
xx
Day 2
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
xx
xx
Day 3
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
No
XXXXXXXXXXXX
xx
xx
XXX
Day 1
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
xx
xx
Day 2
Yes
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
Yes
xx
xx
Day 3
No - XXXXXXXXX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
0 of
83
Listing 16.2.5.3.1 SD: Study Drug Interruption
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Visit
Interruption
Date and Time of
Interruption
(DDMMMYYYY/ HH:MM)
Date and Time of
Injection Re-start
(DDMMMYYYY/ HH:MM)
Reason for Interruption
XXX
Day 1
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
Day 1
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
2
XXX
Day 1
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
Day 1
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
Day 1
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
1 of
83
Listing 16.2.5.3.2 MAD: Study Drug Interruption
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Visit
Interruption
Date and Time of
Interruption
(DDMMMYYYY/ HH:MM)
Date and Time of
Injection Re-start
(DDMMMYYYY/ HH:MM)
Reason for Interruption
XXX
Day 1
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
Day 2
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
Day 1
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
Day 3
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
Day 1
1
DDMMMYYYY/ HH:MM
DDMMMYYYY/ HH:MM
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
2 of
83
Listing 16.2.6.1.1 SD: Individual pGSN Plasma Concentrations (unit)
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Number
Day
Date/Time
of Dose on
Dosing Day
(DDMMMYYYY/
HH:MM)
Sampling Time
Was PK
Sample
Collected?
Date of
PK Sample
Collection
(DDMMMYYYY)
Time of
PK Sample
Collection
(HH:MM)
Time
Deviation
Concen-
tration
(ng/mL)
Ratio
from Pre-
Injection
Day 1
Ratio
from Pre-
Injection
/ Placebo
Ratio
from Pre-
Injection
Comments
XXX
1
DDMMMYYYY/
HH:MM
Pre-Injection
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
YYYYYYYY
5 to 10 mins
post
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
X.XX
X.XX
2 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
8 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
12 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
16 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
24 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
XXX
1
DDMMMYYYY/
HH:MM
Pre-Injection
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
5 to 10 mins
post
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
X.XX
X.XX
YYYYYYYY
2 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
8 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
12 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
….
16 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
24 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
3 of
83
Listing 16.2.6.1.2 MAD: Individual pGSN Plasma Concentrations (unit)
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Number
Day
Date/Time
of Dose on
Dosing Day
(DDMMMYYYY/
HH:MM)
Sampling Time
Was PK
Sample
Collected?
Date of
PK Sample
Collection
(DDMMMYYYY)
Time of
PK Sample
Collection
(HH:MM)
Time
Deviation
Concen-
tration
(ng/mL)
Ratio
from Pre-
Injection
Day 1
Ratio
from Pre-
Injection
/ Placebo
Ratio
from Pre-
Injection
Comments
XXX
1
DDMMMYYYY/
HH:MM
Pre-Injection
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
YYYYYYYY
5 to 10 mins
post
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
X.XX
X.XX
2 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
8 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
12 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
16 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
24 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
2
DDMMMYYYY/
HH:MM
Pre-Injection
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
5 to 10 mins
post
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
X.XX
X.XX
YYYYYYYY
2 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
8 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
12 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
….
16 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
24 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
4 of
83
Listing 16.2.6.2.1 SD: Individual Estimated Plasma rhu-pGSN Concentrations (unit)
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Number
Day
Date/Time
of Dose on
Dosing Day
(DDMMMYYYY/
HH:MM)
Sampling Time
Was PK
Sample
Collected?
Date of
PK Sample
Collection
(DDMMMYYYY)
Time of
PK Sample
Collection
(HH:MM)
Time
Deviation
Concen-
tration
(ng/mL)
Change
from Pre-
Injection
Day 1
(Change
from Pre-
Injection)
– (Mean
Placebo
Change from
Pre-
Injection)
Comments
XXX
1
DDMMMYYYY/
HH:MM
Pre-Injection
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
YYYYYYYY
5 to 10 mins
post
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
X.XX
X.XX
2 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
8 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
12 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
16 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
24 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
XXX
1
DDMMMYYYY/
HH:MM
Pre-Injection
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
5 to 10 mins
post
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
X.XX
X.XX
YYYYYYYY
2 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
8 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
12 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
….
16 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
24 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
5 of
83
Listing 16.2.6.2.2 MAD: Individual Estimated Plasma rhu-pGSN Concentrations (unit)
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Number
Day
Date/Time
of Dose on
Dosing Day
(DDMMMYYYY/
HH:MM)
Sampling Time
Was PK
Sample
Collected?
Date of
PK Sample
Collection
(DDMMMYYYY)
Time of
PK Sample
Collection
(HH:MM)
Time
Deviation
Concen-
tration
(ng/mL)
Change
from Pre-
Injection
Day 1
(Change
from Pre-
Injection)
– (Mean
Placebo
Change from
Pre-
Injection)
Comments
XXX
1
DDMMMYYYY/
HH:MM
Pre-Injection
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
YYYYYYYY
5 to 10 mins
post
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
X.XX
X.XX
2 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
8 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
12 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
16 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
24 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
2
DDMMMYYYY/
HH:MM
Pre-Injection
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
5 to 10 mins
post
Yes
DDMMMYYYY
HH:MM
xx mins
XXX
X.XX
X.XX
YYYYYYYY
2 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
8 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
12 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
….
16 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
24 hours post
Yes
DDMMMYYYY
HH:MM
xx hours
XXX
X.XX
X.XX
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
6 of
83
Listing 16.2.6.3.1 SD: Individual pGSN Plasma PK Parameters
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Day 1
Subject
Number
AUC0-t
(unit)
AUC0-8h
(unit)
AUC0-inf
(unit)
Cmax
(unit)
Tmax
(unit)
kel
(unit)
t½
(unit)
CL/F
(unit)
Vz/F
(unit) %AUCext DN_AUC0-t DN_AUC0-8 DN_AUC0-inf
DN_Cmax
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
….
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
7 of
83
Listing 16.2.6.3.2 MAD: Individual pGSN Plasma PK Parameters by Day
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Day 1
Subject
Number
AUC0-t
(unit)
AUC0-8h
(unit)
AUC0-inf
(unit)
Cmax
(unit)
Tmax
(unit)
kel
(unit)
t½
(unit)
CL/F
(unit)
Vz/F
(unit) %AUCext DN_AUC0-t DN_AUC0-8 DN_AUC0-inf
DN_Cmax
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
….
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
8 of
83
Listing 16.2.6.4.1 SD: Individual Estimated Plasma rhu-pGSN PK Parameters
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Day 1
Subject
Number
Change from Pre-Injection
Double Delta Analysis
AUC0-t
(unit)
AUC0-8h
(unit)
Cmax
(unit)
DN_AUC0-t
DN_AUC0-8
DN_Cmax
AUC0-t
(unit)
AUC0-8h
(unit)
Cmax (unit) DN_AUC0-t
DN_AUC0-8
DN_Cmax
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
….
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
9 of
83
Listing 16.2.6.4.2 MAD: Individual Estimated Plasma rhu-pGSN PK Parameters by Day
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Day 1
Subject
Number
Change from Pre-Injection
Double Delta Analysis
AUC0-t
(unit)
AUC0-8h
(unit)
Cmax
(unit)
DN_AUC0-t
DN_AUC0-8
DN_Cmax
AUC0-t
(unit)
AUC0-8h
(unit)
Cmax (unit) DN_AUC0-t
DN_AUC0-8
DN_Cmax
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
XXX
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
xx.x
….
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
0 of
83
Listing 16.2.6.5.1 SD: Anti-rhu-pGSN Antibodies
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Li
stin
g sh
ell w
ill b
e up
date
d on
ce d
ata
tran
sfer
agr
eem
ent i
s av
aila
ble.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
1 of
83
Listing 16.2.6.5.2 MAD: Anti-rhu-pGSN Antibodies
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing 16.2.6.5.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
2 of
83
Listing 16.2.6.6.1 SD: Biomarkers
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Parameter (Unit)
Study Visit
Sample Date/ Time
(DDMMMYYYY/
HH:MM)
Actual
Value
Change from
Baseline
Reference
Ranges
High/ Low
Flag
Comments
XXX
Procalcitonin (unit)
Day 1*
DDMMMYYYY/ HH:MM
xx
xx, xx
Day 2
DDMMMYYYY/ HH:MM
xx
xx, xx
Day 3
DDMMMYYYY/ HH:MM
xx
xx
xx, xx
H
Day 4
DDMMMYYYY/ HH:MM
xx
xx
xx, xx
L
Etc.
Etc.
Note: *Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
L = Below Normal Range, H = Above Normal Range
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
3 of
83
Listing 16.2.6.6.2 MAD: Biomarkers
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing 16.2.6.6.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
4 of
83
Listing 16.2.6.7.1 SD: Sputum and Blood Culture
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Study Visit
Sputum Culture
Collected – Reason
Not Performed
Date/Time of
Collection
Results
Gram-Stains
Antigen
Detection
Immunoassay
Genomic
Diagnostic Test
Result
XXXXX
Screening
Yes
DDMMMYYYY/
HH:MM
XXXXX
Screening
Yes
DDMMMYYYY/
etc.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
5 of
83
Listing 16.2.6.7.2 MAD: Sputum and Blood Culture
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing 16.2.6.7.1
for S
D.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
6 of
83
Listing 16.2.7.1.1 SD: Adverse Events
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Number
AE#
Adverse Event Verbatim/
System Organ Class/
Preferred Term
Start Date/
Stop Date/
(DDMMMYYYY/
DDMMMYYYY)
SAE
Severity
(NCI-
CTCAE)
Relationship
to Study Drug
Relationship
to Study
Procedure
Action
Taken
with
Study
Drug
Other
Action
Outcome
TEAE
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
Yes
Grade 1
Possibly
Related
Possibly
Related
None
None Recovered /
Resolved
Yes
2
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
Yes
Grade 1
Definitely
not Related
Definitely
not Related
None
None Recovered /
Resolved
Yes
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
No
Grade 1
Definitely
not Related
Definitely
not Related
None
None Recovered /
Resolved
No
2
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
DDMMMYYYY /
Ongoing
No
Grade 1
Definitely
not Related
Definitely
not Related
Drug
withdrawn None Recovered /
Resolved
Yes
etc.
Note: TEAE = A treatment-emergent adverse event.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
7 of
83
Listing 16.2.7.1.2 MAD: Adverse Events
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing 16.2.7.1.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
8 of
83
Listing 16.2.7.2.1 SD: Serious Adverse Events
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subjec
t
Number AE#
Adverse Event Verbatim/
System Organ Class/
Preferred Term
Start Date/
Stop Date/
(DDMMMYYYY/
DDMMMYYYY)
SAE
Criteria
Severity
(NCI-
CTCAE)
Relationship
to Study
Drug
Relationship
to Study
Procedure
Action
Taken
with
Study
Drug
Other
Action
Outcome
TEAE
XXX
1
XXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
Is Life
Threatening Grade 1
Possibly
Related
Possibly
Related
None
None Recovered /
Resolved
Yes
2
XXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
Is Life
Threatening Grade 1
Definitely
not Related
Definitely
not Related
None
None Recovered /
Resolved
Yes
XXX
1
XXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
Is Life
Threatening Grade 1
Definitely
not Related
Definitely
not Related
None
None Recovered /
Resolved
No
2
XXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYY
DDMMMYYYY /
Ongoing
Is Life
Threatening Grade 1
Definitely
not Related
Definitely
not Related
Drug
withdrawn None Recovered /
Resolved
Yes
etc.
Note: TEAE = A treatment-emergent adverse event.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
9 of
83
Listing 16.2.7.2.2 MAD: Serious Adverse Events
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing 16.2.7.2.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
0 of
83
Listing 16.2.7.3.1 SD: Adverse Events Leading to Study Medication Discontinuation
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Number
AE#
Adverse Event Verbatim/
System Organ Class/
Preferred Term
Start Date/
Stop Date/
(DDMMMYYYY/
DDMMMYYYY)
SAE
Severity
(NCI-
CTCAE)
Relationship
to Study Drug
Relationship
to Study
Procedure
Action
Taken
with
Study
Drug
Other
Action
Outcome
TEAE
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
Yes
Grade 1
Possibly
Related
Possibly
Related
Drug
withdrawn
None Recovered /
Resolved
Yes
2
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
Yes
Grade 1
Definitely
not Related
Definitely
not Related
Drug
withdrawn
None Recovered /
Resolved
Yes
Drug
withdrawn
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
DDMMMYYYY/
HH:MM
DDMMMYYYY/
HH:MM
No
Grade 1
Definitely
not Related
Definitely
not Related
Drug
withdrawn
None Recovered /
Resolved
No
2
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
DDMMMYYYY /
Ongoing
No
Grade 1
Definitely
not Related
Definitely
not Related
Drug
withdrawn None Recovered /
Resolved
Yes
etc.
Note: TEAE = A treatment-emergent adverse event.
MedDRA Version xx.x
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
1 of
83
Listing 16.2.7.3.2 MAD: Adverse Events Leading to Study Medication Discontinuation
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing 16.2.7.3.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
2 of
83
Listing 16.2.7.4.1 SD: Overall Survival
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Date of First Study Drug
Administration
(DDMMMYYYY)
Event/Censoring
Date
DDMMMYYYY)
Event or Censoring
Description
Days to Event
XXX
DDMMMYYYY
DDMMMYYYY
Death
xxx
XXX
DDMMMYYYY
DDMMMYYYY
Last assessment date
xxx
XXX
DDMMMYYYY
DDMMMYYYY
Last assessment date
xxx
XXX
DDMMMYYYY
DDMMMYYYY
Death
xxx
etc.
Note: Overall Survival is defined as the difference (in days) between the
time of first study drug administration to the date of death + 1 (Include the day of the study drug administration.)
Subjects who did not die will be censored at the study exit visit.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
3 of
83
Listing 16.2.7.4.2 MAD: Overall Survival
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing 16.2.7.4.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
4 of
83
Listing 16.2.8.1.1.1 SD: CBC
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Parameter (Unit)
Study Visit
Sample Date/
Time
(DDMMMYYYY/
HH:MM)
Actual
Value
Change from
Baseline1
Reference
Ranges
High/ Low
Flag
Clinical
Significance
Abnormality
Description
XXX
Haemoglobin (unit)
Screening
DDMMMYYYY/
HH:MM
xx
xx, xx
Day 11
DDMMMYYYY/
HH:MM
xx
xx, xx
Day 2
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
H
NCS
Day 3 or 4
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
L
CS
XXXXXXXXXXXXXXX
Etc.
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant, CS = Clinically Significant.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
5 of
83
Listing 16.2.8.1.1.2 MAD: CBC
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.8.1
.1.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
6 of
83
Listing 16.2.8.1.2.1 SD: Abnormal CBC
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Parameter (Unit)
Study Visit
Sample Date/
Time
(DDMMMYYYY/
HH:MM)
Actual
Value
Change from
Baseline1
Reference
Ranges
High/ Low
Flag
Clinical
Significance
Abnormality
Description
XXX
Haemoglobin (unit)
Day 2
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
H
NCS
Day 3 or 4
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
L
CS
XXXXXXXXXXXXXXX
Etc.
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant, CS = Clinically Significant.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
7 of
83
Listing 16.2.8.1.2.2 MAD: Abnormal CBC
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.8.1
.2.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
8 of
83
Listing 16.2.8.2.1.1 SD: Coagulation
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Parameter (Unit)
Study Visit
Sample Date/
Time
(DDMMMYYYY/
HH:MM)
Actual
Value
Change from
Baseline1
Reference
Ranges
High/ Low
Flag
Clinical
Significance
Abnormality
Description
XXX
PT/INR (unit)
Screening
DDMMMYYYY/
HH:MM
xx
xx, xx
Day 11
DDMMMYYYY/
HH:MM
xx
xx, xx
Day 2
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
H
NCS
Day 3 or 4
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
L
CS
XXXXXXXXXXXXXXX
Etc.
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant, CS = Clinically Significant.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
9 of
83
Listing 16.2.8.2.1.2 MAD: Coagulation
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.8.2
.1.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
0 of
83
Listing 16.2.8.2.2.1 SD: Abnormal Coagulation
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Parameter (Unit)
Study Visit
Sample Date/
Time
(DDMMMYYYY/
HH:MM)
Actual
Value
Change from
Baseline1
Reference
Ranges
High/ Low
Flag
Clinical
Significance
Abnormality
Description
XXX
PT/INR (unit)
Day 2
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
H
NCS
Day 3 or 4
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
L
CS
XXXXXXXXXXXXXXX
Etc.
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant, CS = Clinically Significant.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
1 of
83
Listing 16.2.8.2.2.2 MAD: Abnormal Coagulation
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.8.2
.2.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
2 of
83
Listing 16.2.8.3.1.1 SD: Comprehensive Metabolic Profile
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Parameter (Unit)
Study Visit
Sample Date/
Time
(DDMMMYYYY/
HH:MM)
Actual
Value
Change from
Baseline1
Reference
Ranges
High/ Low
Flag
Clinical
Significance
Abnormality
Description
XXX
Sodium (unit)
Screening
DDMMMYYYY/
HH:MM
xx
xx, xx
Day 11
DDMMMYYYY/
HH:MM
xx
xx, xx
Day 2
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
H
NCS
Day 3 or 4
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
L
CS
XXXXXXXXXXXXXXX
Etc.
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant; CS = Clinically Significant.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
3 of
83
Listing 16.2.8.3.1.2 MAD: Comprehensive Metabolic Profile
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.8.3
.1.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
4 of
83
Listing 16.2.8.3.2.1 SD: Abnormal Comprehensive Metabolic Profile
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Parameter (Unit)
Study Visit
Sample Date/
Time
(DDMMMYYYY/
HH:MM)
Actual
Value
Change from
Baseline1
Reference
Ranges
High/ Low
Flag
Clinical
Significance
Abnormality
Description
XXX
Sodium (unit)
Day 2
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
H
NCS
Day 3 or 4
DDMMMYYYY/
HH:MM
xx
xx
xx, xx
L
CS
XXXXXXXXXXXXXXX
Etc.
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant; CS = Clinically Significant.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
5 of
83
Listing 16.2.8.3.2.2 MAD: Abnormal Comprehensive Metabolic Profile
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.8.3
.2.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
6 of
83
Listing 16.2.9.1 SD: Vital Signs
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subjec
t
Parameter
(Unit)
Assessment
Performed –
Reason Not
Performed
Study Visit
Assessment
Date
(DDMMMYYYY)
Timepoint
Time
(HH:MM)
Actual
Value
Change
from
Baseline1
Investigator’s
Overall
Interpretation If Abnormal,
specify
XXX
Systolic
Blood
Pressure
(mmHg)
Yes
Screening
DDMMMYYYY
HH:MM
xx
Normal
Yes
Day 1
DDMMMYYYY
Pre-dose1
HH:MM
xx
Abnormal NCS
XXXXXXXXX
End of
Infusion
HH:MM
xx
xx
Abnormal NCS
XXXXXXXXX
Etc.
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
NCS = Not Clinically Significant, CS = Clinically Significant
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
7 of
83
Listing 16.2.9.2 MAD: Vital Signs
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Programming Note: Repeat Listing 16.2.9.1.1 for the MAD.
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.9.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
8 of
83
Listing 16.2.10.1 SD: EKG
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subjec
t
Parameter
(Unit)
Assessment
Performed –
Reason Not
Performed Study Visit
Assessment
Date
(DDMMMYYYY) Timepoint
Time
(HH:MM) Actual
Value
Mean
Actual
Value
Mean Change
from
Baseline1
Investigator’s
Overall
Interpretation
Worst
Investigator’s
Overall
Interpretation
If
Abnormal,
specify
XXX
Heart
Rate
(unit)
Yes
Screening
DDMMMYYYY
EKG 1
HH:MM
xx
Normal
EKG 2
HH:MM
xx
xx.x
Abnormal NCS
Abnormal NCS
XXXXXXXXX
Yes
Day 11
DDMMMYYYY
EKG 1
HH:MM
xx
Abnormal NCS
EKG 2
HH:MM
xx
xx.x
Abnormal NCS
Abnormal NCS
XXXXXXXXX
Yes
Day 28 /
Early
Termination
DDMMMYYYY
EKG 1
HH:MM
xx
Abnormal NCS
EKG 2
HH:MM
xx
xx.x
xx.x
Abnormal CS
Abnormal NCS
XXXXXXXXX
etc.
etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
NCS = Not Clinically Significant, CS = Clinically Significant
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l par
amet
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
9 of
83
Listing 16.2.10.2 MAD: EKG
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.10.
1 fo
r MAD
. In
clud
e al
l par
amet
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
0 of
83
Listing 16.2.11.1 SD: Physical Examination
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Assessment
Performed –
Reason Not
Performed
Visit
Date/Time Physical
Examination
performed
(DDMMMYYYY)
Body System
Result
If Abnormal,
specify
XXX
Yes
Screening
DDMMMYYYY/ HH:MM
Skin
Normal
HEENT
Normal
….
Abnormal NCS
ZZZZZZZZZZZZ
Musculoskeletal
Abnormal NCS
ZZZZZZZZZZZZ
Yes
Day 1
DDMMMYYYY/ HH:MM
Skin
Normal
HEENT
Normal
….
Abnormal NCS
ZZZZZZZZZZZZ
Musculoskeletal
Abnormal NCS
ZZZZZZZZZZZZ
Yes
Day 2
DDMMMYYYY/ HH:MM
Skin
Normal
…
HEENT
Normal
XXX
No -
ZZZZZZZZ
….
…
Musculoskeletal
Normal
Note: NCS = Not Clinically Significant, CS = Clinically Significant
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
In
clud
e al
l tim
e po
ints
and
all
para
met
ers.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
1 of
83
Listing 16.2.11.2 MAD: Physical Examination
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.9.1
1.1
for M
AD.
Incl
ude
all t
ime
poin
ts a
nd a
ll pa
ram
eter
s.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
2 of
83
Listing 16.2.12.1.1 SD: Outcome Prediction Models CURB-65
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Study Visit
Test
Performed –
Reason Not
Performed
Visit Date
Confusion of
New Onset
Blood Urea
Nitrogen
Respiratory
Rate
(breaths/min)
Systolic/
Diastolic
BP (mmHg)
Age
(years)
CURB-65 Score
Actual
Value
Change from
Baseline1
XXXXX
Screening1
Yes
DDMMMYYYY
xx
xx (unit)
xx
xxx/ xx
xx
xx
Day 3/4
Yes
DDMMMYYYY
xx
xx (unit)
xx
xxx/ xx
xx
xx
xx
Day 7
Yes
DDMMMYYYY
xx
xx (unit)
xx
xxx/ xx
xx
xx
xx
Day 14
Yes
DDMMMYYYY
xx
xx (unit)
xx
xxx/ xx
xx
xx
xx
Day 28 /
Early
Termination
Yes
DDMMMYYYY
xx
xx (unit)
xx
xxx/ xx
xx
xx
xx
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
3 of
83
Listing 16.2.12.1.2 MAD: Outcome Prediction Models CURB-65
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.12.
1.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
4 of
83
Listing 16.2.12.2.1 SD: Outcome Prediction Models PSI (Port Score)
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Study Visit
Test Performed –
Reason Not
Performed
Visit Date
PSI Score
PSI Class
Actual Value
Change from
Baseline1
XXXXX
Screening1
Yes
DDMMMYYYY
xx
I
Day 3/4
Yes
DDMMMYYYY
xx
xx
II
Day 7
Yes
DDMMMYYYY
xx
xx
III
Day 14
Yes
DDMMMYYYY
xx
xx
IV
Day 28 / Early
Termination
Yes
DDMMMYYYY
xx
xx
V
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
5 of
83
Listing 16.2.12.2.2 MAD: Outcome Prediction Models PSI (Port Score)
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.12.
2.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
6 of
83
Listing 16.2.12.3.1 SD: Outcome Prediction Models SOFA Score
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Study Visit
Test Performed –
Reason Not Performed
Visit Date
SOFA Score
Actual Value
Change from
Baseline1
XXXXX
Screening1
Yes
DDMMMYYYY
xx
Day 3/4
Yes
DDMMMYYYY
xx
xx
Day 7
Yes
DDMMMYYYY
xx
xx
Day 14
Yes
DDMMMYYYY
xx
xx
Day 28 / Early
Termination
Yes
DDMMMYYYY
xx
xx
Etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
7 of
83
Listing 16.2.12.3.2 MAD: Outcome Prediction Models SOFA Score
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.12.
3.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
8 of
83
Listing 16.2.12.4.1 SD: Outcome Prediction Models MMSE Score
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Study Visit
Test Performed –
Reason Not Performed
Visit Date
MMSE Score
Actual Value
Change from
Baseline1
XXXXX
Screening1
Yes
DDMMMYYYY
xx
Day 3/4
Yes
DDMMMYYYY
xx
xx
Day 7
Yes
DDMMMYYYY
xx
xx
Day 14
Yes
DDMMMYYYY
xx
xx
Day 28 / Early
Termination
Yes
DDMMMYYYY
xx
xx
etc.
Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
9 of
83
Listing 16.2.12.4.2 MAD: Outcome Prediction Models MMSE Score
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.12.
4.1
for M
AD.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 8
0 of
83
Listing 16.2.13.1 SD: Concomitant Medications
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Number
CM#
Drug Name/ATC3/PT
Indication
Start Date/
Stop Date
(DDMMMYYYY)
Ongoing
Dose
Unit
Frequency
Route
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
To treat AE: AE#
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
2
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
Other: YYYYYY
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
Other: YYYYYY
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
2
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
Other: YYYYYY
DDMMMYYYY /
Ongoing
Yes
XX
Unit
YYYYYY
ZZZZZ
XXX
1
XXXXXXXXXXXXXXXXXXXXXX/
ZZZZZZZZZZZZZZZZZZZZZZ/
YYYYYYYYYYYYYYYYYYYYYY
To treat AE: AE#
DDMMMYYYY /
DDMMMYYYY
No
XX
Unit
YYYYYY
ZZZZZ
Etc.
Note: Concomitant medications are medications taken at least once after first study-drug administration.
WHO-DD, xxxxxxxxxx
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 8
1 of
83
Listing 16.2.13.2 MAD: Concomitant Medication
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Pr
ogra
mm
ing
Not
e:
Repe
at L
istin
g 16
.2.9
.13.
1 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 8
2 of
83
Listing 16.2.14.1 SD: Hospitalization Follow-Up
Protocol: BTI-201
Intent-to-Treat Population
Cohort 1: rhu-pGSN 6 mg/kg
Subject
Discharged
from
Hospital
Length of Hospital Stay
ICU Stay
Intubation
Administered
Antibiotics
Require
Vasopressors
Date and Time of
Hospitalization
Admission due to
CAP (DDMMMYYYY/
HH:MM)
Date/ Time of
Discharge/ Study
Exit
(DDMMMYYYY/
HH:MM)
Number
of
Hours
Yes/No
Number of
Days
Yes/No
Number of
Days
XXX
Yes
DDMMMYYYY/ HH:MM DDMMMYYYY/ HH:MM
xx
Yes
xx
Yes
xx
Yes
No
XXX
Yes
DDMMMYYYY/ HH:MM DDMMMYYYY/ HH:MM
xx
Yes
xx
No
No
No
XXX
Yes
DDMMMYYYY/ HH:MM DDMMMYYYY/ HH:MM
xx
No
No
No
No
XXX
No
DDMMMYYYY/ HH:MM DDMMMYYYY/ HH:MM
xx
No
No
No
No
etc.
Note: Length of stay in hospital is defined as the date and time of discharge/date of study exit (23:59 PM) -
date and time of hospitalization admission due to CAP in hours
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
List
ings
, Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 8
3 of
83
Listing 16.2.14.2 MAD: Hospitalization Follow-Up
Protocol: BTI-201
Intent-to-Treat Population
Cohort 2: rhu-pGSN 6 mg/kg
Prog
ram
min
g N
ote:
Re
peat
List
ing
16.2
.14.
1 fo
r MAD
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
of 1
8
BTI-2
01: M
ock
Figu
res:
Tab
le o
f Con
tent
s Figures
Figu
re 1
4.2.
1.1
Indi
vid
ual
pGSN
Pla
sma
Conce
ntra
tion
s (n
g/mL
) (Li
near
sca
le)
by D
ay ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 3
Fi
gure
14.
2.1.
2 In
divid
ual
pGSN
Pla
sma
Conce
ntra
tion
s (n
g/mL
) (Se
mi-l
ogar
ithm
ic)
by Da
y ...
......
......
......
......
......
......
......
......
......
......
......
......
......
4
Figu
re 1
4.2.
2.1
Indi
vid
ual
Esti
mate
d Pl
asma
rhu-pG
SN P
lasm
a Co
nce
ntra
tion
s (n
g/mL
) bas
ed o
n Ch
ange
s fr
om Pr
e-In
ject
ion
(L
inea
r sc
ale)
by
Day
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 5
Figu
re 1
4.2.
2.2
Indi
vid
ual
Esti
mate
d Pl
asma
rhu-pG
SN P
lasm
a Co
nce
ntra
tion
s (n
g/mL
) bas
ed o
n th
e Do
uble
Delt
a An
alys
is
(Lin
ear
scal
e) b
y Da
y ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.....
6 Fi
gure
14.
2.3.
1 Me
an (+
/-SD
) pG
SN P
lasm
a Con
cent
rati
ons
(ng/
mL) (
Line
ar s
cale
) by
Day
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 7
Figu
re 1
4.2.
3.2
Mean
(+
/-SD
) pG
SN P
lasm
a Con
cent
rati
ons
(ng/
mL) b
ased
on
Chan
ges
from
Pre-In
ject
ion
(Li
nea
r sc
ale)
by
Day
(Sem
i-lo
gari
thmi
c) b
y D
ay ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
. 8
Figu
re 1
4.2.
4.1
Mean
(+
/-SD
) Es
tima
ted
Plasm
a rh
u-pG
SN P
lasm
a Con
cent
rati
ons
(ng/
mL) b
ased
on
Chan
ges
from
Pre-In
ject
ion
(L
inea
r sc
ale)
by
Day
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 9
Figu
re 1
4.2.
4.2
Mean
(+
/-SD
) Es
tima
ted
Plasm
a rh
u-pG
SN P
lasm
a Con
cent
rati
ons
(ng/
mL) b
ased
on
the
Doub
le De
lta
Anal
ysis
(L
inea
r sc
ale)
by
Day
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
10
Figu
re 1
4.3.
1.1
SD:
Kap
lan-
Meie
r Pl
ot o
f Ove
rall
Sur
viva
l Ti
me ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 1
1 Fi
gure
14.
3.1.
2 MA
D: Ka
plan
-Mei
er P
lot
of Ov
eral
l Su
rviv
al T
ime
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 1
2 Fi
gure
14.
3.2.
1 SD
: Kap
lan-
Meie
r Pl
ot o
f Len
gth
of S
tay
in H
ospit
al (
hour
s) ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
... 1
2 Fi
gure
14.
3.2.
2 MA
D: Ka
plan
-Mei
er P
lot
of Le
ngth
of
Stay
in
Hospi
tal
(hou
rs)
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
... 1
4 Fi
gure
14.
3.3.
1 SD
: Kap
lan-
Meie
r Pl
ot o
f Dur
atio
n of
ICU
Sta
y ...
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
14
Figu
re 1
4.3.
3.2
MAD:
Ka
plan
-Mei
er P
lot
of Du
rati
on o
f IC
U St
ay ..
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 1
6 Fi
gure
14.
3.4.
1 SD
: Kap
lan-
Meie
r Pl
ot o
f Dur
atio
n of
Int
ubat
ion
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.... 1
7 Fi
gure
14.
3.4.
2 MA
D: Ka
plan
-Mei
er P
lot
of Du
rati
on o
f In
tuba
tion
.....
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
......
.. 18
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 2
of 1
8 GE
NER
AL C
OM
MEN
TS
Nam
es o
f Tre
atm
ent G
roup
s:
SD:
rh
u-pG
SN 6
mg/
kg.
M
AD:
rhu-
pGSN
6 m
g/kg
;
rhu-
pGSN
12
mg/
kg;
rh
u-pG
SN 2
4 m
g/kg
.
N
ames
of P
K sa
mpl
ing
times
: Da
y 1
(SD
and
MAD
) & D
ay 3
(MAD
)
Pre-
inje
ctio
n
5 to
10
min
s
2h
8h
12h
16
h
24h
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 3
of 1
8 Figure 14.2.1.1 Individual pGSN Plasma Concentrations (ng/mL) (Linear scale) by Day
Protocol: BTI-201
PK Populations
Day
1 Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Th
e x-
axis
will
repr
esen
t the
act
ual s
tudy
tim
e in
hou
rs (0
– 2
4 ho
urs)
. Th
e y-
axis
will
repr
esen
t the
pGS
N P
lasm
a Co
ncen
trat
ions
(ng/
mL)
. The
y-a
xis w
ill b
e on
the
linea
r sca
le.
All s
ubje
cts w
ill b
e re
pres
ente
d on
a si
ngle
pag
e. E
ach
dose
leve
l will
be
pres
ente
d as
a d
istin
ct li
ne ty
pe. A
sepa
rate
figu
re w
ill b
e cr
eate
d fo
r eac
h Da
y. S
D an
d M
AD
subj
ects
will
be
pres
ente
d on
the
sam
e pa
ge b
y Da
y.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 4
of 1
8 Figure 14.2.1.2 Individual pGSN Plasma Concentrations (ng/mL) (Semi-logarithmic) by Day
Protocol: BTI-201
PK Populations
Day
1 Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Th
e x-
axis
will
repr
esen
t the
act
ual s
tudy
tim
e in
hou
rs (0
– 2
4 ho
urs)
. Th
e y-
axis
will
repr
esen
t the
pGS
N P
lasm
a Co
ncen
trat
ions
(ng/
mL)
. The
y-a
xis w
ill b
e on
the
log
scal
e.
All s
ubje
cts w
ill b
e re
pres
ente
d on
a si
ngle
pag
e. E
ach
dose
leve
l will
be
pres
ente
d as
a d
istin
ct li
ne ty
pe. A
sepa
rate
figu
re w
ill b
e cr
eate
d fo
r eac
h Da
y. S
D an
d M
AD
subj
ects
will
be
pres
ente
d on
the
sam
e pa
ge b
y Da
y.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 5
of 1
8 Figure 14.2.2.1 Individual Estimated Plasma rhu-pGSN Plasma Concentrations (ng/mL) based on Changes from Pre-Injection
(Linear scale) by Day
Protocol: BTI-201
PK Populations
Day
1 Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Th
e x-
axis
will
repr
esen
t the
act
ual s
tudy
tim
e in
hou
rs (0
– 2
4 ho
urs)
. Th
e y-
axis
will
repr
esen
t the
Est
imat
ed P
lasm
a rh
u-pG
SN C
once
ntra
tions
(ng/
mL)
. The
y-a
xis w
ill b
e on
the
linea
r sca
le.
All s
ubje
cts w
ill b
e re
pres
ente
d on
a si
ngle
pag
e. E
ach
dose
leve
l will
be
pres
ente
d as
a d
istin
ct li
ne ty
pe. A
sepa
rate
figu
re w
ill b
e cr
eate
d fo
r eac
h Da
y. S
D an
d M
AD
subj
ects
will
be
pres
ente
d on
the
sam
e pa
ge b
y Da
y.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 6
of 1
8 Figure 14.2.2.2 Individual Estimated Plasma rhu-pGSN Plasma Concentrations (ng/mL) based on the Double Delta Analysis
(Linear scale) by Day
Protocol: BTI-201
PK Populations
Day
1 Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Th
e x-
axis
will
repr
esen
t the
nom
inal
stud
y tim
e in
hou
rs (0
– 2
4 ho
urs)
. Th
e y-
axis
will
repr
esen
t the
Est
imat
ed P
lasm
a rh
u-pG
SN C
once
ntra
tions
(ng/
mL)
. The
y-a
xis w
ill b
e on
the
linea
r sca
le.
All s
ubje
cts w
ill b
e re
pres
ente
d on
a si
ngle
pag
e. E
ach
dose
leve
l will
be
pres
ente
d as
a d
istin
ct li
ne ty
pe. A
sepa
rate
figu
re w
ill b
e cr
eate
d fo
r eac
h Da
y. S
D an
d M
AD
subj
ects
will
be
pres
ente
d on
the
sam
e pa
ge b
y Da
y.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 7
of 1
8 Figure 14.2.3.1 Mean (+/-SD) pGSN Plasma Concentrations (ng/mL) (Linear scale) by Day
Protocol: BTI-201
PK Populations
Day
1 Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Th
e x-
axis
will
repr
esen
t the
nom
inal
stud
y tim
e in
hou
rs (0
– 2
4 ho
urs)
. Th
e y-
axis
will
repr
esen
t the
mea
n pG
SN P
lasm
a Co
ncen
trat
ions
(ng/
mL)
per
Dos
e le
vel.
Whi
sker
s will
be
incl
uded
to re
flect
the
SDs.
The
y-a
xis w
ill b
e on
the
linea
r sc
ale.
All
trea
tmen
ts w
ill b
e re
pres
ente
d on
a si
ngle
pag
e. E
ach
dose
leve
l will
be
pres
ente
d as
a d
istin
ct li
ne ty
pe.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 8
of 1
8 Figure 14.2.3.2 Mean (+/-SD) pGSN Plasma Concentrations (ng/mL) based on Changes from Pre-Injection
(Linear scale) by Day (Semi-logarithmic) by Day
Protocol: BTI-201
PK Populations
Day
1 Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Th
e x-
axis
will
repr
esen
t the
nom
inal
stud
y tim
e in
hou
rs (0
– 2
4 ho
urs)
. Th
e y-
axis
will
repr
esen
t the
mea
n rh
u-pG
SN P
lasm
a Co
ncen
trat
ions
(ng/
mL)
per
Dos
e le
vel.
Whi
sker
s will
be
incl
uded
to re
flect
the
SDs.
The
y-a
xis w
ill b
e on
the
log
scal
e. A
ll tr
eatm
ents
will
be
repr
esen
ted
on a
sing
le p
age.
Eac
h do
se le
vel w
ill b
e pr
esen
ted
as a
dist
inct
line
type
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 9
of 1
8 Figure 14.2.4.1 Mean (+/-SD) Estimated Plasma rhu-pGSN Plasma Concentrations (ng/mL) based on Changes from Pre-Injection
(Linear scale) by Day
Protocol: BTI-201
PK Populations
Day
1 Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Th
e x-
axis
will
repr
esen
t the
nom
inal
stud
y tim
e in
hou
rs (0
– 2
4 ho
urs)
. Th
e y-
axis
will
repr
esen
t the
mea
n Es
timat
ed P
lasm
a rh
u-pG
SN P
lasm
a Co
ncen
trat
ions
(ng/
mL)
per
Dos
e le
vel.
Whi
sker
s will
be
incl
uded
to re
flect
the
SDs.
The
y-a
xis
will
be
on th
e lin
ear s
cale
. All
trea
tmen
ts w
ill b
e re
pres
ente
d on
a si
ngle
pag
e. E
ach
dose
leve
l will
be
pres
ente
d as
a d
istin
ct li
ne ty
pe.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
0 of
18
Figure 14.2.4.2 Mean (+/-SD) Estimated Plasma rhu-pGSN Plasma Concentrations (ng/mL) based on the Double Delta Analysis
(Linear scale) by Day
Protocol: BTI-201
PK Populations
Day
1 Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
Th
e x-
axis
will
repr
esen
t the
nom
inal
stud
y tim
e in
hou
rs (0
– 2
4 ho
urs)
. Th
e y-
axis
will
repr
esen
t the
mea
n Es
timat
ed P
lasm
a rh
u-pG
SN P
lasm
a Co
ncen
trat
ions
(ng/
mL)
per
Dos
e le
vel.
Whi
sker
s will
be
incl
uded
to re
flect
the
SDs.
The
y-a
xis
will
be
on th
e lin
ear s
cale
. All
trea
tmen
ts w
ill b
e re
pres
ente
d on
a si
ngle
pag
e. E
ach
dose
leve
l will
be
pres
ente
d as
a d
istin
ct li
ne ty
pe.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
1 of
18
Figure 14.3.1.1 SD: Kaplan-Meier Plot of Overall Survival Time
Protocol: BTI-201
Safety Population
Note: Overall Survival is defined as the difference (in days) between the
time of first study drug administration to the date of death + 1 (Include the day of the study drug administration.)
Subjects who did not die will be censored at the study exit visit.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
rh
u -pG
SN a
nd c
ombi
ned
Plac
ebo
trea
tmen
ts w
ill b
e pr
esen
ted
on o
ne g
raph
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
2 of
18
Figure 14.3.1.2 MAD: Kaplan-Meier Plot of Overall Survival Time
Protocol: BTI-201
Safety Population
Note: Overall Survival is defined as the difference (in days) between the
time of first study drug administration to the date of death + 1 (Include the day of the study drug administration.)
Subjects who did not die will be censored at the study exit visit.
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
rh
u -pG
SN a
nd c
ombi
ned
Plac
ebo
trea
tmen
ts w
ill b
e pr
esen
ted
on o
ne g
raph
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
3 of
18
Figure 14.3.2.1 SD: Kaplan-Meier Plot of Length of Stay in Hospital (hours)
Protocol: BTI-201
Safety Population
Note: Length of stay in hospital is defined as the date and time of discharge/date of study exit (23:59 PM ) -
date and time of hospitalization admission due to CAP in hours
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
rh
u -pG
SN a
nd c
ombi
ned
Plac
ebo
trea
tmen
ts w
ill b
e pr
esen
ted
on o
ne g
raph
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
4 of
18
Figure 14.3.2.2 MAD: Kaplan-Meier Plot of Length of Stay in Hospital (hours)
Protocol: BTI-201
Safety Population
Note: Length of stay in hospital is defined as the date and time of discharge/date of study exit (23:59 PM ) -
date and time of hospitalization admission due to CAP in hours
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
rh
u -pG
SN a
nd c
ombi
ned
Plac
ebo
trea
tmen
ts w
ill b
e pr
esen
ted
on o
ne g
raph
.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
5 of
18
Figure 14.3.3.1 SD: Kaplan-Meier Plot of Duration of ICU Stay
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
rh
u-pG
SN a
nd c
ombi
ned
Plac
ebo
trea
tmen
ts w
ill b
e pr
esen
ted
on o
ne g
raph
. Onl
y in
clud
e su
bjec
ts th
at st
ayed
in th
e IC
U.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
6 of
18
Figure 14.3.3.2 MAD: Kaplan-Meier Plot of Duration of ICU Stay
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
rh
u-pG
SN a
nd c
ombi
ned
Plac
ebo
trea
tmen
ts w
ill b
e pr
esen
ted
on o
ne g
raph
. Onl
y in
clud
e su
bjec
ts th
at st
ayed
in th
e IC
U.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
7 of
18
Figure 14.3.4.1 SD: Kaplan-Meier Plot of Duration of Intubation
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
rh
u-pG
SN a
nd c
ombi
ned
Plac
ebo
trea
tmen
ts w
ill b
e pr
esen
ted
on o
ne g
raph
. Onl
y in
clud
e su
bjec
ts th
at w
ere
intu
bate
d.
Prot
ocol
No:
BTI
-201
Do
cum
ent s
tatu
s: M
ock
EOS
Figu
res,
Fin
al V
2.0
Amen
dmen
t V1.
0 20
18-1
2-03
N
ovot
ech
– St
rictly
Con
fiden
tial
Pa
ge 1
8 of
18
Figure 14.3.4.2 MAD: Kaplan-Meier Plot of Duration of Intubation
Protocol: BTI-201
Safety Population
Clinical cut-off date: DDMMMYYYY
Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM
Prog
ram
min
g N
ote:
rh
u-pG
SN a
nd c
ombi
ned
Plac
ebo
trea
tmen
ts w
ill b
e pr
esen
ted
on o
ne g
raph
. Onl
y in
clud
e su
bjec
ts th
at w
ere
intu
bate
d.