AMA1-DiCo clinical trial phase Ia/ Ib: challenges and status

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1 AMA1-DiCo clinical trial phase Ia/ Ib: challenges and status Pierre Loulergue, MD CIC de Vaccinologie Cochin-Pasteur, Paris EVI Rendez-vous Heidelberg 04/12/2013

2 The Clinical Research Center in Vaccinology (Centre d Investigation Clinique en Vaccinologie), Cochin Hosp., Paris An original and efficient structure, dedicated to clinical research in the field of vaccinology (vaccinal trials). Ø The Clinical Research Center in Vaccinology Cochin Pasteur (CIC BT505) is the sole French clinical research center dedicated to vaccinal research. Ø CIC BT505 was created in 2005,and is re-evaluated every 4 years since then. Ø The center is administrated by Inserm and is located inside a university hospital in Paris. Ø The center is entirely dedicated to the : w conception w organization, w coordination w implementation of the clinical researches. Ø The CIC BT505 carries out clinical studies in the context of preventive and therapeutic vaccines. Besides, it promotes the development of new vaccine approaches emerging from fundamental research.

3 The AMA1-DiCo trial Vaccine candidate: recombinant Pichia pastoris AMA1- DiCo Adjuvants: GLA-E and Alhydrogel Target population: healthy malaria non-exposed European malaria exposed African adults Methodology: phase I, randomised, double-blind, multicentre trial

4 PARTNER INVLVED EVI Funder Germany IDRI Adjuvant: Gla-E UA INERM C10 Methodology and statistics France INERM et INERM Transfert ponsor France CIC Cochin Coordination and Clinical center France BPRC Vaccine candidate inventor The Netherlands Technology transfert Immunomonitoring France CIC R. Debré Data management & Monitoring France African clinical center CNRFP Burkina Faso ther providers IB, shipments,

5 Hurdles ponsor is not the funder, nor the inventor everal (8) contracts between the parties ponsor s internal scientific validation process: 3 submissions (May 2012-May 2013) ANM (French drug agency): 1 presubmission, 1 submission, 2 revisions Ethics comittee: 1 submission Multiplicity of actors: challenging to warn everyone and get responses in a short period of time (48h) Challenging questions: GLA-E manufacturing process, animal model

6 What we went through since Dec Agreement on the study design ( 66 volunteers; placebo) ponsor s internal scientific validation process (questions on the G/NG criteria; choice of adjuvants) ignature of many contracts between the partners Intellectual property matters (IDRI) Regulatory authorities (France) approval Visit to the african clinical site

7 And eventually tudy initiation visit: 6th december 2013 First enrollment: 6th january 2014 First immunization: 20th january 2014

8 Design of the trial Phase Ia/Ib, Randomised, ingle-blind, Multicentric trial. Number of centers: 2 (France + Burkina Faso) Number of cohorts: 2 Total = 66 healthy volunteers Cohort A (France) : 30 Group 1A (15) 50µg AMA-1DiCo + Alhydrogel (0.85 mg Al3+per dose) Group 2A (15) 50 µg AMA-1 DiCo + GLA-E (2.5 µg GLA per dose) Cohort B (Burkina Faso) : 36 Group 1B (18) 50 µg AMA-1DiCo + GLA-E (2.5 µg GLA per dose ) Group 2B (18) Placebo (saline solution) 3 immunizations (IM route) at D0, W4, W26 Duration of participation: 52 weeks (10 visits)

9 G / N G criteria Adjuvants Alhydrogel GLA-E Adults yrs Phase Ia/Ib Europe 1 Africa 1 formulation AMA-1 DiCo 1 dosage G: ne week after the 1st immunisation of the last volunteer of the European group, if no subject had an AE related to vaccination and less than 50% subjects had any Grade 3 adverse reaction persisting at Grade 3 for > 48 hours N G: topping rule for GLA-E or Alhydrogel * use in cohort B: Any AE related to vaccination or 50% of subjects had Grade 3 adverse reaction persisting at Grade 3 for > 48 hours during the 7 follow-up days Criteria validated by an independent data monitoring board before starting in Burkina Faso

10 CLINICAL TRIAL PHAE Ia/Ib DEIGN Cohort A (Europe) Group 1A N=15 AMA-1 DiCo 50µg Alhydrogel Cohort A (Europe) Group 2A N=15 AMA-1 DiCo 50µg GLA-E Wee k cr cr Vaccination Period Follow-up Cohort B (Africa) Group 1B N=18 AMA-1 DiCo 50µg GLA-E or Alhydrogel cr Vaccination Period Follow-up Cohort B (Africa) Group 2B N=18 Placebo = Vaccination cr=screening period afety bservation Wee k afety Review and Approval by DMB cr

11 Conclusion till not easy Many partners, differents countries, deadlines Legal and economic matters Necessiting a lot of work/open-mindness/ conciliation/pugnacity/diplomacy tart date: 06 Jan 2014

12 Acknowledgements EVI: ophie Houard, Celine Dutruel, dile Leroy BPRC: Ed Remarque Inserm: JC Hebert, onia Gueguen, Claire Levy-Marchal CNRPF: odiomon irima, Adama Gansane Inserm C10: Christine Durier, JP Aboulker CIC: Leila Kara, Lorine Trouchaud, dile Launay

13 Danke schön!