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

nonevaluable or having serological evidence of prior infection with SARS-CoV-2,
potentially making them immune to further infection. Dependent upon the evolution of the
pandemic, it is possible that the COVID-19 attack rate may be much higher, in which 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.

In Phase 3, approximately 2000 participants are anticipated to be 12 to 15 years of age. A
random sample of 250 participants will be selected for each of the 2 age groups (12 to 15
years and 16 to 25 years) as an immunogenicity subset for the noninferiority assessment.
With the standard deviation and observed GMT difference assumed in the power analysis
below, 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 of adolescents to 16- to
25-year-olds in terms of neutralizing antibody GMR, 1 month after the second dose
(see Table 4).

Table 4. Power Analysis for Noninferiority Assessment

b
Criteria Standard Assumed Number of Power
Deviation Observed GMT Evaluable
(Log Value) Difference (Log Participants per
a
Scale) Age Group
Lower limit of 95% 0.623 -0.2 200 90.8%
CI for GMR
(12-15/16-25)
>0.67
Abbreviation: GMR = geometric mean ratio.
a. Reference: 1 month after Dose 2, BNT162b2 (30 µg), 18- to 55-year age group (C4591001 Phase 1,
N=12). Calculation may be updated if additional information becomes available to better estimate the
standard deviation.
b. At 0.05 alpha level (2-sided).

For safety outcomes, Table 5 shows the probability of observing at least 1 AE for a given
true event rate of a particular AE, for various sample sizes. For example, if the true AE rate
is 10%, with 12 participants in a vaccine group, there is 72% probability of observing at least
1 AE.

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