Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age

Abstract

Background: Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age.

Methods: A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed.

Results: During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3).

Conclusions: A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Copyright © 2021 Massachusetts Medical Society.

Figures

Figure 1. Screening, Randomization, and Vaccine and Placebo Administration among 5-to-11-Year-Old Children in the Phase 1 Study and the Phase 2–3 Trial.

Participants who discontinued the vaccination regimen could remain in the study. In the phase 2–3 trial, reasons for not receiving the first dose included withdrawal (14 children), no longer meeting eligibility criteria (2 children), and protocol deviation (1 child). Discontinuations or withdrawals after the first dose were due to a decision by the parent or guardian or by the participant, except one, for which the reason was classified as “other.” In the phase 2–3 trial, one participant who was randomly assigned to receive placebo was administered BNT162b2 in error for both doses. Therefore, 1518 participants received dose 1 of BNT162b2 and 750 participants received dose 1 of placebo.

Figure 2. Local Reactions and Systemic Events Reported in the Phase 2–3 Trial within 7 Days after Injection of BNT162b2 or Placebo.

Panel A shows local reactions and Panel B shows systemic events after the first and second doses in recipients of the BNT162b2 vaccine (dose 1, 1511 children; dose 2, 1501 children) and placebo (dose 1, 748 or 749 children; dose 2, 740 or 741 children). The numbers refer to the numbers of children reporting at least one “yes” or “no” response for the specified event after each dose; responses may not have been reported for every type of event. Severity scales are summarized in Table S5; fever categories are designated in the key. The numbers above the bars are the percentage of participants in each group with the specified local reaction or systemic event. 𝙸 bars represent 95% confidence intervals. One participant in the BNT162b2 group had a fever of 40.0°C after the second dose.

Figure 3. Vaccine Efficacy in Children 5 to 11 Years of Age.

The graph represents the cumulative incidence of the first occurrence of Covid-19 after the first dose of vaccine or placebo. Each symbol represents cases of Covid-19 starting on a given day. Results shown in the graph are all available data for the efficacy population, and results shown in the table are those for the efficacy population that could be evaluated (defined in Table S1). Participants without evidence of previous infection were those who had no medical history of Covid-19 and no serologic or virologic evidence of past SARS-CoV-2 infection before 7 days after the second dose (i.e., N-binding serum antibody was negative at the first vaccination visit, SARS-CoV-2 was not detected in nasal swabs by nucleic acid amplification test at the vaccination visits, and nucleic acid amplification tests were negative at any unscheduled visit before 7 days after the second dose). The cutoff date for the efficacy evaluation was October 8, 2021. Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point. The time period for Covid-19 case accrual was from 7 days after the second dose to the end of the surveillance period. The 95% confidence intervals for vaccine efficacy were derived by the Clopper–Pearson method, adjusted for surveillance time.