The COMBACTE, COMBACTE CARE, COMBACTE MAGNET

Consortium

Marc Bonten ECCMIDCopenhagen 26th April 2015

This research project receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115523, resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution.

Todays’ Program 13.00-13.30 Update on COMBACTE / COMBACTE-MAGNET / COMBACTE-CARE Prof.dr. Marc Bonten (UMC Utrecht) 13.30-13.45 Update on the SAATELLITE trial. Dr. Bruno Francois (CHU Limoges)/ Dr. Hasan Jafri (Astra Zeneca/MedImmune) 13.45-14.00 Update on the ASPIRE-ICU study. Prof.dr. Jan Kluytmans (UMC Utrecht)/Dr. Frank Sifakis 14.00-14.15 Update from STAT-Net Prof.dr. Stephan Harbarth (CHU Geneva) 14.15-14.30 Update on projects in preparation COMBACTE MAGNET WP5: RESCUING study Prof.dr. Leonard Leibovici (Tel Aviv University) COMBACTE MAGNET WP4A Dr. Hasan Jafri (Astra Zeneca/MedImmune)

WELCOME

Innovative Medicines Initiative (IMI): a new way to collaborate

• The largest public-private partnership in life science R&D

• IMI1 Started in 2008, ended in 2014 – 11 Calls launched

EFPIA = European Federation of Pharmaceutical

Industries and Associations

IMI: a new way of working

• Main objectives: – Accelerating the development of safer and more effective

medicines for patients in Europe – « Boosting » the biopharmaceutical sector in Europe – Create a collaborative environment for academia, industry,

SMEs, regulators, patients

• ND4BB is part of the « Action plan against the increased threats from AMR » launched by the European Commission in November 2011

ND4BB Vision: delivering a pipeline of new antibacterial agents to patients

Discovery &

Preclinical Phase I Phase II Phase III

Regulatory Review

Clinical Development

Phase IV

Discovery Commercialisation

Early Discovery

COMBACTE-MAGNET

ENABLE Translocation COMBACTE

COMBACTE-CARE

DRIVE-AB

Topic 7

Filling the pipeline

Patients

Overall Architecture of the ND4BB Programme

ND4BB – EFPIA Partners

• GSK, AZ-Medi COMBACTE

• AZ-Medi, GSK, Basilea COMBACTE-CARE

• AZ-Medi, Aicuris, Basilea, GSK, Sanofi COMBACTE-MAGNET

• GSK, Sanofi, AZ-Medi, Basilea, Janssen TRANSLOCATION

• GSK, Sanofi, AZ-Medi, Basilea ENABLE

• AZ-Medi, GSK, Astellas, Pfizer, Roche, Sanofi, DRIVE-AB

• Novartis, Basilea i-ABC

COMBACTE/COMBACTE CARE/COMBACTE MAGNET Objectives

• Create a self-sustaining antibacterial development network – Expanding research and laboratory networks – Optimal alignment of clinical trials with investigator sites – Clinical and epidemiological data

• Increase efficiency of antimicrobial drug development – Align clinical trials with cutting edge molecular mehodologies and trial

design – Deliver clinical trials with various candidate compounds from

MedImmune/Astra Zeneca, Aicures, Astra Zeneca

The 4 pillars of COMBACTE/CARE/MAGNET

CLIN-Net: a high-quality clinical research network in all European countries with certification criteria and GCP Training program

LAB-Net: a high-quality laboratory network in all European countries with assessment of existing laboratory methods, quality assessment system, specimens and strains repository

STAT-Net: a network to improve clinical trials delivery, perform advanced biostatistical and PK/PD modelling studies, evaluate novel clinical design strategies using modern biostatistical concepts

EPI-Net: a network to identify and map existing surveillance systems, to establish frameworks for data collection to support antibacterial drug development.

36 countries

157 cities

404 hospitals

728 hospital contacts

441 lab contacts

318 laboratories

CLIN- & LAB-Net in numbers

All academic partners in COMBACTE projects

COMBACTE-MAGNET

2 or 3 projects

COMBACTE-CARE

COMBACTE

The future of CLIN-Net, LAB-Net, STAT-Net and EPI-Net

The EORTC is both multinational and multidisciplinary and comprises over 300 hospitals and cancer centres in over 30 countries which include some 2,500 collaborators from all disciplines involved in cancer treatment and research.

COMBACTE (NET)

1. WP2/3: Capability building CLIN-Net/LAB-Net

2. WP4: Research activities in STAT-Net

3. WP5: Filling the gap in WP5 with new proposals (open call)

4. WP6A: Starting phase 2 -> ASPIRE-ICU study

5. WP6B: Executing SAATELITE study

Relevant ongoing activities (not including project management)

COMBACTE MAGNET (Molecules Against Gram-NEgaTive infections)

1. WP2: Capability building EPI-Net

2. WP3A: Creating alignment with COMBACTE WP6A (ASPIRE-ICU)

3. WP3B: Setting up research activities in modelling

4. WP4A: Preparation phase 2 ICU-RCT with Medi3902, preventing P. aeruginosa HAP/VAP

5. WP5: Perparing retrospective study on UTI (RESCUING study)

Relevant ongoing activities since Jan 2015 (not including project management)

WP1AProspective

observationalcohort study

WP1BMicrobiological

studies

WP1CBiomarker

studies

WP1 WP2WP2A

Phase IIa PK-PD study of ATM-AVI

ND4BB Information Center

WP3Programme management, ATM-AVI

Global Collaboration with COMBACTE and Dissemination

Joint COMBACTE & COMBACTE-CARE resource steering

group

WP2BPhase III

randomised, multicentre

study to evaluateefficacy and

safety of ATM-AVI

COMBACTE CARE (CArbapenem Resistant Enterobacteriaceae)

1. WP1: Preparation of prospective observational study

2. WP2A: Preparation of phase II PK-PD study with AZT-AVI

Relevant ongoing activities (since Mar 2015) (not including project management)

CLIN-Net charter 2 Objectives of CLIN-Net: 1. To establish and maintain a high-quality clinical research

network for new options to treat or prevent bacterial infections and in doing so, addressing the problem of antibiotic resistance in all European Union member states and affiliated countries.

2. When established to facilitate training of local investigators, certification of member sites, and maintain an up-to-date database of all its member sites.

With these 2 objectives met CLIN-Net will be able to facilitate rapid feasibility assessment and site selection for clinical studies followed by a high quality execution of the trials.

CLIN-Net charter

Sustainability of CLIN-Net CLIN-Net is funded by IMI JU for a period of 7 years. During this funding period CLIN-Net aims to become a self-sustaining not-for-profit organization.

Networks currently involved

● Spain: REIPI, CIBERES, ACIP ● France: RENARCI, CRICS, Outcome-REA ● Germany: DZIF, SepNet/CSCC, COCTIG, CAP-NETZ ● Belgium: BELGIMIAN, BELGISEARCH ● Sweden: HOPE ● Greece: HERCOID, ICU-network ● Hungary: HSCMID ● Israel: Unnamed ● Italy: ITACA, GiVITI ● Portugal: SUBLIME ● Netherlands: CLIN-Net /SION Netherlands ● International: PENTA, AO-foundation

CLIN-Net as a network of networks • Coordination by country coordinators / teams • Agreed coordinators / teams for networks in

– Spain (3 networks) – Germany (4 networks) – France (2 networks) – The Netherlands

• New networks (being) set up by CLIN-Net: – Portugal, SUBLIME – Hungary, HSCMID – Czech Republic (in progress) – Bulgaria (in progress) – Slovakia ( in progress) – Romania (in progress)

CLIN-Net PMO

Coordinator network A

LAB-Net PMO

Coordinator network B Coordinator network C

CLIN-Net PMO

Coordinator 1 subnetwork / specialty

LAB-Net PMO

Coordinator 2 subnetwork / specialty

Coordinator 3 subnetwork / specialty

Regional team Main contact person LAB-Net coordinator

Soon: CLIN-Net international board • Forum of coordinators national networks

– Necessary step towards self-sustainability

• Fall 2015: face-to-face meeting – Coordinators of established national networks

• Minimum requirements will apply

– Topics: • Structure of CLIN-Net, certification requirements, GCP-

requirements, form and frequency of meetings, processes to recruit sites, processes to submit research proposals, etc…

– Pre-meeting for…

1st CLIN-Net International board meeting • Presumptive date: Monday January 23rd, 2016 • National coordinators • Agenda:

• Update on studies in progress, study proposals • Roles and tasks within CLIN-Net, structure of CLIN-Net • Site requirements, certification, GCP, etcetera • CLIN-Net agenda towards the future

Milestone: CLIN-Net Data management

• CLIN-Net has developed a database containing information on hospital organization and facilities, experience in clinical trials, interest in clinical trials, antibiotic policies and infection prevention of all hospitals in CLIN-Net.

• All individual databases from various COMBACTE questionnaires

have now been integrated.

Why is this useful?

CLIN-Net Site Selection

Major improvement for identifcation of suitable sites for clinical studies!

1. Study-team needs sites for participation

2. Access to COMBACTE Metadatabase

3. Shortened feasibility process

e.g.: Min 500 beds; 24/7 pharmacy; >50 VAPs per year ; central ICD-10 coding ; max 60 days for budgets

- Select (existing) questions from different categories ór search for questions using keywords - Add few additional study specific questions

COMBACTE : - makes pre-selection of sites based on previously

obtained data - creates feasibility questionnaire from selected

questions - Investigators receive prefilled questionnaires and

update where necessary - CLIN-Net database is kept up to date

CLIN-NET GCP COURSE

Objective WP2: “To help member sites in reaching and maintaining full GCP / ICH compliance”

Adequate execution of a trial is essential in maintaining our network of investigators that can perform high quality clinical trials.

Main problem with GCP: investigators generally consider it tedious to read through

CLIN-NET GCP COURSE

Our challenge: Build a GCP Course that investigators find interesting to participate in. Progress 2014: Partnership was established with elevate Health, a company specialized

in online courses, to develop an interesting, high-quality, and online GCP Course.

Course was developed, and finished in May 2014. From June on the first CLIN-Net investigators followed the course

CLIN-NET GCP COURSE

In 2014, an 8.2 (on a scale from 1-10) average was given for the course.

In addition, 55% of the participants found the learning materials to be ‘very good’, 36% ‘good’ and 9% found the content of the course ‘neither good nor bad’.

Response: “The whole course was an enjoyable experience, where boring items were presented in an amusing way. So, I have nothing to suggest, just to keep it up. Thank you for your help.” Response: “The course was educative and at the same time an amusing experience that I really enjoyed. I'm grateful for everything I learned. I strongly recommend the course to all researchers and doctors involved in research.”

CLIN-NET GCP COURSE

Goals for 2015

Promote the GCP course by means of newsletters, the COMBACTE website, e-mail, congresses and during the feasibility process of clinical trials within CLIN-Net.

Emphasize investigators, coordinators and COMBACTE partners that investigators need valid GCP accreditation to participate in CLIN-Net trials.

Explore other (national) GCP courses that can be accepted as equal qualification.

To enroll in the COMBACTE GCP course or for more information contact us at: combacte-gcp@combacte.com.

www.combacte.com

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WEBSITE ACTIVITY

UPCOMING EVENTS IN 2015 October: GCP training for Investigators in Eastern Europe October • 2 day GCP Training • Participants will need to pass the online training first • International and local trainers • Different countries, at later stages also in Southern Europe • Collaboration with EF-GCP

The COMBACTE “pipeline”

ECCMID-COMBACTE Symposium Challenges in the clinical development of new antibacterial agents

Tuesday 28 Apr 2015, 13:30 - 15:30 h, Hall B News on the development of antibodies for the prevention of severe bacterial infections Jan A.J.W. Kluytmans (Breda, Netherlands) Development of drugs for treatment of abdominal infections caused by multidrug-resistant pathogens Philippe Montravers (Paris, France) Which changes in the regulatory landscape will be most useful? Marco Cavaleri (London, United Kingdom) Alternative trial designs Stephan J. Harbarth (Geneva, Switzerland)

VISIT US AT BOOTH NUMBER