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A Phase 1/2/3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate Against COVID-19 in Healthy Children and Young Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04816643
Recruitment Status : Active, not recruiting
First Posted : March 25, 2021
Last Update Posted : November 23, 2022
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
BioNTech SE

Tracking Information
First Submitted Date  ICMJE March 19, 2021
First Posted Date  ICMJE March 25, 2021
Last Update Posted Date November 23, 2022
Actual Study Start Date  ICMJE March 24, 2021
Estimated Primary Completion Date May 24, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2022)
  • Percentage of participants in Phase 1 reporting local reactions [ Time Frame: for 7 days after Dose 1 and Dose 2 ]
    Pain or tenderness at the injection site, redness and swelling as reported on electronic diaries.
  • Percentage of participants in Phase 1 reporting systemic events [ Time Frame: for 7 days after Dose 1 and Dose 2 ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened join pain, decreased appetite drowsiness, and irritability as reported on electronic diaries
  • Percentage of participants in Phase 1 reporting adverse events [ Time Frame: from Dose 1 through 1 month after the last dose ]
    As elicited by investigational site staff
  • Percentage of participants in Phase 1 reporting serious adverse events [ Time Frame: from Dose 1 through 6 months after the last dose ]
    As elicited by investigational site staff
  • Percentage of participants in Phase 2/3 reporting local reaction [ Time Frame: for 7 days after Dose 1 and Dose 2 ]
    Pain or tenderness at the injection site, redness and swelling as reported on electronic diaries.
  • Percentage of participants in Phase 2/3 reporting systemic events [ Time Frame: for 7 days after Dose 1 and Dose 2 ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain, decreased appetite, drowsiness, and irritability as reported on electronic diaries
  • Percentage of participants in Phase 2/3 reporting adverse events [ Time Frame: from Dose 1 through 1 month after the last dose ]
    As elicited by investigational site staff
  • Percentage of participants in Phase 2/3 reporting serious adverse events [ Time Frame: from Dose 1 through 6 months after the last dose ]
    As elicited by investigational site staff
  • Ph 2/3 selected-dose (2-dose series), immunobridging of SARS-CoV-2 serum neutralizing titers after 2 doses in participants ≥5 to <12 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in participants 16 to 25 years in the C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • Ph 2/3 selected-dose (2-dose series), immunobridging of SARS-CoV-2 serum neutralizing titers after 2 doses in participants ≥2 to <5 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in participants 16 to 25 years in the C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • Ph 2/3 selected-dose (2-dose series), immunobridging of SARS-CoV-2 serum neutralizing titers after 2 doses in participants ≥6 months to <2 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in participants 16 to 25 in C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • In Phase 2/3 selected-dose (2-dose series), the difference in percentages of participants with seroresponse in participants ≥5 to <12 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • In Phase 2/3 selected-dose (2-dose series), the difference in percentages of participants with seroresponse in participants ≥2 to <5 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • In Phase 2/3 selected-dose (2-dose series), the difference in percentages of participants with seroresponse in participants ≥6 months to <2 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • Ph 2/3 selected-dose (3-dose series), immunobridging of SARS-CoV-2 serum neutralizing titers after 3 doses in participants ≥2 to <5 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in C4591001 participants 16 to 25 years after 2 doses [ Time Frame: 1 month after the third dose ]
    As measured at the central laboratory
  • Ph 2/3 selected-dose (3-dose), immunobridging SARS-CoV-2 serum neutralizing titers after 3 doses in participants ≥6 months to <2 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in C4591001 participants 16 to 25 in study after 2 doses [ Time Frame: 1 month after the third dose ]
    As measured at the central laboratory
  • In Phase 2/3 selected-dose (3-dose series), the difference in percentages of participants with seroresponse in participants ≥2 to <5 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 study [ Time Frame: 1 month after the third dose ]
    As measured at the central laboratory
  • In Phase 2/3 selected-dose (3-dose series), the difference in percentages of participants with seroresponse in participants ≥6 months to <2 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 [ Time Frame: 1 month after the third dose ]
    As measured at the central laboratory
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2021)
  • Percentage of participants in Phase 1 reporting local reaction in each dose level in each age group [ Time Frame: for 7 days after Dose 1 and Dose 2 ]
    For participants in ≥5 to <12 years and ≥2 to <5 years of age: Pain at the injection site, redness and swelling as reported on electronic diaries. For participants in ≥6 months to <2 years of age: Tenderness at the injection site, redness, and swelling as reported on electronic diaries
  • Percentage of participants in Phase 1 reporting systemic events in each dose level in each age group [ Time Frame: for 7 days after Dose 1 and Dose 2 ]
    For participants ≥5 to <12 years and ≥2 to <5 years of age Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened join pain as reported on electronic diaries For Participants ≥6 months to <2 years of age Fever, decreased appetite drowsiness, and irritability as reported on electronic diaries
  • Percentage of participants in Phase 1 reporting adverse events in each dose level in each age group [ Time Frame: from Dose 1 through 1 month after the last dose ]
    As elicited by investigational site staff
  • Percentage of participants in Phase 1 reporting serious adverse events in each dose level in each age group [ Time Frame: from Dose 1 through 6 months after the last dose ]
    As elicited by investigational site staff
  • Percentage of participants in Phase 2/3 reporting local reaction in each dose level in each age group [ Time Frame: for 7 days after Dose 1 and Dose 2 ]
    For participants in ≥5 to <12 years and ≥2 to <5 years of age: Pain at the injection site, redness and swelling as reported on electronic diaries. For participants in ≥6 months to <2 years of age: Tenderness at the injection site, redness, and swelling as reported on electronic diaries
  • Percentage of participants in Phase 2/3 reporting systemic events in each dose level in each age group [ Time Frame: for 7 days after Dose 1 and Dose 2 ]
    For participants in ≥5 to <12 years and ≥2 to <5 years of age: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as reported on electronic diaries. For participants in ≥6 months to <2 years of age: Fever, decreased appetite, drowsiness, and irritability as reported on electronic diaries
  • Percentage of participants in Phase 2/3 reporting adverse events in each dose level in each age group [ Time Frame: from Dose 1 through 1 month after the last dose ]
    As elicited by investigational site staff
  • Percentage of participants in Phase 2/3 reporting serious adverse events in each dose level in each age group [ Time Frame: from Dose 1 through 6 months after the last dose ]
    As elicited by investigational site staff
  • In Phase 2/3 participants, Geometric Mean Ratio of SARS-CoV-2 neutralizing titers in participants in each age group at selected dose level to those 16 to 25 years of age in study C4591001 [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2022)
  • In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs [ Time Frame: At each time point ]
    As measured at the central laboratory
  • In evaluable Phase 2/3 participants at selected dose level in each age group, Geometric Mean Titers of SARS-CoV-2 neutralizing titers with no serological or virological evidence of past SARS-CoV-2 infection [ Time Frame: At baseline (before Dose 1) and 1, 6, 12 (for the original BNT162b2 group only), and 24 (for the original BNT162b2 group only) months after Dose 2 ]
    As measured at the central laboratory
  • In evaluable Phase 2/3 participants at the dose level selected in each age group, Geometric Mean Fold Ratio in SARS-CoV-2 serum neutralizing titer from before vaccination to each subsequent time point [ Time Frame: From before Dose 1 to each subsequent time point after Dose 2 ]
    As measured at the central laboratory
  • In the evaluable Phase 2/3 selected-dose participants, Ratio of incidence of asymptomatic SARS-CoV-2 infection based on N-binding antibody seroconversion for the active vaccine group to the placebo group without evidence of past SARS-CoV-2 infection [ Time Frame: Through 6 months after the second dose ]
    As measured at the central laboratory
  • Ph 2/3 LDE participants, immunobridging of SARS-CoV-2 serum neutralizing titers after 2 doses in participants 12 to <16 years of age to the geometric mean of SARS-CoV-2 serum neutralizing titers in participants 16 to 25 years of age in the C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • Ph 2/3 LDE participants, immunobridging of SARS-CoV-2 serum neutralizing titers in participants 16 to <18 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in participants 16 to 55 years from Phase 2/3 of the C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • In Phase 2/3 lower-dose evaluation participants, the difference in percentages of participants with seroresponse in participants 12 to <16 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • In lower-dose evaluation participants, the difference in percentages of participants with seroresponse in participants 16 to <18 years of age and participants 16 to 55 years of age from C4591001 study [ Time Frame: 1 month after the second dose ]
    As measured at the central laboratory
  • Ratio of confirmed COVID-19 illness, Phase 2/3 selected-dose participants ≥5 to <12 years of age with successful immunobridging, without evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group [ Time Frame: From 7 days after the second dose to prior to third dose ]
    Per 1000 person-years of follow-up
  • Ratio of confirmed COVID-19 illness, Phase 2/3 selected-dose participants ≥5 to <12 years of age with successful immunobridging, with and without evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group [ Time Frame: From 7 days after the second dose to prior to third dose ]
    Per 1000 person-years of follow-up
  • Ratio of confirmed COVID-19 illness, Phase 2/3 selected-dose participants ≥6 months to <5 years of age (3-dose series), evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group [ Time Frame: From 7 days after the third dose ]
    1000 person-years of follow-up
  • Ratio of confirmed COVID-19 illness, Phase 2/3 selected-dose participants ≥6 months to <5 years of age (3-dose series), with and without evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group [ Time Frame: From 7 days after the third dose ]
    1000 person-years of follow-up
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2021)
  • In Phase 1 participants in each age group at each dose level, Geometric Mean Titers of SARS-CoV-2 serum neutralizing antibody titers [ Time Frame: Through 7 days after Dose 2 ]
    As measured at the central laboratory
  • In Phase 1 participants in each age group at each dose level, Geometric Mean Fold Ratio in SARS-CoV-2 serum neutralizing antibody titers from before vaccination to each subsequent time point [ Time Frame: Up to 7 days after Dose 2 ]
    As measured at the central laboratory
  • In evaluable Phase 2/3 participants at selected dose level in each age group, Geometric Mean Titers of SARS-CoV-2 neutralizing titers with no serological or virological evidence of past SARS-CoV-2 infection [ Time Frame: At baseline, and at 1, 6, 12(participants who originally received BNT162b2) and 24 months(participants who originally received BNT162b2) after dose 2 ]
    As measured at the central laboratory
  • In evaluable Phase 2/3 participants at selected dose level in each age group, Geometric Mean Fold Ratio in SARS-CoV-2 serum neutralizing titer from before vaccination to each subsequent time point [ Time Frame: from before Dose 1 and at 1, 6, 12(participants who originally received BNT162b2) and 24 months(participants who originally received BNT162b2) after dose 2 ]
    As measured at the central laboratory
  • Ratio of confirmed COVID-19 illness, in all age groups of Phase 2/3 participants without evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group [ Time Frame: from 7 days after the second dose ]
    Per 1001 person-years of follow-up if at least 22 cases are accrued across the age group
  • Ratio of confirmed COVID-19 illness, in all age groups of Phase 2/3 participants with and without evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group [ Time Frame: from 7 days after the second dose ]
    Per 1001 person-years of follow-up if at least 22 cases are accrued across the age group
  • In the evaluable Phase 2/3 participants, Ratio of incidence of asymptomatic SARS-CoV-2 infection based on N-binding antibody seroconversion for the active vaccine group to the placebo group without evidence of past SARS-CoV-2 infection [ Time Frame: Through 6 months after the second dose ]
    As measured at the central laboratory
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1/2/3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate Against COVID-19 in Healthy Children and Young Adults
Official Title  ICMJE A PHASE 1, OPEN-LABEL DOSE-FINDING STUDY TO EVALUATE SAFETY, TOLERABILITY, AND IMMUNOGENICITY AND PHASE 2/3 PLACEBO-CONTROLLED, OBSERVER-BLINDED SAFETY, TOLERABILITY, AND IMMUNOGENICITY STUDY OF A SARS-COV-2 RNA VACCINE CANDIDATE AGAINST COVID-19 IN HEALTHY CHILDREN AND YOUNG ADULTS
Brief Summary

This is a Phase 1/2/3 study in healthy children and young adults.

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 1 Lower-Dose Evaluation

Is the open-label lower-dose evaluation portion of the study that will evaluate the safety, tolerability, and immunogenicity of 10 µg BNT162b2 from 2 schedules in 2 age groups (participants 12 to <16 years and 16 to <18 years of age).

The purpose of the Phase 1 lower-dose evaluation is to evaluate the safety and immunogenicity of BNT162b2 from 2 different dose schedules in each age group: (1) 2 doses separated by approximately 21 days and (2) 2 doses separated by approximately 8 weeks.

Participants will have blood drawn prior to Dose 1, prior to Dose 2, 7 days after Dose 2, and 1 month after Dose 2 to assess immunogenicity to determine the selected BNT162b2 dose schedule for the Phase 2/3 lower-dose evaluation portion of the study. In addition, participants will have blood drawn at 6 and 12 months after Dose 2 to determine the persistence of the immune response.

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 Lower-Dose Evaluation

Is the open-label portion of the study that will evaluate the safety, tolerability, and immunogenicity of the selected dose schedule in each age group from the Phase 1 lower-dose evaluation, with a total of approximately 600 active participants.

Approximately 300 active participants in each age group in this phase will contribute to the immunobridging analysis at 1 month after Dose 2 and the overall analysis of the persistence of immune response at 6 and 12 months after Dose 2.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE SARS-CoV-2 Infection, COVID-19
Intervention  ICMJE
  • Biological: Biological/Vaccine: BNT162b2 10mcg
    BNT162b2 Low/Mid-Dose (10mcg) level
  • Biological: BNT162b2 20mcg
    BNT162b2 Mid-Dose (20mcg) level
  • Biological: BNT162b2 30mcg
    BNT162b2 High-Dose (30mcg) level
  • Other: Placebo
    Intramuscular injection
  • Biological: Biological/Vaccine: BNT162b2 3mcg
    BNT162b2 Low-Dose (3mcg) level
Study Arms  ICMJE
  • Experimental: Low/Mid-Dose, ≥5 to <12 Years
    Low/Mid-Dose (10mcg), 2 doses 21 days apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 10mcg
  • Experimental: Mid-Dose, ≥5 to <12 Years
    Mid-Dose, (20mcg), 2 doses 21 days apart
    Intervention: Biological: BNT162b2 20mcg
  • Experimental: High-Dose, ≥5 to <12 Years
    High-Dose (30mcg), 2 doses 21 days apart
    Intervention: Biological: BNT162b2 30mcg
  • Experimental: Low/Mid-Dose, ≥2 to < 5 Years
    Low/Mid-Dose (10mcg), 2 doses 21 days apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 10mcg
  • Experimental: Mid-Dose, ≥2 to <5 Years
    Mid-Dose, (20mcg), 2 doses 21 days apart
    Intervention: Biological: BNT162b2 20mcg
  • Experimental: High-Dose, ≥2 to <5 Years
    High-Dose, (30mcg), 2 doses 21 days apart
    Intervention: Biological: BNT162b2 30mcg
  • Experimental: Low/Mid-Dose, ≥6 Months to <2 Years
    Low/Mid-Dose, (10mcg), 2 doses 21 days apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 10mcg
  • Experimental: Mid-Dose, ≥6 Months to <2 Years
    Mid-Dose, (20mcg), 2 doses 21 days apart
    Intervention: Biological: BNT162b2 20mcg
  • Experimental: High-Dose, ≥6 Months to <2 Years
    High-Dose, (30mcg), 2 doses 21 days apart
    Intervention: Biological: BNT162b2 30mcg
  • Experimental: Low/Mid-Dose, 16 to <18 Years (21 day schedule)
    Low/Mid-Dose (10mcg), 2 doses 21 days apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 10mcg
  • Placebo Comparator: Placebo, ≥6 Months to <2 Years
    Intervention: Other: Placebo
  • Placebo Comparator: Placebo, ≥2 to <5 Years
    Intervention: Other: Placebo
  • Placebo Comparator: Placebo, ≥5 to <12 Years
    Intervention: Other: Placebo
  • Experimental: Low-Dose, ≥6 Months to <2 Years
    Low-Dose (3mcg), 2 doses 21 doses apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 3mcg
  • Experimental: Low-Dose, ≥2 to <5 Years
    Low-Dose (3mcg), 2 doses 21 days apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 3mcg
  • Experimental: Low/Mid-Dose, 12 to <16 Years (21 day schedule)
    Low/Mid-Dose (10mcg), 2 doses 21 days apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 10mcg
  • Experimental: High-Dose, 12 to <16 Years (Troponin I Testing)
    High-Dose (30mcg), 3 doses
    Intervention: Biological: BNT162b2 30mcg
  • Experimental: Low/Mid-Dose, ≥5 to <12 Years (Troponin I Testing)
    Low/Mid-Dose (10mcg), 3 doses
    Intervention: Biological: Biological/Vaccine: BNT162b2 10mcg
  • Experimental: Placebo, ≥5 to <12 Years (Troponin I Testing)
    Intervention: Other: Placebo
  • Experimental: Low/Mid-Dose, 12 to <16 Years (8 week schedule)
    Low/Mid-Dose (10mcg), 2 doses 8 weeks apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 10mcg
  • Experimental: Low/Mid-Dose, 16 to <18 Years (8 week schedule)
    Low/Mid-Dose (10mcg), 2 doses 8 weeks apart
    Intervention: Biological: Biological/Vaccine: BNT162b2 10mcg
  • Experimental: Low-Dose, ≥6 Months to <2 Years (3-dose regimen)
    Low-Dose (3mcg), 3 doses
    Intervention: Biological: Biological/Vaccine: BNT162b2 3mcg
  • Experimental: Low-Dose, ≥2 to <5 Years (3-dose regimen)
    Low-Dose (3mcg), 3 doses
    Intervention: Biological: Biological/Vaccine: BNT162b2 3mcg
  • Placebo Comparator: Placebo, ≥6 Months to <2 Years (3-dose regimen)
    Intervention: Other: Placebo
  • Placebo Comparator: Placebo, ≥2 to <5 Years (3-dose regimen)
    Intervention: Other: Placebo
Publications * Walter EB, Talaat KR, Sabharwal C, Gurtman A, Lockhart S, Paulsen GC, Barnett ED, Muñoz FM, Maldonado Y, Pahud BA, Domachowske JB, Simões EAF, Sarwar UN, Kitchin N, Cunliffe L, Rojo P, Kuchar E, Rämet M, Munjal I, Perez JL, Frenck RW Jr, Lagkadinou E, Swanson KA, Ma H, Xu X, Koury K, Mather S, Belanger TJ, Cooper D, Türeci Ö, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591007 Clinical Trial Group. Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. N Engl J Med. 2022 Jan 6;386(1):35-46. doi: 10.1056/NEJMoa2116298. Epub 2021 Nov 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 22, 2022)
11111
Original Estimated Enrollment  ICMJE
 (submitted: March 24, 2021)
4644
Estimated Study Completion Date  ICMJE May 24, 2024
Estimated Primary Completion Date May 24, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Male or female participants ≥6 months to <12 years of age, at the time of randomization, at Visit 1 for the dose-finding/selected-dose evaluation and for participants ≥12 to <18 years of age, at the time of randomization, at Visit 1 for the lower-dose evaluation. For the obtaining-serum-samples-for-potential-troponin I-testing portion of the study: Male or female participants between ≥5 and <16 years of age.
  2. Participants' parent(s)/legal guardian(s) and participants, as age appropriate, who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
  3. Healthy participants who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study.

    Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in the therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included.

  4. Participants are expected to be available for the duration of the study and whose parent(s)/legal guardian can be contacted by telephone during study participation.
  5. Negative urine pregnancy test for female participants who are biologically capable of having children.
  6. Female participant of childbearing potential or male participant able to father children who is willing to use a highly effective method of contraception as outlined in this protocol for at least 28 days after the last dose of study intervention if at risk of pregnancy with her/his partner; or female participant not of childbearing potential or male participant not able to father children.
  7. The participant or participant's parent(s)/legal guardian is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Depending on the age of the participant and according to local requirements, participants will also be asked to provide assent as appropriate (verbal or written).

Exclusion Criteria

  1. Phase 1 only: Past clinical (based on COVID-19 symptoms/signs alone, if a SARS CoV 2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID 19.
  2. Phase 1 only: Known infection with HIV, HCV, or HBV.
  3. Receipt of medications intended to prevent COVID-19.
  4. Previous or current diagnosis of MIS-C.
  5. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Note: This includes both conditions that may increase the risk associated with study intervention administration or a condition that may interfere with the interpretation of study results
  6. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
  7. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  8. Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus. Note: Stable type 1 diabetes and hypothyroidism are permitted.
  9. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  10. Female who is pregnant or breastfeeding.
  11. Previous vaccination with any coronavirus vaccine.
  12. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
  13. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.
  14. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
  15. Previous participation in other studies involving study intervention containing LNPs.
  16. Participants who are direct descendants (child or grandchild) of investigational site staff members or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Finland,   Mexico,   Poland,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04816643
Other Study ID Numbers  ICMJE C4591007
2020-005442-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party BioNTech SE
Original Responsible Party Same as current
Current Study Sponsor  ICMJE BioNTech SE
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account BioNTech SE
Verification Date November 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP