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To Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of a Booster Dose of BNT162b2 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 : December 22, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
BioNTech SE

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 completed a 2-dose primary series of BNT162b2 (30-µg doses) at least 6 months (≥12 months for those 12 through 17 years of age) 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 6 months prior to randomization (≥12 months for those 12-17 years of age).

  • 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, Poland and South Africa

Condition or disease Intervention/treatment Phase
SARS-CoV-2 Infection COVID-19 Biological: BNT162b2 Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A PHASE 3 MASTER PROTOCOL TO EVALUATE ADDITIONAL DOSE(S) OF BNT162B2 IN HEALTHY INDIVIDUALS PREVIOUSLY VACCINATED WITH BNT162B2
Actual Study Start Date : July 1, 2021
Estimated Primary Completion Date : September 20, 2023
Estimated Study Completion Date : September 20, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 10 µg dose
1 dose
Biological: BNT162b2
Intramuscular Injection

Placebo Comparator: Placebo
1 dose
Other: Placebo
Intramuscular Injection

Experimental: 30 µg dose
1 dose
Biological: BNT162b2
Intramuscular Injection




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. SSB - Percentage of participants with elevated troponin I levels [ Time Frame: through 1 month after the second vaccination ]
    Troponin I level

  6. 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.

  7. 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.

  8. SSB - Percentage of participants reporting adverse events [ Time Frame: within 1 month after each vaccination ]
    As elicited by investigational site staff

  9. SSB - Percentage of participants reporting serious adverse events [ Time Frame: within 1 month after each vaccination ]
    As elicited by investigational site staff

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. SSC - Demonstrate immunobridging of immune response of a booster (third) dose of BNT162b2 at 30 µg compared to after the second dose in the same set of participants 12 through 17 years of age without evidence of SARS-CoV-2 infection [ Time Frame: 1 month after the booster (third) dose ]

    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 the same set of participants.

    The difference in the percentage of participants with seroresponse at 1 month after a booster (third) dose of BNT162b2 at 30 µg and at 1 month after the second dose in the same set of participants


  15. SSC - Demonstrate immunobridging of immune response of a booster (third) dose of BNT162b2 at 10 µg compared to after the second dose in the same set of participants 12 through 17 years of age without evidence of SARS-CoV-2 infection [ Time Frame: 1 month after the booster (third) dose ]
    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 the same set of participants The difference in the percentage of participants with seroresponse in participants at 1 month after a booster (third) dose of BNT162b2 at 10 µg and at 1 month after the second dose in the same set of participants

  16. SSC - Demonstrate immunobridging of immune response of a third dose of BNT162b2 at 10 µg in participants 18 to 30 years of age compared to after the second dose in age-matched participants from the C4591001 study, without evidence of SARS-CoV-2 infection [ 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.

    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


  17. SSC - Demonstrate immunobridging of immune response of a third dose of BNT162b2 at 10 µg in participants 31 to 55 years of age compared to after the second dose in age-matched participants from the C4591001 study, without evidence of SARS-CoV-2 infection [ 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.

    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 10 µg and at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study


  18. SSC - Demonstrate immunobridging of immune response of a third dose of BNT162b2 at 30 µg in participants ≥56 years of age compared to after the second dose in age-matched participants from the C4591001 study, without evidence of SARS-CoV-2 infection [ 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 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

  19. SSC - Demonstrate immunobridging of immune response of a third dose of BNT162b2 at 10 µg in participants ≥56 years of age compared to after the second dose in age-matched participants from the C4591001 study, without evidence of SARS-CoV-2 infection [ 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 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 10 µg and at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. SSA - 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

  6. SSC - SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs, for each vaccine and age group [ Time Frame: Through 1 year after the booster (third) dose ]
    As measured at the central laboratory

  7. SSC - GMFRs in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point, for each vaccine and age group [ Time Frame: Through 1 year after the booster (third) dose ]
    As measured at the central laboratory



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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:

    • 18 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 175 days before Visit 1 (Day 1) or
    • 12 to 17 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 365 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/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 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:

    • ≥18 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 175 days before Visit 301 (Day 1) or
    • 12 to 17 years of age, inclusive, who have received 2 prior doses of 30 µg BNT162b2 19 to 60 days apart in Study C4591001, with the second dose being at least 365 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/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.
  • Bleedin doses of 30 µg BNT162b2 19-42 days apart, with the second dose being at least 175 days before Visit 1 (Day 1). g 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..

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04955626


Locations
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Sponsors and Collaborators
BioNTech SE
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: BioNTech SE
ClinicalTrials.gov Identifier: NCT04955626    
Other Study ID Numbers: C4591031
2021-005197-25 ( EudraCT Number )
First Posted: July 9, 2021    Key Record Dates
Last Update Posted: December 22, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioNTech SE:
COVID-19
Coronavirus
Vaccine
SARS-CoV-2
RNA Vaccine
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases