MenAfriVac clinical development

Transcription

1 MenAfriVac clinical development Meningitis Vaccine Project Closure Conference Addis Ababa, Ethiopia 22 February 2016 Dr Marie-Pierre Preziosi

2 % Free Saccharide % Free Saccharide % Free Saccharide of MenAfriVac through development % Free saccharide: Bulk conjugate & final fill ph I ph I-0402 ph I-0403 ph II-0601 Study Lot number Study4-10 ph III-lot1 ph III-lot2 ph III-lot3 Final fill Bulk conjugate Lyophilisation did not cause an increase in % free saccharide. Levels low throughout at time of release. Final Fill: Free Saccharide Good correlation between NIBSC and manufacturer s values Lot number NIBSC SII

3 1/Bactericidal Titre (+/- 95% CI) dev bulk Ph I - lot 1 Ph I - lot 2 Ph I - lot 3 Ph II Study 3 Study Study 4-5 Study 4-10 Ph III - Lot 1 Ph III - Lot 2 Ph III - Lot 3 Geometric IgG Titre (+/- 95% CI) dev bulk Ph I - lot 1 Ph I - lot 2 Ph I - lot 3 Ph II Study 3 Study Study 4-5 Study 4-10 Ph III - Lot 1 Ph III - Lot 2 Ph III - Lot 3 Pre-clinical immunogenicity Correlation established at dose 2 between total IgG and functional Ab Total IgG Response - ELISA Bactericidal IgG Response -SBA Vaccine - 2 Doses

4 Clinical Development Strategy, Relevant Questions?

5 Clinical Development Questions Problem development rationale Scientific background, epidemiology, justification for vaccine development, antibody titers and protection, clinical development program, Good Clinical Practice Biopharmaceutics Formulation of the vaccine, differences between the to-be-marketed formulation and formulations used in clinical studies (clinical data with the final formulation of the vaccine produced at the intended scale for commercial use), bio-analytical / analytical methods used for human studies (choice of assays) Clinical pharmacology (immunogenicity studies) Efficacy (immunogenicity, persistence, memory) study by study and across studies, response to carrier protein, concomitant vaccines Safety Database, population, limitations (risk management plan), adverse events (reactogenicity including immediate reactions, AEs, SAEs) study by study and across studies Benefit and risk conclusions Overall plan to address relevant questions, efficacy, safety, special populations

6 MenAfriVac Clinical Development Program Regulatory Perspective Non-inferiority to the reference evaluation of the efficacy of MenAfriVac based on its ability to induce levels of serum bactericidal antibodies (SBA) not inferior to those induced by a licensed meningococcal polysaccharide (Ps) vaccine Valid surrogate marker of protection presence of SBA confers protection, efficacy studies not required for licensing meningococcal conjugate vaccines (1) Primary criterion in determining immune non-inferiority percentage of vaccinees having a 4-fold or greater increase in SBA titer after receiving MenAfriVac as compared with vaccinees receiving the reference meningococcal Ps vaccine 1. WHO technical report series WHO/BS/ Recommendations to assure the quality, safety and efficacy of group A meningococcal conjugate vaccines

7 MenAfriVac clinical development 1 to 29-year-old indication Infant indication Expanding Safety Database 6000 subjects Phase III Mali 1-29 year-olds Feb10-Jan11 Phase II Mali Infants Feb12-Jul13 Confirming Schedule Expanding Safety Database 1500 subjects Confirming Lot Consistency 830 subjects Phase III India 5-10 year-olds Jan- Jun10 Phase II Ghana Infants Nov08-Jul12 Dose Selection Schedule Evaluation Immune Persistence 1200 subjects Safety Immunogenicity Memory Immune Persistence 600 subjects Safety Immunogenicity Immune Persistence Carriage 1240 subjects Phase II/III India 2-10 year-olds Aug07-Nov08 Phase II/III Senegal Mali The Gambia 2-29 year-olds Aug07-Apr09 Phase II Mali The Gambia month-olds Sep06-Apr09 Immune Persistence 4 years after 1 dose 900 subjects Immune Persistence 5 years after 1 dose 600 subjects Safety Immunogenicity Immune Persistence Phase I India year-olds Aug05-Oct06 DCGI Submission WHO Submission DCGI Export License WHO Pre- Qualification DCGI License for India DCGI submission & infant license variation Jan Jun Jan Jun Jan Jun Jan Jun Jan Jun Jan Jun Jan Jun Jan Jun Jan Jun Jan Jun

8 MenAfriVac Clinical Development Program Summary Implementation Expert support (statistics, serology, carriage, pharmacovigilance) Expert review and continuous monitoring of clinical program Expert Panel (pharma and clinical) Project Advisory Group (clinical and introduction) Independent scientific peer review of all study protocols Multiple ethical clearance (IRBs, IECs in country & at study sites) Multiple regulatory clearance (Indian and African Authorities) Conduct of trials according to ICH/GCP, regulatory requirements Comprehensive GLP serologic testing at reference laboratories Independent GCP audits and regulatory inspections of trial sites

9 MenAfriVac, licensure and WHO prequalification Common Regulatory Dossier? License a MenA conjugate vaccine for the African meningitis belt In order to fulfill the regulatory requirements of countries and WHO Indication Text Marketing Authorization in the country of manufacture Drug Controller General (India) WHO prequalification Registration in countries of the African meningitis belt 1 to 29 year-olds December 2009 June 2010 August ongoing Infants license variation 3 to 24 month-olds November 2014 December 2014 Ongoing

10 Teams, Partners, Advisors Commitment to Rigor and Excellence Communication, Collaboration, Mutual Learning Keeping Pace and Success