MedPath

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

Phase 3
Completed
Conditions
SARS-CoV-2 Infection
COVID-19
Interventions
Biological: BNT162b2
Other: Placebo
Biological: BNT162b2 OMI
Biological: Combination BNT162b2 and BNT162b2 OMI
Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI
Registration Number
NCT04955626
Lead Sponsor
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 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 available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16385
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
60 µg doseBNT162b21 dose
10 µg doseBNT162b21 dose
PlaceboPlacebo1 dose
30 µg doseBNT162b21 dose
30 µg doseBNT162b2 OMI1 dose
30 µg doseCombination BNT162b2 and BNT162b2 OMI1 dose
60 µg doseBNT162b2 OMI1 dose
60 µg doseCombination (Bivalent) BNT162b2 and BNT162b2 OMI1 dose
30 µg doseCombination (Bivalent) BNT162b2 and BNT162b2 OMI1 dose
60 µg doseCombination BNT162b2 and BNT162b2 OMI1 dose
Primary Outcome Measures
NameTimeMethod
SSA - Percentage of participants reporting serious adverse eventsfrom the booster dose to 6 months after the booster dose

As elicited by investigational site staff

SSB - Percentage of participants with elevated troponin I levelsthrough 1 month after the second vaccination

Troponin I level

SSB - Percentage of participants reporting adverse eventswithin 1 month after each vaccination

As elicited by investigational site staff

SSB - Percentage of participants reporting serious adverse eventswithin 1 month after each vaccination

As elicited by investigational site staff

SSA - Confirmed COVID-19 incidence in participants without evidence of past SARS-CoV-2 infectionfrom 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 infectionfrom 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 eventsfrom the booster dose to 1 month after the booster dose

As elicited by investigational site staff

SSB - Percentage of participants reporting local reactionsFor 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 eventsFor 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.

SSC - Percentage of participants reporting adverse eventsfrom the booster dose to 1 month after the booster dose

As elicited by investigational site staff

SSC - Percentage of participants reporting local reactionsFor 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 eventsFor 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 - 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 C4591001At baseline (before the third dose), 1 month and 6 months after the third dose

GMTs at each time point

GMFRs from baseline (before the third dose) to each subsequent time point after the third dose

Percentage of participants with seroresponse at each time point after the third dose

SSC - Percentage of participants reporting serious adverse eventsfrom the booster dose to 6 months after the booster dose

As elicited by investigational site staff

SSD - Percentage of participants reporting systemic eventsFor 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 local reactionsFor 7 days following each vaccination

Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

SSD - Percentage of participants reporting adverse eventsfrom 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 eventsfrom 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 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 participants1 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 participants from the C4591001 study1 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 participants 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 participants selected from the C4591001 study

SSE - Percentage of participants reporting local reactionsFor 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 eventsFor 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 serious adverse eventsfrom the study vaccination through 6 months after the study vaccination

As elicited by investigational site staff

SSF - Percentage of participants reporting serious adverse eventsfrom the study vaccination through 6 months after the 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 participants1 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 participants1 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

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 age1 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 age1 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 - 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 age1 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 - Percentage of participants reporting adverse eventsfrom the study vaccination through 1 month 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)Before and 3 days after study vaccination

Troponin I level

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 age1 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 reactionsFor 7 days following the study vaccination

Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

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 participantsAt 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

GMRs of Omicron and reference-strain neutralizing titers at each time point after the study vaccination between different vaccine groups

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 age1 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 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age1 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 - 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 age1 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 age1 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

SSF - Percentage of participants reporting systemic eventsFor 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 eventsfrom the study vaccination through 1 month after the study vaccination

As elicited by investigational site staff

Secondary Outcome Measures
NameTimeMethod
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 participants1 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

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 age1 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 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 age1 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

SSA - Confirmed severe COVID-19 (based on CDC definition) in participants without evidence of past SARS-CoV-2 infectionfrom 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

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 age1 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

SSA - Confirmed severe COVID-19 (based on FDA definition) in participants with and without evidence of past SARS-CoV-2 infectionfrom 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 to BNT162b2 10 µg and 30 µg given as the third dose in participants 12 through 17 years of ageAt baseline (before the third dose) and 7 days after the third dose

GMTs at each time point

GMFRs from baseline (before the third dose) to 7 days after the third dose

Percentage of participants with seroresponse at 7 days after the third dose

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 participants1 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

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 age1 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 - 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 age1 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

SSA - Confirmed severe COVID-19 (based on FDA definition) period in participants without evidence of past SARS-CoV-2 infectionfrom 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 infectionfrom 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

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 participants1 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 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 study1 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 participants 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 participants 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 participants selected from the C4591001 study1 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 participants selected from the C4591001 study

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 age1 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

Trial Locations

Locations (140)

Wenatchee Valley Hospital

🇺🇸

Wenatchee, Washington, United States

Tiervlei Trial Centre

🇿🇦

Cape Town, Western CAPE, South Africa

Kaiser Permenente Medical Center Infectious Disease

🇺🇸

Los Angeles, California, United States

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

Obras Sociais Irma Dulce

🇧🇷

Salvador, Bahia, Brazil

HOPE Research Institute

🇺🇸

Phoenix, Arizona, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Sterling Research Group, Ltd.

🇺🇸

Cincinnati, Ohio, United States

Cincinnati Children's Hospital

🇺🇸

Cincinnati, Ohio, United States

Kaiser Permanente Center for Health Research

🇺🇸

Portland, Oregon, United States

Renu Garg, MD Pediatrics

🇺🇸

Houston, Texas, United States

Van Tran Family Practice

🇺🇸

Houston, Texas, United States

Ventavia Research Group, LLC

🇺🇸

Houston, Texas, United States

DM Clinical Research-Bellaire

🇺🇸

Houston, Texas, United States

Clinical Trials of Texas, LLC

🇺🇸

San Antonio, Texas, United States

North Alabama Research Center

🇺🇸

Athens, Alabama, United States

Alliance for Multispecialty Research, LLC

🇺🇸

Wichita, Kansas, United States

Accel Research Sites - Birmingham Clinical Research Unit

🇺🇸

Birmingham, Alabama, United States

Whiteriver Indian Hospital- Garrett Building

🇺🇸

Whiteriver, Arizona, United States

Kaiser Permanente

🇺🇸

Los Angeles, California, United States

Whiteriver Indian Hospital

🇺🇸

Whiteriver, Arizona, United States

Anaheim Clinical Trials, LLC

🇺🇸

Anaheim, California, United States

Collaborative Neuroscience Research, LLC

🇺🇸

Long Beach, California, United States

Clinical Research Atlanta

🇺🇸

Stockbridge, Georgia, United States

Velocity Clinical Research, Sioux City

🇺🇸

Sioux City, Iowa, United States

IACT Health

🇺🇸

Columbus, Georgia, United States

PharmQuest Life Sciences, LLC

🇺🇸

Greensboro, North Carolina, United States

MedPharmics, LLC

🇺🇸

Gulfport, Mississippi, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

VA Northeast Ohio Healthcare System

🇺🇸

Cleveland, Ohio, United States

Dayton Clinical Research

🇺🇸

Dayton, Ohio, United States

Lehigh Valley Health Network/Network Office of Research and Innovation

🇺🇸

Allentown, Pennsylvania, United States

Accellacare (formerly PMG Research of Wilmington, LLC)

🇺🇸

Wilmington, North Carolina, United States

Main Street Physician's Care

🇺🇸

Little River, South Carolina, United States

PriMED Clinical Research

🇺🇸

Dayton, Ohio, United States

Clinical Neuroscience Solutions Inc.

🇺🇸

Memphis, Tennessee, United States

Accellacare - Salisbury

🇺🇸

Salisbury, North Carolina, United States

Lynn Institute of Norman

🇺🇸

Norman, Oklahoma, United States

M3 Wake Research, Inc.

🇺🇸

Raleigh, North Carolina, United States

Senders Pediatrics

🇺🇸

South Euclid, Ohio, United States

Velocity Clinical Research, Providence

🇺🇸

East Greenwich, Rhode Island, United States

Aventiv Research Inc

🇺🇸

Columbus, Ohio, United States

Lillestol Research

🇺🇸

Fargo, North Dakota, United States

University Hospitals Cleveland Medical Center

🇺🇸

Cleveland, Ohio, United States

Alliance for Multispecialty Research - Weisgarber Medical Park

🇺🇸

Knoxville, Tennessee, United States

Trinity Clinical Research

🇺🇸

Tullahoma, Tennessee, United States

Benchmark Research

🇺🇸

Fort Worth, Texas, United States

DM Clinical Research

🇺🇸

Tomball, Texas, United States

HG Pediatrics

🇺🇸

Houston, Texas, United States

J. Lewis Research, Inc. / Foothill Family Clinic

🇺🇸

Salt Lake City, Utah, United States

J. Lewis Research, Inc. / Foothill Family Clinic South

🇺🇸

Salt Lake City, Utah, United States

Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)

🇺🇸

Annandale, Virginia, United States

SMS Clinical Research

🇺🇸

Mesquite, Texas, United States

Ventavia Research Group

🇺🇸

Keller, Texas, United States

SCR of Texas, LLC

🇺🇸

Keller, Texas, United States

LinQ Research, LLC

🇺🇸

Pearland, Texas, United States

IMA Clinical Research San Antonio

🇺🇸

San Antonio, Texas, United States

Dr A Jacovides & Partners Inc.

🇿🇦

Midrand, Gauteng, South Africa

IKF Pneumologie GmbH & Co. KG

🇩🇪

Frankfurt, Germany

Clinresco Centres

🇿🇦

Kempton Park, Gauteng, South Africa

Virginia Research Center

🇺🇸

Midlothian, Virginia, United States

Studienzentrum Dr. Keller

🇩🇪

Frankfurt, Germany

Sheba Medical Center

🇮🇱

Ramat Gan, Hamerkaz, Israel

Botho Ke Bontle Health Services PTY LTD

🇿🇦

Pretoria, Gauteng, South Africa

Velocity Clinical Research, Cleveland

🇺🇸

Cleveland, Ohio, United States

UC Davis Medical Center

🇺🇸

Sacramento, California, United States

Quality Clinical Research

🇺🇸

Omaha, Nebraska, United States

Medical Affiliated Research Center

🇺🇸

Huntsville, Alabama, United States

Johns Hopkins Center for American Indian Health

🇺🇸

Shiprock, New Mexico, United States

The Pain Center of Arizona

🇺🇸

Phoenix, Arizona, United States

Kaiser Permanente Los Angeles Medical Center

🇺🇸

Los Angeles, California, United States

Paradigm Clinical Research Centers, Inc

🇺🇸

Redding, California, United States

Velocity Clinical Research, Westlake

🇺🇸

Los Angeles, California, United States

California Research Foundation

🇺🇸

San Diego, California, United States

Velocity Clinical Research, North Hollywood

🇺🇸

North Hollywood, California, United States

Kaiser Permanente Oakland

🇺🇸

Oakland, California, United States

Kaiser Permanente Santa Clara

🇺🇸

Santa Clara, California, United States

Diablo Clinical Research, Inc.

🇺🇸

Walnut Creek, California, United States

Lynn Institute of Denver

🇺🇸

Aurora, Colorado, United States

Bayview Research Group, LLC

🇺🇸

Valley Village, California, United States

Clinical Research Consulting

🇺🇸

Milford, Connecticut, United States

Indago Research & Health Center, Inc

🇺🇸

Hialeah, Florida, United States

Research Centers of America ( Hollywood )

🇺🇸

Hollywood, Florida, United States

Jacksonville Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

Clinical Neuroscience Solutions, Inc. dba CNS Healthcare

🇺🇸

Memphis, Tennessee, United States

Acevedo Clinical Research Associates

🇺🇸

Miami, Florida, United States

Meridian Clinical Research, LLC

🇺🇸

Cincinnati, Ohio, United States

Solaris Clinical Research

🇺🇸

Meridian, Idaho, United States

University of Iowa

🇺🇸

Iowa City, Iowa, United States

Kentucky Pediatric/ Adult Research

🇺🇸

Bardstown, Kentucky, United States

Johns Hopkins Bayview Medical Center

🇺🇸

Baltimore, Maryland, United States

Louisiana State University Health Sciences Shreveport

🇺🇸

Shreveport, Louisiana, United States

University of Massachusetts Chan Medical School

🇺🇸

Worcester, Massachusetts, United States

Michigan Center of Medical Research (MICHMER)

🇺🇸

Farmington Hills, Michigan, United States

Sundance Clinical Research

🇺🇸

Saint Louis, Missouri, United States

Clinical Research Professionals

🇺🇸

Chesterfield, Missouri, United States

Bozeman Health Deaconess Hospital d/b/a Bozeman Health Clinical Research

🇺🇸

Bozeman, Montana, United States

Methodist Physicians Clinic/CCT Research

🇺🇸

Fremont, Nebraska, United States

Velocity Clinical Research, Omaha

🇺🇸

Omaha, Nebraska, United States

Bozeman Health Deaconess Hospital

🇺🇸

Bozeman, Montana, United States

Clinical Research Center of Nevada

🇺🇸

Las Vegas, Nevada, United States

Meridian Clinical Research

🇺🇸

Cincinnati, Ohio, United States

Wake Research - Clinical Research Center of Nevada, LLC

🇺🇸

Las Vegas, Nevada, United States

Amici Clinical Research LLC

🇺🇸

Raritan, New Jersey, United States

South Jersey Infectious Disease

🇺🇸

Somers Point, New Jersey, United States

IMA Clinical Research Warren

🇺🇸

Warren, New Jersey, United States

Northern Navajo Medical Center

🇺🇸

Shiprock, New Mexico, United States

NYU Langone Health

🇺🇸

New York, New York, United States

Gallup Indian Medical Center

🇺🇸

Gallup, New Mexico, United States

Meridian Clinical Research LLC

🇺🇸

Binghamton, New York, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

Rochester Clinical Research, Inc.

🇺🇸

Rochester, New York, United States

University of Rochester Medical Center- Kari Steinmetz

🇺🇸

Rochester, New York, United States

Accellacare

🇺🇸

Winston-Salem, North Carolina, United States

Rochester General Hospital Infectious Disease

🇺🇸

Rochester, New York, United States

SUNY Upstate Medical University

🇺🇸

Syracuse, New York, United States

Duke Vaccine and Trials Unit

🇺🇸

Durham, North Carolina, United States

Clinical Research Associates Inc

🇺🇸

Nashville, Tennessee, United States

Holston Medical Group

🇺🇸

Kingsport, Tennessee, United States

North Texas Infectious Diseases Consultants, P.A

🇺🇸

Dallas, Texas, United States

CEPIC - Centro Paulista de Investigação Clínica

🇧🇷

São Paulo, Brazil

Clinical Trials of Texas, Inc.

🇺🇸

San Antonio, Texas, United States

Benaroya Research Institute at Virginia Mason

🇺🇸

Seattle, Washington, United States

Newtown Clinical Research

🇿🇦

Johannesburg, Gauteng, South Africa

The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric

🇮🇱

Ramat Gan, Hamerkaz, Israel

Jongaie Research

🇿🇦

Pretoria, South Africa

Limpopo Clinical Research Initiative

🇿🇦

Thabazimbi, Limpopo, South Africa

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

Yale-New Haven Hospital

🇺🇸

New Haven, Connecticut, United States

Yale Center for Clinical Investigation

🇺🇸

New Haven, Connecticut, United States

Clinical Neuroscience Solutions, Inc.

🇺🇸

Orlando, Florida, United States

TREAD Research

🇿🇦

Cape Town, Western CAPE, South Africa

Synergy Biomed Research Institute

🇿🇦

East London, Eastern CAPE, South Africa

East-West Medical Research Institute

🇺🇸

Honolulu, Hawaii, United States

Ochsner Clinic Foundation

🇺🇸

New Orleans, Louisiana, United States

ARC Clinical Research at Four Points

🇺🇸

Austin, Texas, United States

Tekton Research, Inc

🇺🇸

Austin, Texas, United States

MIC Medial Imaging Consultants

🇨🇦

Edmonton, Alberta, Canada

University of Rochester

🇺🇸

Rochester, New York, United States

Worthwhile Clinical Trials

🇿🇦

Benoni, Gauteng, South Africa

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