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Trial record 2 of 7 for:    C4591001

To Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of BNT162b2 Boosting Strategies Against COVID-19 in Participants ≥12 Years of Age.

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: NCT04955626
Recruitment Status : Active, not recruiting
First Posted : July 9, 2021
Last Update Posted : October 5, 2022
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
BioNTech SE

Tracking Information
First Submitted Date  ICMJE June 9, 2021
First Posted Date  ICMJE July 9, 2021
Last Update Posted Date October 5, 2022
Actual Study Start Date  ICMJE July 1, 2021
Estimated Primary Completion Date April 12, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2022)
  • SSA - Confirmed COVID-19 incidence in participants without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • SSA - Confirmed COVID-19 incidence in participants with and without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • SSA - Percentage of participants reporting adverse events [ Time Frame: from the booster dose to 1 month after the booster dose ]
    As elicited by investigational site staff
  • SSA - Percentage of participants reporting serious adverse events [ Time Frame: from the booster dose to 6 months after the booster dose ]
    As elicited by investigational site staff
  • SSB - Percentage of participants with elevated troponin I levels [ Time Frame: through 1 month after the second vaccination ]
    Troponin I level
  • SSB - Percentage of participants reporting local reactions [ Time Frame: For 7 days following each vaccination ]
    Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
  • SSB - Percentage of participants reporting systemic events [ Time Frame: For 7 days following each vaccination ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
  • SSB - Percentage of participants reporting adverse events [ Time Frame: within 1 month after each vaccination ]
    As elicited by investigational site staff
  • SSB - Percentage of participants reporting serious adverse events [ Time Frame: within 1 month after each vaccination ]
    As elicited by investigational site staff
  • SSC - Percentage of participants reporting local reactions [ Time Frame: For 7 days following the booster dose ]
    Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
  • SSC - Percentage of participants reporting systemic events [ Time Frame: For 7 days following the booster dose ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
  • SSC - Percentage of participants reporting adverse events [ Time Frame: from the booster dose to 1 month after the booster dose ]
    As elicited by investigational site staff
  • SSC - Percentage of participants reporting serious adverse events [ Time Frame: from the booster dose to 6 months after the booster dose ]
    As elicited by investigational site staff
  • SSC - For each of the 2 age groups (12 through 17, and ≥56 years of age): Demonstrate immunobridging of immune response of D3 of BNT162b2 at 30 µg compared to after D2 in age-matched participants from the C4591001 study [ Time Frame: 1 month after the booster (third) dose, and 1 month after the second dose for participants in the control group ]
    GMR, estimated by the ratio of the GMTs of SARS-CoV-2 neutralizing titers at 1 month after the third dose in participants who received a booster (third) dose of BNT162b2 at 30 µg to those at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study. The difference in the percentage of participants with seroresponse at 1 month after the third dose in participants who received a booster (third) dose of BNT162b2 at 30 µg and at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study
  • SSC - For each of the 4 age groups (12 through 17, 18 through 30, 31 through 55, and ≥56 years of age): Demonstrate immunobridging of immune response of D3 of BNT162b2 at 10 µg compared to after D2 in age-matched participants from the C4591001 study [ Time Frame: 1 month after the booster (third) dose, and 1 month after the second dose for participants in the control group ]
    GMR, estimated by the ratio of the GMTs of SARS-CoV-2 neutralizing titers at 1 month after the third dose in participants who received a booster (third) dose of BNT162b2 at 10 µg to those at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study. The difference in percentage of participants with seroresponse at 1 month after the third dose in participants who received a booster (third) dose of BNT162b2 at 10 µg and at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study
  • SSD - Percentage of participants reporting local reactions [ Time Frame: For 7 days following each vaccination ]
    Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
  • SSD - Percentage of participants reporting systemic events [ Time Frame: For 7 days following each vaccination ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
  • SSD - Percentage of participants reporting adverse events [ Time Frame: from the first study vaccination (received in this study) through 1 month after the last study vaccination ]
    As elicited by investigational site staff
  • SSD - Percentage of participants reporting serious adverse events [ Time Frame: from the first study vaccination (received in this study) through 6 months after the last study vaccination ]
    As elicited by investigational site staff
  • SSD-Superiority with respect to neutralizing titers and noninferiority with respect to seroresponse rate of the anti-Omi immune response after 1 dose of BNT162b2 OMI compared to after 1 dose of BNT162b2 given as D3 in BNT162b2-experienced participants [ Time Frame: 1 month after receipt of 1 dose of study intervention ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of BNT162b2 OMI and at 1 month after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants
  • SSD-Superiority with respect to neutralizing titers and noninferiority with respect to seroresponse of anti-Omi immune response after 2 doses BNT162b2 OMI given as D3+D4 compared to after 1 dose BNT162b2 given as D3 in BNT162b2-experienced participants [ Time Frame: 1 month after receipt of 1 or 2 doses of intervention as appropriate ]
    GMR of the Omicron-neutralizing titers at 1 month after 2 doses of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the third (and fourth) dose in BNT162b2-experienced participants The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 2 doses of BNT162b2 OMI and at 1 month after 1 dose of BNT162b2 given as the third (and fourth) dose in BNT162b2-experienced participants
  • SSD-Superiority with respect to neutralizing titer and noninferiority with respect to seroresponse rate of the anti-Omi immune response after 1 dose BNT162b2 OMI compared to after 1 dose BNT162b2 given as the D4 in BNT162b2-experienced participants [ Time Frame: 1 month after receipt of 1 dose of study intervention ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the fourth dose in BNT162b2-experienced participants The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of BNT162b2 OMI and at 1 month after 1 dose of BNT162b2 given as the fourth dose in BNT162b2-experienced participants
  • SSD-Superiority with respect to neutralizing titer and noninferiority with respect to seroresponse rate of the anti-Omi immune response after 2 doses BNT162b2 OMI compared to after 2 doses BNT162b2 in age-matched participants from the C4591001 study [ Time Frame: 1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate ]
    GMR of the Omicron-neutralizing titers 1 month after the second dose of BNT162b2 OMI to 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after the second dose of BNT162b2 OMI and at 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study
  • SSE - Percentage of participants reporting local reactions [ Time Frame: For 7 days following the study vaccination ]
    Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
  • SSE - Percentage of participants reporting systemic events [ Time Frame: For 7 days following the study vaccination ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
  • SSE - Percentage of participants reporting adverse events [ Time Frame: from the study vaccination through 1 month after the study vaccination ]
    As elicited by investigational site staff
  • SSE - Percentage of participants reporting serious adverse events [ Time Frame: from the study vaccination through 6 months after the study vaccination ]
    As elicited by investigational site staff
  • SSE - Percentage of participants with elevated troponin I levels (18-55 years of age, sentinel cohort only) [ Time Frame: Before and 3 days after study vaccination ]
    Troponin I level
  • SSE - Superiority of neutralizing titer after 1 dose of BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - Noninferiority of anti-Omicron immune response after 1 dose of BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of BNT162b2 OMI 30 µg and at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - Superiority of neutralizing titer after 1 dose of BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - Noninferiority of anti-Omicron immune response after 1 dose of BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of BNT162b2 OMI 60 µg and at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - Superiority of neutralizing titer after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - Noninferiority of anti-Omicron immune response after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg and at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - Superiority of neutralizing titer after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2
  • SSE - Noninferiority of anti-Omicron immune response after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg and at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSF - Percentage of participants reporting local reactions [ Time Frame: For 7 days following the study vaccination ]
    Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
  • SSF - Percentage of participants reporting systemic events [ Time Frame: For 7 days following the study vaccination ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
  • SSF - Percentage of participants reporting adverse events [ Time Frame: from the study vaccination through 1 month after the study vaccination ]
    As elicited by investigational site staff
  • SSF - Percentage of participants reporting serious adverse events [ Time Frame: from the study vaccination through 6 months after the study vaccination ]
    As elicited by investigational site staff
  • SSF - To describe the immune response to BNT162b2 (30 µg or 60 µg), BNT162b2 OMI (30 µg or 60 µg), and a combination of BNT162b2 and BNT162b2 OMI (30 µg or 60 µg) given as a fourth dose in BNT162b2-experienced participants [ Time Frame: At each time point ]
    GMT of Omicron and reference-strain neutralizing titers GMFRs of Omicron and reference-strain neutralizing titers from before the study vaccination to subsequent time points Percentages of participants with seroresponse for Omicron and reference-strain neutralizing titers at each time point
Original Primary Outcome Measures  ICMJE
 (submitted: June 29, 2021)
  • Confirmed COVID-19 incidence in participants without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • Confirmed COVID-19 incidence in participants with and without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • Percentage of participants reporting adverse events [ Time Frame: from the booster dose to 1 month after the booster dose ]
    As elicited by investigational site staff
  • Percentage of participants reporting serious adverse events [ Time Frame: from the booster dose to 6 months after the booster dose ]
    As elicited by investigational site staff
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2022)
  • SSA - Confirmed severe COVID-19 (based on FDA definition) period in participants without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • SSA - Confirmed severe COVID-19 (based on FDA definition) in participants with and without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • SSA - Confirmed severe COVID-19 (based on CDC definition) in participants without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • SSA - Confirmed severe COVID-19 (based on CDC definition) in participants with and without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • SSC - Immune responses induced by a booster (third) dose of BNT162b2 at 10 µg and 30 µg [ Time Frame: Through 1 year after the booster (third) dose ]
    GMTs of SARS-CoV-2 neutralizing titers GMFRs of SARS-CoV-2 neutralizing titers
  • SSD - The "super" superiority of the anti-Omicron immune response after 1 dose of BNT162b2 OMI compared to after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants [ Time Frame: 1 month after receipt of 1 dose of study intervention ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants
  • SSD - The "super" superiority of the anti-Omicron immune response after 2 doses of BNT162b2 OMI given as the third and fourth doses compared to after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants [ Time Frame: 1 month after receipt of 1 or 2 doses of intervention as appropriate ]
    GMR of the Omicron-neutralizing titers at 1 month after 2 doses of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the third (and fourth) dose in BNT162b2-experienced participants
  • SSD - The "super" superiority of the anti-Omicron immune response after 1 dose of BNT162b2 OMI compared to after 1 dose of BNT162b2 given as the fourth dose in BNT162b2-experienced participants [ Time Frame: 1 month after receipt of 1 dose of study intervention ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the fourth dose in BNT162b2-experienced participants
  • SSD - The noninferiority of the anti-Omicron immune response after 2 doses of BNT162b2 OMI compared to the anti-reference-strain immune response after 2 doses of BNT162b2 in age-matched participants randomly selected from the C4591001 study [ Time Frame: 1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate ]
    GMR of the Omicron-neutralizing titers 1 month after the second dose of BNT162b2 OMI to the reference-strain-neutralizing titers 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after the second dose of BNT162b2 OMI and seroresponsea to the reference strain at 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study
  • SSD - The "super" superiority of the anti-Omicron immune response after 2 doses of BNT162b2 OMI compared to after 2 doses of BNT162b2 in age-matched participants randomly selected from the C4591001 study [ Time Frame: 1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate ]
    GMR of the Omicron-neutralizing titers 1 month after the second dose of BNT162b2 OMI to 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study
  • SSE - Noninferiority of anti-reference-strain immune response after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the reference strain-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - Noninferiority of anti-reference strain immune response after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the reference strain-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - The "super" superiority of anti-Omicron immune responses after 1 dose of BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - The "super" superiority of anti-Omicron immune responses after 1 dose of BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - The "super" superiority of anti-Omicron immune responses after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
  • SSE - The "super" superiority of anti-Omicron immune responses after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [ Time Frame: 1 month after receipt of 1 dose of study intervention given as a fourth dose ]
    GMR of the Omicron-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
Original Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2021)
  • Confirmed severe COVID-19 (based on FDA definition) period in participants without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • Confirmed severe COVID-19 (based on FDA definition) in participants with and without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • Confirmed severe COVID-19 (based on CDC definition) in participants without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • Confirmed severe COVID-19 (based on CDC definition) in participants with and without evidence of past SARS-CoV-2 infection [ Time Frame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of blinded follow-up
  • Incidence of asymptomatic SARS-CoV-2 infection based on N-binding antibody in participants without evidence of past SARS-CoV-2 infection [ Time Frame: From the booster dose through the blinded follow-up period, which may be from 2 to 12 months ]
    per 1000 person-years of follow-up
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE To Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of BNT162b2 Boosting Strategies Against COVID-19 in Participants ≥12 Years of Age.
Official Title  ICMJE A PHASE 3 MASTER PROTOCOL TO EVALUATE ADDITIONAL DOSE(S) OF BNT162B2 IN HEALTHY INDIVIDUALS PREVIOUSLY VACCINATED WITH BNT162B2
Brief Summary

Substudy A: The study will evaluate the safety, tolerability, and efficacy of a booster dose of BNT162b2 when administered to participants having previously received 2 doses of BNT162b2 at least 6 months prior to randomization.

The study is designed to describe vaccine efficacy of a booster dose of BNT162b2 over time against COVID-19

  • At a dose of 30µg (as studied in the Phase 2/3 study C4591001)
  • In healthy adults 16 years of age and older
  • The duration of the study for each participant will be up to approximately 12 months.
  • The study will be conducted in the United States, Brazil and South Africa

Substudy B: The study will assess the safety and tolerability of a single dose of BNT162b2 as compared to placebo control, through the potential analysis of serum troponin levels, in participants ≥12 and ≤30 years of age who have received 2 or 3 prior doses of BNT162b2 (30-µg doses) with their last dose at least 4 months (120 days) prior to randomization.

  • Blood samples will be collected for troponin testing
  • The duration of the study for each participant will be up to approximately 2 months.
  • The study will be conducted in the United States, Germany, Poland and South Africa

Substudy C: The study will assess the safety, tolerability, and immunogenicity of a booster (third) dose of BNT162b2 at doses of 10 µg or 30 µg in participants who have completed a 2-dose primary series of BNT162b2 (30 µg doses) at least 5 months (150 days) prior to randomization.

  • In healthy adults 12 years of age and older
  • The duration of the study for each participant will be up to approximately 12 months.
  • The study will be conducted in the United States, Germany and South Africa

Substudy D: The study will assess the safety, tolerability, and immunogenicity of a 2-dose primary series of BNT162b2 OMI, and as a booster (third, fourth or fifth) dose

  • Participants in Cohort 1 will have completed a 2-dose primary series of BNT162b2 (30-µg doses), with their last dose 90 to 240 days prior to enrolment
  • Participants in Cohort 2 will be enrolled from Study C4591001 and C4591031 Substudy A and will have completed a 2-dose primary series and received a single booster (third) dose of BNT162b2, with their last dose 90 to 180 days prior to randomization
  • Participants in Cohort 3 who are COVID-19 vaccine-naïve and have not experienced COVID-19 will be enrolled to receive 2 doses (primary series) of BNT162b2 OMI, 3 weeks apart, with a dose of BNT162b2 approximately 5 months (150 days) later. If participants do not consent to receive BNT162b2 as a third dose, they will not receive a third dose. No participants should receive BNT162b2 OMI as a third dose.

    • In healthy adults 18 to 55 years of age
    • The duration of the study for each participant will be up to approximately 12 months.
    • The study will be conducted in the United States and South Africa

Substudy E: This study will assess the safety, tolerability, and immunogenicity of high-dose BNT162b2 (60 µg), high-dose BNT162b2 OMI (60 µg), and a high-dose combination of BNT162b2 and BNT162b2 OMI at 60 µg (30 µg each), given as a single dose

  • In healthy adults 18 years of age and older who have received 3 prior doses of BNT162b2 (30 µg) with the most recent dose being 5 to 12 months (150 to 360 days) prior to randomization
  • The duration of the study for each participant will be approximately 6 months.
  • The study will be conducted in the United States

Substudy F: This study will assess the safety, tolerability, and immunogenicity of high-dose BNT162b2 (60 µg), high-dose BNT162b2 OMI (60 µg), and a high-dose combination of BNT162b2 and BNT162b2 OMI at 60 µg (30 µg each), given as a single dose.

  • In healthy adults 60 years of age and older who have received 3 prior doses of BNT162b2 (30 µg) with the most recent dose being ≥4 months prior to randomization
  • The duration of the study for each participant will be approximately 6 months.
  • The study will be conducted in Israel
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • SARS-CoV-2 Infection
  • COVID-19
Intervention  ICMJE
  • Biological: BNT162b2
    Intramuscular Injection
  • Other: Placebo
    Intramuscular Injection
  • Biological: BNT162b2 OMI
    Intramuscular Injection
  • Biological: Combination BNT162b2 and BNT162b2 OMI

    30-µg (15-µg each) or 60-µg (30-µg each)

    Site prepared dosing suspension from 1 vial each of diluted BNT162b2 and BNT162b2 OMI

    Intramuscular Injection

  • Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI

    30-µg (15-µg each) or 60-µg (30-µg each)

    Preformulated bivalent mixture (no dilution required) presented in a single vial

    Intramuscular Injection

Study Arms  ICMJE
  • Experimental: 10 µg dose
    1 dose
    Intervention: Biological: BNT162b2
  • Placebo Comparator: Placebo
    1 dose
    Intervention: Other: Placebo
  • Experimental: 30 µg dose
    1 dose
    Interventions:
    • Biological: BNT162b2
    • Biological: BNT162b2 OMI
    • Biological: Combination BNT162b2 and BNT162b2 OMI
    • Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI
  • Experimental: 60 µg dose
    1 dose
    Interventions:
    • Biological: BNT162b2
    • Biological: BNT162b2 OMI
    • Biological: Combination BNT162b2 and BNT162b2 OMI
    • Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI
Publications * Moreira ED Jr, Kitchin N, Xu X, Dychter SS, Lockhart S, Gurtman A, Perez JL, Zerbini C, Dever ME, Jennings TW, Brandon DM, Cannon KD, Koren MJ, Denham DS, Berhe M, Fitz-Patrick D, Hammitt LL, Klein NP, Nell H, Keep G, Wang X, Koury K, Swanson KA, Cooper D, Lu C, Türeci Ö, Lagkadinou E, Tresnan DB, Dormitzer PR, Şahin U, Gruber WC, Jansen KU; C4591031 Clinical Trial Group. Safety and Efficacy of a Third Dose of BNT162b2 Covid-19 Vaccine. N Engl J Med. 2022 May 19;386(20):1910-1921. doi: 10.1056/NEJMoa2200674. Epub 2022 Mar 23.

*   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: October 4, 2022)
16373
Original Estimated Enrollment  ICMJE
 (submitted: June 29, 2021)
10000
Estimated Study Completion Date  ICMJE April 12, 2023
Estimated Primary Completion Date April 12, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Substudy A

Inclusion Criteria:

  • Male or female participants ≥16 years of age at Visit 1 (Day 1) who participated in C4591001.
  • Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
  • Capable of giving signed informed consent.
  • Participants who have received 2 prior doses of 30 µg BNT162b2 19-42 days apart, with the second dose being at least 175 days before Visit 1 (Day 1).

Exclusion Criteria:

  • 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.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
  • Previous 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.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Women who are pregnant or breastfeeding.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  • 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.
  • Prior receipt of any COVID-19 vaccine other than BNT162b2.
  • Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
  • Receipt of medications intended to prevent COVID-19.
  • Prior receipt of more than 2 doses of BNT162b2 30 µg.
  • Participation in other studies involving study intervention within 28 days prior to study entry, other than C4591001, and/or within 28 days of confirmed receipt of BNT162b2 within the study.

Substudy B

Inclusion Criteria:

  • Male or female participants 12 to 30 years of age, inclusive, who have received 2 prior doses of 30 µg BNT162b2 19 to 60 days apart, with the second dose being at least at least 4 months (120 days) before Visit 1 (Day 1)
  • Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
  • Capable of giving signed informed consent.

Exclusion Criteria:

  • Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
  • Previous 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.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Women who are pregnant or breastfeeding.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  • 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.
  • Prior receipt of any COVID-19 vaccine other than BNT162b2.
  • Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
  • Receipt of medications intended to prevent COVID-19.
  • Prior receipt of more than 3 doses of BNT162b2 30 µg.
  • Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.

Substudy C

Inclusion Criteria:

  • Male or female participants ≥12 years of age, inclusive, who have received 2 prior doses of 30 µg BNT162b2 19 to 60 days apart, with the second dose being at least 150 days before Visit 301 (Day 1)
  • Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
  • Capable of giving signed informed consent.

Exclusion Criteria:

  • Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
  • Previous 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.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Women who are pregnant or breastfeeding.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  • 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.
  • Prior receipt of any COVID-19 vaccine other than BNT162b2.
  • Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
  • Receipt of medications intended to prevent COVID-19.
  • Prior receipt of more than 2 doses of BNT162b2 30 µg.
  • Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.

Substudy D

Inclusion Criteria:

  • Male or female participants 18 to 55 years of age inclusive
  • Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
  • Cohort 2: Participants who provided a serum sample at Visit 3 in Study C4591001, with Visit 3 occurring within the protocol-specified window.
  • Capable of giving signed informed consent
  • Cohort 1: Participants who have received 2 prior doses of 30 µg BNT162b2, with the second dose being 90 to 240 days before Visit 401 (Day 1) or Cohort 2: Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being 90 to 180 days before Visit 401 (Day 1).

Exclusion Criteria:

  • 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.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
  • Previous 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.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Women who are pregnant or breastfeeding.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  • 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.
  • Cohorts 1 and 2: prior receipt of any COVID-19 vaccine other than BNT162b2.
  • Cohort 3 only: prior receipt of any COVID-19 vaccine.
  • Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
  • Receipt of medications intended to prevent COVID 19.
  • Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.

Substudy E

Inclusion Criteria:

  • Groups 1-6: Male or female participants >55 years of age
  • Groups 7-9: Male or female participants 18 to 55 years of age
  • Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
  • Capable of giving signed informed consent.
  • Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being 5 to 12 months (150 to 360 days) before Visit 601 (Day 1).
  • Groups 7 to 9 (sentinel participants): Screening troponin levels must be within normal range prior to randomization.

Exclusion Criteria:

  • 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.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
  • Previous 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.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Women who are pregnant or breastfeeding.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  • 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.
  • Prior receipt of any COVID-19 vaccine other than BNT162b2.
  • Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
  • Receipt of medications intended to prevent COVID-19.
  • Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.

Substudy F

Inclusion Criteria:

  • Male or female participants ≥60 years of age
  • Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
  • Capable of giving signed informed consent.
  • Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being ≥4 months before Visit 701 (Day 1).

Exclusion Criteria:

  • 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.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
  • Previous 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.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Women who are pregnant or breastfeeding.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  • 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.
  • Prior receipt of any COVID-19 vaccine other than BNT162b2.
  • Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
  • Receipt of medications intended to prevent COVID-19.
  • Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Canada,   Germany,   Israel,   South Africa,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04955626
Other Study ID Numbers  ICMJE C4591031
2021-005197-25 ( 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 October 2022

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