A Phase 1/2/3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate Against COVID-19 in Healthy Children
Condition: SARS-CoV-2 Infection, COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This is a Phase 1/2/3 study in healthy children.

      Dependent upon safety and/or immunogenicity data generated during the course of this study,
      and the resulting assessment of benefit-risk, the safety, tolerability, and immunogenicity of
      BNT162b2 in participants <6 months of age may subsequently be evaluated.
    

Detailed description: 
      Phase 1 Dose-Finding

      Is the open-label dose-finding portion of the study that will evaluate safety, tolerability,
      and immunogenicity of BNT162b2 administered on a 2-dose (separated by approximately 21 days)
      schedule in up to 3 age groups (participants ≥5 to <12 years, ≥2 to <5 years, and ≥6 months
      to <2 years of age).

      Dose finding is being initiated in this study in participants ≥5 to <12 years of age based on
      the acceptable blinded safety assessment of the 30-µg dose in 12- to 15-year-olds in the
      C4591001 study.

      The purpose of Phase 1 is to identify preferred dose level(s) of BNT162b2 from up to 3
      different dose levels in each age group.

      Dependent upon safety and/or immunogenicity data generated during the course of this study,
      it is possible that dose levels may not be started, may be terminated early, and/or may be
      added with dose levels below the lowest stated dose.

      Update as part of protocol amendment 6: All participants will receive a third dose of
      BNT162b2. For participants ≥6 months to <5 years, the third dose will occur at least 8 weeks
      after the second dose. In participants ≥5 to <12 years, the third dose will occur at least 6
      months after the second dose. The interval between the second and third doses will be based
      on the participant's age at the time of enrollment. The dose level of the third dose of
      BNT162b2 will be based on age at the time of vaccination: participants <5 years of age at the
      time of the third dose will receive the 3-µg dose level, participants ≥5 to <12 years of age
      at the time of the third dose will receive the 10-µg dose level, and participants ≥12 years
      of age at the time of the third dose will receive the 30-µg dose level.

      Participants will have blood drawn prior to both Dose 1 and Dose 2 and 7 days after Dose 2 to
      assess immunogenicity to determine the selected BNT162b2 dose level for Phase 2/3.
      Participants will also have blood drawn prior to Dose 3 and 1, 6, and 12 months after Dose 3.

      Phase 2/3 Selected-Dose

      Is the portion of the study that will evaluate the safety, tolerability, and immunogenicity
      in each age group at the selected dose level from the Phase 1 dose-finding portion of the
      study. Efficacy will be evaluated within or across age groups in which immunobridging is
      successful, depending on accrual of a sufficient number of cases in those age groups.

      Participants will have blood drawn at baseline prior to Dose 1 and 6 months after Dose 2.
      Immunobridging to participants 16 to 25 years of age in the C4591001 study will be based on
      immunogenicity data collected at (1) baseline and 1 month after Dose 2 and (2) baseline and 1
      month after Dose 3. The persistence of the immune response will be based on immunogenicity
      data collected in participants at (1) baseline and 1 and 6 months after Dose 2 and (2)
      baseline and 1, 6, 12, and 18 months after Dose 3. In addition, efficacy against confirmed
      COVID-19 and against asymptomatic infection will also be assessed in participants ≥5 to <12
      years of age.

      At designated US sites, an additional optional whole blood sample of approximately 10 mL will
      be obtained prior to Dose 1 and at 7 days and 6 months after Dose 2 from up to approximately
      60 participants ≥10 years of age. Additional samples will be obtained prior to Dose 3 and 1
      month after Dose 3 (original BNT162b2 group only). These samples will be used on an
      exploratory basis to investigate the postvaccination cell-mediated immune response at these
      time points.

      At the 6-month follow-up visit, all participants will be unblinded. Participants who
      originally received placebo will be offered the opportunity to receive BNT162b2 as part of
      the study. Participants who originally received placebo and become eligible for receipt of
      BNT162b2 or another COVID-19 vaccine according to local or national recommendations prior to
      the 6 month follow-up visit (Visit 5 or 405) (detailed separately and available in the
      electronic study reference portal) will have the opportunity to receive BNT162b2 (10 µg or 3
      µg) based on age at the time of vaccination.

      Update as part of protocol amendment 6: All participants will receive a third dose of
      BNT162b2. For participants ≥6 months to <5 years, the third dose will occur at least 8 weeks
      after the second dose. In participants ≥5 to <12 years, the third dose will occur at least 6
      months after the second dose. The interval between the second and third doses will be based
      on the participant's age at the time of enrollment. The dose level of the second and third
      doses of BNT162b2 will be based on age at the time of vaccination: participants <5 years of
      age at the time of the second/third dose will receive the 3-µg dose level, participants ≥5 to
      <12 years of age at the time of the second/third dose will receive the 10-µg dose level, and
      participants ≥12 years of age at the time of the second/third dose will receive the 30-µg
      dose level.

      Phase 2/3 Obtaining Serum Samples for Potential Troponin I Testing

      If testing of troponin I levels in individuals who did not receive BNT162b2 indicates that
      troponin I level could be a reliable indicator of potential subclinical myocarditis,
      obtaining serum samples for potential troponin I testing during the period of increased risk
      of clinical myocarditis may help characterize the absence/presence and frequency of
      subclinical myocarditis. To assess, an additional group of participants will be included: ≥5
      to <12 years: randomized 2:1 to receive BNT162b2 10 µg or placebo, and ≥12 to <16 years of
      age: open-label receipt of BNT162b2 30 µg.

      Update as part of protocol amendment 7: All participants will receive a third dose of
      BNT162b2. For all participants (≥5 to <12 and ≥12 to <16 years of age), the third dose will
      occur at least 5 months after Dose 2.

      The dose level of the second and third doses of BNT162b2 will be based on age at the time of
      vaccination: participants ≥5 to <12 years of age at the time of the second/third dose will
      receive the 10-µg dose level, and participants ≥12 years of age at the time of the
      second/third dose will receive the 30-µg dose level.

      Update as part of protocol amendment 8: The Lower-Dose Evaluation portion of the protocol has
      been removed.

      Participation in the study will cease 6 months after the third dose of BNT162b2.
    

Intervention name(s): Biological/Vaccine: BNT162b2 10mcg; BNT162b2 20mcg; BNT162b2 30mcg; Placebo; Biological/Vaccine: BNT162b2 3mcg
Intervention type(s): Biological; Biological; Biological; Other; Biological
Intervention description(s): BNT162b2 Low/Mid-Dose (10mcg) level; BNT162b2 Mid-Dose (20mcg) level; BNT162b2 High-Dose (30mcg) level; Intramuscular injection; BNT162b2 Low-Dose (3mcg) level
Intervention MeSH terms: Vaccines
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: COVID-19; Coronavirus Vaccine; SARS-CoV-2; RNA Vaccine; mRNA Vaccine