Module 9 2024

03/09/2024

Vaccine Clinical Development Process

Early Phase

Phase IIIb/IV Licensure N=millions

Phase I N=20 – 80

Phase II N=>100s

Phase III N=1000s – 10,000s

Safety

Safety

Safety

Safety

Immunogencity Phase I : First administration in man ~ 20 subjects; usually adults

Immunogencity

Immunogencity

Evaluate safety of the vaccine Might evaluate tolerability of increasing doses of vaccine (dose escalation) Determine safety of two or more successive vaccinations Evaluate immune response

Proof of concept Phase II : Proof of Concept / Feasibility ~ 50 - 200 healthy subjects

Efficacy

Effectiveness

Dose ranging Select and justify final dose and formulation Determine the most efficient vaccination schedule (primary vaccination course) Determine most efficient route of vaccination

New indications

Safety Evaluation – Loca l

– AE Confirm the safety profile Proof of Concept (POC)

Pharmacovigilance

– Systemic

– SAE

All vaccine clinical studies have safety objectives, often as co-primary

The Organisation for Professionals in Regulatory Affairs

Leroux-Roels et al. Chapter 5 in: Garçon et al. Understanding Modern Vaccines, Perspectives in Vaccinology, Vol 1, Amsterdam, Elsevier, 2011

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Vaccine Clinical Development Process

Early Phase

Phase IIIb/IV Licensure N=millions

Phase I N=20 – 80

Phase II N=>100s

Phase III N=1000s – 10,000s

Safety

Safety

Safety

Safety

Phase III : Protective Efficacy / Safety >10,000 healthy subjects

Immunogencity Phase I : First administration in man ~ 20 subjects; usually adults

Immunogencity

Immunogencity

Effectiveness Protective efficacy : demonstrate that vaccine prevents infection / disease Immune correlate of protection Immunological bridge from lots used in large Phase III trials to final production scale Show consistency of 3 successive lots produced at industrial scale Co-administration with licensed vaccines Safety : Large safety database requested by Health Authorities New indications Pharmacovigilance

Evaluate safety of the vaccine Might evaluate tolerability of increasing doses of vaccine (dose escalation) Determine safety of two or more successive vaccinations Evaluate immune response

Proof of concept Phase II : Proof of Concept / Feasibility ~ 50 - 200 healthy subjects

Efficacy

Dose ranging Select and justify final dose and formulation Determine the most efficient vaccination schedule (primary vaccination course) Determine most efficient route of vaccination

Safety Evaluation – Loca l

– AE Confirm the safety profile Proof of Concept (POC)

– Systemic

– SAE

All vaccine clinical studies have safety objectives, often as co-primary

The Organisation for Professionals in Regulatory Affairs

Leroux-Roels et al. Chapter 5 in: Garçon et al. Understanding Modern Vaccines, Perspectives in Vaccinology, Vol 1, Amsterdam, Elsevier, 2011

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