J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 2

Abstracts AB181

MONDAY

623 Efficacy and Tolerability Of Privigen� In Clinical PracticeDr. Morna J. Dorsey, MD, MMSc, FAAAAI1, Viet Ho2,

Dr. Mohsen I. Mabudian, MD3, Pere Soler-Palac�ın4, Nerea Dom�ınguez-

Pinilla5, Dr. Robert W. Hellmers, MD, FAAAAI6, Dr. Radha Gandhi

Rishi, MD, FAAAAI6, Rahul Rishi7, Dr. Duane W. Wong, MD6,

Dr. Mikhail Rojavin, PhD8, Dr. Alphonse Hubsch9, Dr. Melvin Berger,

MD, PhD, FAAAAI8; 1Department of Pediatrics, University of California,

San Francisco, San Francisco, CA, 2Moffitt Cancer Hospital, FL, 3Beaver

Medical Group, Inc., Department of Allergy and Clinical Immunology,

Redlands, CA, 4Pediatric Infectious Diseases and Immunodeficiencies

Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain, 5Department

of Pediatrics, Hospital 12 de Octubre, Madrid, Spain, 6Arizona Allergy

Associates, Chandler, AZ, 7Arizona Allergy Associates, Phoenix, AZ,8Clinical Research and Development, CSL Behring LLC, King of Prussia,

PA, 9CSL Behring AG, Berne, Switzerland.

RATIONALE: This retrospective chart review evaluated the efficacy and

tolerability of Privigen� in patients with primary (PID) or secondary im-

munodeficiencies in clinical practice.

METHODS: Patients who had received Privigen� for >_3 months in six

clinical practices in Europe and the US were treated with individually

determined regimens. Efficacy, serum IgG levels, and safety endpoints

were assessed.

RESULTS: Seventy-two patients (52.8% male, median age 30.5 years

[range: 0.1–90.0 years]) were included. Sixty patients (83.3%) had PID, 12

(16.7%) had immunodeficiency secondary to cancer. Three infants with

severe combined immunodeficiency were analyzed separately due to

continuous hospitalization and/or exceptionally high Privigen� doses

(>_2700 mg/kg/month). In the remaining 69 patients, with a mean (6SD)

Privigen� dose of 5206182 mg/kg/month, median trough serum IgG level

was 954 mg/dL (range: 407–1581 mg/dL). Only 2 patients (2.9%) had

documented IgG levels <500 mg/dL. Nine patients (13.0%) experienced

10 serious bacterial infections over a mean of 22.3615.3 months of treat-

ment (0.080 events/patient/year), the most common being pneumonia

(n57; 10.1%). The rates for any infections and hospitalization were

1.072 events/patient/year and 3.68 days/patient/year, respectively.

However, two patients accounted for 303 hospital days. Thirteen patients

(18.8%) experienced adverse events (AEs); 10 (14.5%) had AEs at least

possibly related to study medication. The most common related AEs

were headache after infusion (n56; 8.7%), fever, and chills (n52; 2.9%

each), which are characteristic of IVIG. No related serious AEs were

reported.

CONCLUSIONS: Despite a more heterogeneous population, efficacy and

tolerability of Privigen� in clinical practicewere similar to those in clinical

trials.

624 Safety and Tolerability Of An Intravenously AdministeredAlpha1-Proteinase Inhibitor (A1PI) At An Increased InfusionRate: A Randomized, Rate Control, Placebo-Masked,Crossover Study In Healthy Adults

Adam Haeberle1, Leock Ngo1, Neil Inhaber1, David Gelmont1,

Dr. Leman Yel, MD, FAAAAI2; 1Baxter BioScience, 2Baxter BioScience,

Westlake Village, CA.

RATIONALE: A1PI (GLASSIA; Kamada Ltd) is indicated for chronic

augmentation therapy in adults with emphysema due to congenital

deficiency of alpha1-antitrypsin at an intravenous infusion rate of

0.04mL/kg/min. This study assessed the safety and tolerability of A1PI

when administered intravenously at a faster rate (0.2mL/kg/min).

METHODS: This is a prospective, randomized, rate-control, placebo-

masked, crossover study in healthy subjects aged 18-65 years. Day 1 (D1):

Subjects received intravenous A1PI 0.04mg/kg/min + placebo 0.2mg/kg/

min [A1PI/0.04] or A1PI 0.2mg/kg/min + placebo 0.04mg/kg/min [A1PI/

0.2] simultaneously through a Y-connector into 1 infusion site. D15:

Treatments were switched in the same subjects. Safety, tolerability, and

infusion changes were assessed on D1 and D15. Subject diaries (adverse

events [AEs]; concomitant medications) were collected on D29.

Laboratory assessments were performed at screening, D1, D15, D29,

and D105. Because of simultaneous A1PI and placebo administration, any

AE assessed as related to an infusion was conservatively attributed to

A1PI.

RESULTS: Thirty subjects were randomized (15/cohort) and

completed the study. The mean age was 28 years (range, 19-61),

77% were male, and mean BMI was 25.3kg/m2(range, 19.5-31.5). All

AEs (reported in 43.3% [A1PI/0.04] and 26.7% [A1PI/0.2] of subjects)

were nonserious and mild. Adverse reactions (most commonly head-

ache; dizziness) occurred in 23.3% (A1PI/0.04) and 16.7% (A1PI/

0.2) of subjects. There were no viral seroconversions after dosing.

There were no reductions in infusion rate, and no infusion interruptions

or discontinuations due to AE.

CONCLUSIONS: A1PI 0.2mL/kg/min was safe and well tolerated; faster

administration with decreased infusion duration did not lead to an

increased rate in adverse reactions.

625 Pharmacokinetic Modeling Predicts Different IgG ExposuresUsing Different IVIG-Scig Dose Conversion Factors In PatientsWith Primary Immune Deficiency

Dr. Jagdev S. Sidhu, PhD1, Dr. Mikhail Rojavin, PhD2, Dr. Melvin

Berger, MD, PhD, FAAAAI2, Dr. Martin Bexton3, Dr. Jonathan M. Edel-

man, MD2; 1Clinical Pharmacology & Early Development, CSL Ltd,

Parkville, Australia, 2Clinical Research and Development, CSL Behring

LLC, King of Prussia, PA, 3CSL Behring AG, Berne, Switzerland.

RATIONALE: Currently, US Food and Drug Administration and

European Medicines Agency recommendations suggest different methods

of calculating dosing when switching from intravenous (IVIG) to subcu-

taneous IgG (SCIG). The recommendations are based on results from small

clinical trials. To predict changes in drug exposure metrics more precisely,

we built a population pharmacokinetic (PPK) model based on a large

number of data points and simulated switching from 4-weekly IVIG

(Q4W-IVIG) to weekly SCIG using different IVIG-SCIG dose conversion

factors (DCFs).

METHODS: A PPK model based on four trials of Hizentra� and

Privigen� (including switch trials with DCFs 1.0 or 1.53) was used

to estimate exposure (steady-state area under the IgG concentration-

time curve [AUC], and IgG trough concentration [Cmin] geometric

mean ratios for IVIG/SCIG switch) using DCFs 1.30, 1.37, and 1.53.

The endogenous IgG concentration was set to 4 g/L, although setting

it to 1.5 g/L gave similar results. 300 trials of 25 patients each were

simulated.

RESULTS: Increasing DCFs applied to SCIG increased exposure

metrics with an approximately linear dose-response. For the DCFs

1.30, 1.37, and 1.53, the ratios (5th-95th percentile) were 0.94 (0.87–

1.01), 0.97 (0.90–1.04), and 1.03 (0.96–1.12) for AUC, respectively,

and 1.13 (1.05–1.23), 1.16 (1.07–1.26), and 1.23 (1.13–1.34) for Cmin,

respectively.

CONCLUSIONS: Modeling of PK parameters using large datasets can

potentially give a more accurate estimate of DCFs for IVIG/SCIG

switching than results from small trials. Our model predicted

slightly different IgG exposures with different DCFs (1.30, 1.37,

and 1.53), but all AUCs fell within the bioequivalence range of 0.80

to 1.25.