Clinical trial NCT04955626: To Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of BNT162b2 Boosting Strategies Against COVID-19 in Participants ≥12 Years of Age.
Official title: A PHASE 3 MASTER PROTOCOL TO EVALUATE ADDITIONAL DOSE(S) OF BNT162B2 IN HEALTHY INDIVIDUALS PREVIOUSLY VACCINATED WITH BNT162B2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS-CoV-2 Infection
COVID-19
Keywords: COVID-19
Coronavirus
Vaccine
SARS-CoV-2
RNA Vaccine
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2021-07-09
Enrollment: 16385
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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


Eligibility 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 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.

Primary outcomes:
measure: SSA - Confirmed COVID-19 incidence in participants without evidence of past SARS-CoV-2 infection
timeFrame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months
measure: SSA - Confirmed COVID-19 incidence in participants with and without evidence of past SARS-CoV-2 infection
timeFrame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months
measure: SSA - Percentage of participants reporting adverse events
timeFrame: from the booster dose to 1 month after the booster dose
measure: SSA - Percentage of participants reporting serious adverse events
timeFrame: from the booster dose to 6 months after the booster dose
measure: SSB - Percentage of participants with elevated troponin I levels
timeFrame: through 1 month after the second vaccination
measure: SSB - Percentage of participants reporting local reactions
timeFrame: For 7 days following each vaccination
measure: SSB - Percentage of participants reporting systemic events
timeFrame: For 7 days following each vaccination
measure: SSB - Percentage of participants reporting adverse events
timeFrame: within 1 month after each vaccination
measure: SSB - Percentage of participants reporting serious adverse events
timeFrame: within 1 month after each vaccination
measure: SSC - Percentage of participants reporting local reactions
timeFrame: For 7 days following the booster dose
measure: SSC - Percentage of participants reporting systemic events
timeFrame: For 7 days following the booster dose
measure: SSC - Percentage of participants reporting adverse events
timeFrame: from the booster dose to 1 month after the booster dose
measure: SSC - Percentage of participants reporting serious adverse events
timeFrame: from the booster dose to 6 months after the booster dose
measure: SSC - the immune response to BNT162b2 10 µg and 30 µg given as the third dose in participants 12 through 17 years of age and a third dose of BNT162b2 30 µg in a randomly selected subset of participants 18 through 55 years of age from study C4591001
timeFrame: At baseline (before the third dose), 1 month and 6 months after the third dose
measure: SSD - Percentage of participants reporting local reactions
timeFrame: For 7 days following each vaccination
measure: SSD - Percentage of participants reporting systemic events
timeFrame: For 7 days following each vaccination
measure: SSD - Percentage of participants reporting adverse events
timeFrame: from the first study vaccination (received in this study) through 1 month after the last study vaccination
measure: SSD - Percentage of participants reporting serious adverse events
timeFrame: from the first study vaccination (received in this study) through 6 months after the last study vaccination
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention
measure: 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
timeFrame: 1 month after receipt of 1 or 2 doses of intervention as appropriate
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention
measure: 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 participants from the C4591001 study
timeFrame: 1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate
measure: SSE - Percentage of participants reporting local reactions
timeFrame: For 7 days following the study vaccination
measure: SSE - Percentage of participants reporting systemic events
timeFrame: For 7 days following the study vaccination
measure: SSE - Percentage of participants reporting adverse events
timeFrame: from the study vaccination through 1 month after the study vaccination
measure: SSE - Percentage of participants reporting serious adverse events
timeFrame: from the study vaccination through 6 months after the study vaccination
measure: SSE - Percentage of participants with elevated troponin I levels (18-55 years of age, sentinel cohort only)
timeFrame: Before and 3 days after study vaccination
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: SSF - Percentage of participants reporting local reactions
timeFrame: For 7 days following the study vaccination
measure: SSF - Percentage of participants reporting systemic events
timeFrame: For 7 days following the study vaccination
measure: SSF - Percentage of participants reporting adverse events
timeFrame: from the study vaccination through 1 month after the study vaccination
measure: SSF - Percentage of participants reporting serious adverse events
timeFrame: from the study vaccination through 6 months after the study vaccination
measure: 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
timeFrame: At each time point
Secondary outcomes:
measure: SSA - Confirmed severe COVID-19 (based on FDA definition) period in participants without evidence of past SARS-CoV-2 infection
timeFrame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months
measure: SSA - Confirmed severe COVID-19 (based on FDA definition) in participants with and without evidence of past SARS-CoV-2 infection
timeFrame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months
measure: SSA - Confirmed severe COVID-19 (based on CDC definition) in participants without evidence of past SARS-CoV-2 infection
timeFrame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months
measure: SSA - Confirmed severe COVID-19 (based on CDC definition) in participants with and without evidence of past SARS-CoV-2 infection
timeFrame: from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months
measure: SSC - Immune responses to BNT162b2 10 µg and 30 µg given as the third dose in participants 12 through 17 years of age
timeFrame: At baseline (before the third dose) and 7 days after the third dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention
measure: 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
timeFrame: 1 month after receipt of 1 or 2 doses of intervention as appropriate
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention
measure: 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 participants selected from the C4591001 study
timeFrame: 1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate
measure: SSD - The "super" superiority of the anti-Omicron immune response after 2 doses of BNT162b2 OMI compared to after 2 doses of BNT162b2 in participants selected from the C4591001 study
timeFrame: 1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
measure: 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
timeFrame: 1 month after receipt of 1 dose of study intervention given as a fourth dose
Other outcomes:
Locations:
city: Athens
country: United States
facility: North Alabama Research Center
state: Alabama
city: Birmingham
country: United States
facility: Accel Research Sites - Birmingham Clinical Research Unit
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center
state: Alabama
city: Mobile
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Alabama
city: Chinle
country: United States
facility: Johns Hopkins Center for American Indian Health
state: Arizona
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Phoenix
country: United States
facility: The Pain Center of Arizona
state: Arizona
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Tempe
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Arizona
city: Whiteriver
country: United States
facility: Johns Hopkins Center for American Indian Health
state: Arizona
city: Whiteriver
country: United States
facility: Whiteriver Indian Hospital- Garrett Building
state: Arizona
city: Whiteriver
country: United States
facility: Whiteriver Indian Hospital
state: Arizona
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research, LLC
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Kaiser Permenente Medical Center Infectious Disease
state: California
city: Los Angeles
country: United States
facility: Velocity Clinical Research, Westlake
state: California
city: North Hollywood
country: United States
facility: Velocity Clinical Research, North Hollywood
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland
state: California
city: Redding
country: United States
facility: Paradigm Clinical Research Centers, Inc
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Santa Clara
state: California
city: Valley Village
country: United States
facility: Bayview Research Group, LLC
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Aurora
country: United States
facility: Lynn Institute of Denver
state: Colorado
city: Milford
country: United States
facility: Clinical Research Consulting
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale Center for Clinical Investigation
state: Connecticut
city: Coral Gables
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood )
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
state: Florida
city: Miami
country: United States
facility: Acevedo Clinical Research Associates
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research, LLC
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Meridian
country: United States
facility: Solaris Clinical Research
state: Idaho
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Sioux City
country: United States
facility: Velocity Clinical Research, Sioux City
state: Iowa
city: Newton
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Wichita
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric/ Adult Research
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research (MICHMER)
state: Michigan
city: Gulfport
country: United States
facility: MedPharmics, LLC
state: Mississippi
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital d/b/a Bozeman Health Clinical Research
state: Montana
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital
state: Montana
city: Fremont
country: United States
facility: Methodist Physicians Clinic/CCT Research
state: Nebraska
city: Norfolk
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Norfolk
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research, Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Wake Research - Clinical Research Center of Nevada, LLC
state: Nevada
city: Las Vegas
country: United States
facility: Wake Research - Clinical Research Center of Nevada, LLC
state: Nevada
city: Raritan
country: United States
facility: Amici Clinical Research LLC
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Warren
country: United States
facility: IMA Clinical Research Warren
state: New Jersey
city: Gallup
country: United States
facility: Gallup Indian Medical Center
state: New Mexico
city: Gallup
country: United States
facility: Johns Hopkins Center for American Indian Health
state: New Mexico
city: Shiprock
country: United States
facility: Johns Hopkins Center for American Indian Health
state: New Mexico
city: Shiprock
country: United States
facility: Northern Navajo Medical Center
state: New Mexico
city: Binghamton
country: United States
facility: Meridian Clinical Research LLC
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital Infectious Disease
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center- Kari Steinmetz
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Vestal
country: United States
facility: Meridian Clinical Research, LLC
state: New York
city: Cary
country: United States
facility: Accellacare
state: North Carolina
city: Charlotte
country: United States
facility: Accellacare
state: North Carolina
city: Charlotte
country: United States
facility: Accellacare
state: North Carolina
city: Durham
country: United States
facility: Duke Vaccine and Trials Unit
state: North Carolina
city: Greensboro
country: United States
facility: PharmQuest Life Sciences, LLC
state: North Carolina
city: Hickory
country: United States
facility: Accellacare
state: North Carolina
city: Raleigh
country: United States
facility: Accellacare
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc.
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc.
state: North Carolina
city: Salisbury
country: United States
facility: Accellacare - Salisbury
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare (formerly PMG Research of Wilmington, LLC)
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare
state: North Carolina
city: Winston-Salem
country: United States
facility: Accellacare
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research
state: North Dakota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Meridian Clinical Research, LLC
state: Ohio
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd.
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Meridian Clinical Research
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: VA Northeast Ohio Healthcare System
state: Ohio
city: Cleveland
country: United States
facility: Velocity Clinical Research, Cleveland
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Inc
state: Ohio
city: Dayton
country: United States
facility: Dayton Clinical Research
state: Ohio
city: Dayton
country: United States
facility: Dayton Clinical Research
state: Ohio
city: Dayton
country: United States
facility: PriMED Clinical Research
state: Ohio
city: Dayton
country: United States
facility: PriMED Clinical Research
state: Ohio
city: South Euclid
country: United States
facility: Senders Pediatrics
state: Ohio
city: Norman
country: United States
facility: Lynn Institute of Norman
state: Oklahoma
city: Portland
country: United States
facility: Kaiser Permanente Center for Health Research
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Health Network/Network Office of Research and Innovation
state: Pennsylvania
city: East Greenwich
country: United States
facility: Velocity Clinical Research, Providence
state: Rhode Island
city: Little River
country: United States
facility: Main Street Physician's Care
state: South Carolina
city: Bristol
country: United States
facility: Holston Medical Group
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research - Weisgarber Medical Park
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates Inc
state: Tennessee
city: Tullahoma
country: United States
facility: Trinity Clinical Research
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Austin
country: United States
facility: ARC Clinical Research at Four Points
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A
state: Texas
city: Fort Worth
country: United States
facility: Ventavia Research Group
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research
state: Texas
city: Houston
country: United States
facility: HG Pediatrics
state: Texas
city: Houston
country: United States
facility: Renu Garg, MD Pediatrics
state: Texas
city: Houston
country: United States
facility: Van Tran Family Practice
state: Texas
city: Houston
country: United States
facility: Ventavia Research Group, LLC
state: Texas
city: Houston
country: United States
facility: DM Clinical Research-Bellaire
state: Texas
city: Keller
country: United States
facility: SCR of Texas, LLC
state: Texas
city: Keller
country: United States
facility: Ventavia Research Group
state: Texas
city: Mesquite
country: United States
facility: SMS Clinical Research
state: Texas
city: Pearland
country: United States
facility: LinQ Research, LLC
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: San Antonio
country: United States
facility: IMA Clinical Research San Antonio
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic
state: Utah
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic South
state: Utah
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)
state: Virginia
city: Midlothian
country: United States
facility: Virginia Research Center
state: Virginia
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital
state: Washington
city: Salvador
country: Brazil
facility: Obras Sociais Irma Dulce
state: Bahia
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica
city: Edmonton
country: Canada
facility: MIC Medial Imaging Consultants
state: Alberta
city: Frankfurt
country: Germany
facility: Studienzentrum Dr. Keller
city: Frankfurt
country: Germany
facility: IKF Pneumologie GmbH & Co. KG
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Hamerkaz
city: Ramat Gan
country: Israel
facility: The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric
state: Hamerkaz
city: East London
country: South Africa
facility: Synergy Biomed Research Institute
state: Eastern CAPE
city: Benoni
country: South Africa
facility: Worthwhile Clinical Trials
state: Gauteng
city: Johannesburg
country: South Africa
facility: Newtown Clinical Research
state: Gauteng
city: Kempton Park
country: South Africa
facility: Clinresco Centres
state: Gauteng
city: Midrand
country: South Africa
facility: Dr A Jacovides & Partners Inc.
state: Gauteng
city: Pretoria
country: South Africa
facility: Botho Ke Bontle Health Services PTY LTD
state: Gauteng
city: Thabazimbi
country: South Africa
facility: Limpopo Clinical Research Initiative
state: Limpopo
city: Cape Town
country: South Africa
facility: TREAD Research
state: Western CAPE
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre
state: Western CAPE
city: Pretoria
country: South Africa
facility: Jongaie Research
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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, Tureci O, Lagkadinou E, Tresnan DB, Dormitzer PR, Sahin 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.