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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591001

power to conclude true VE >30%. This would be achieved with a total 43,998 participants
(21,999 vaccine recipients), based on the assumption of a 1.3% per year incidence in the
placebo group, accrual of 164 primary-endpoint cases within 6 months, and 20% of the
participants being nonevaluable. If the attack rate is much higher, case accrual would be
expected to be more rapid, enabling the study’s primary endpoint to be evaluated much
sooner. The total number of participants enrolled in Phase 2/3 may vary depending on the
incidence of COVID-19 at the time of the enrollment, the true underlying VE, and a potential
early stop for efficacy or futility.

VE will be evaluated using a beta-binomial model and the posterior probability of VE being
>30% will be assessed.

In Phase 3, up to approximately 2000 participants are anticipated to be 12 to 15 years of age.
Noninferiority of immune response to prophylactic BNT162b2 in participants 12 to 15 years
of age to response in participants 16 to 25 years of age will be assessed based on the GMR of
SARS-CoV-2 neutralizing titers using a 1.5-fold margin. A sample size of 200 evaluable
participants (or 250 vaccine recipients) per age group will provide a power of 90.8% to
declare the noninferiority in terms of GMR (lower limit of 95% CI for GMR >0.67).

The primary safety objective will be evaluated by descriptive summary statistics for local
reactions, systemic events, AEs/SAEs, and abnormal hematology and chemistry laboratory
parameters (Phase 1 only), for each vaccine group. A 3-tier approach will be used to
summarize AEs in Phase 2/3.

Except for the objective to assess the noninferiority of immune response in participants 12 to
15 years of age compared to participants 16 to 25 years of age, the other immunogenicity
objectives will be evaluated descriptively by GMT, GMC, GMFR, percentage of participants
with ≥4-fold rise, percentage of participants with ≥ specified threshold, and GMC ratio, and
the associated 95% confidence intervals (CIs), for SARS-CoV-2 neutralizing titers,
S1-binding IgG levels, and/or RBD-binding IgG levels at the various time points.

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