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

Sponsor

BioNTech SE (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04955626

Collaborator

Pfizer (Industry)

10,000

Enrollment

159

Locations

Arms

26.7

Anticipated Duration (Months)

62.9

Patients Per Site

2.4

Patients Per Site Per Month

Study Details

Study Description

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 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 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 third dose approximately 5 months later.
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 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

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2 Infection COVID-19	Biological: BNT162b2 Other: Placebo Biological: BNT162b2 OMI Biological: Combination BNT162b2 and BNT162b2 OMI Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

A PHASE 3 MASTER PROTOCOL TO EVALUATE ADDITIONAL DOSE(S) OF BNT162B2 IN HEALTHY INDIVIDUALS PREVIOUSLY VACCINATED WITH BNT162B2

Actual Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Sep 22, 2023

Anticipated Study Completion Date :

Sep 22, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 10 µg dose 1 dose	Biological: BNT162b2 Intramuscular Injection
Placebo Comparator: Placebo 1 dose	Other: Placebo Intramuscular Injection
Experimental: 30 µg dose 1 dose	Biological: BNT162b2 Intramuscular Injection Biological: BNT162b2 OMI Intramuscular Injection Biological: Combination BNT162b2 and BNT162b2 OMI 30-µg (15-µg each) or 60-µg (30-µg each) Site prepared dosing suspension from 1 vial each of diluted BNT162b2 and BNT162b2 OMI Intramuscular Injection Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI 30-µg (15-µg each) or 60-µg (30-µg each) Preformulated bivalent mixture (no dilution required) presented in a single vial Intramuscular Injection
Experimental: 60 µg dose 1 dose	Biological: BNT162b2 Intramuscular Injection Biological: BNT162b2 OMI Intramuscular Injection Biological: Combination BNT162b2 and BNT162b2 OMI 30-µg (15-µg each) or 60-µg (30-µg each) Site prepared dosing suspension from 1 vial each of diluted BNT162b2 and BNT162b2 OMI Intramuscular Injection Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI 30-µg (15-µg each) or 60-µg (30-µg each) Preformulated bivalent mixture (no dilution required) presented in a single vial Intramuscular Injection

Outcome Measures

Primary Outcome Measures

SSA - Confirmed COVID-19 incidence in participants without evidence of past SARS-CoV-2 infection [from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months]
per 1000 person-years of blinded follow-up
SSA - Confirmed COVID-19 incidence in participants with and without evidence of past SARS-CoV-2 infection [from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months]
per 1000 person-years of blinded follow-up
SSA - Percentage of participants reporting adverse events [from the booster dose to 1 month after the booster dose]
As elicited by investigational site staff
SSA - Percentage of participants reporting serious adverse events [from the booster dose to 6 months after the booster dose]
As elicited by investigational site staff
SSB - Percentage of participants with elevated troponin I levels [through 1 month after the second vaccination]
Troponin I level
SSB - Percentage of participants reporting local reactions [For 7 days following each vaccination]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
SSB - Percentage of participants reporting systemic events [For 7 days following each vaccination]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
SSB - Percentage of participants reporting adverse events [within 1 month after each vaccination]
As elicited by investigational site staff
SSB - Percentage of participants reporting serious adverse events [within 1 month after each vaccination]
As elicited by investigational site staff
SSC - Percentage of participants reporting local reactions [For 7 days following the booster dose]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
SSC - Percentage of participants reporting systemic events [For 7 days following the booster dose]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
SSC - Percentage of participants reporting adverse events [from the booster dose to 1 month after the booster dose]
As elicited by investigational site staff
SSC - Percentage of participants reporting serious adverse events [from the booster dose to 6 months after the booster dose]
As elicited by investigational site staff
SSC - For each of the 2 age groups (12 through 17, and ≥56 years of age): Demonstrate immunobridging of immune response of D3 of BNT162b2 at 30 µg compared to after D2 in age-matched participants from the C4591001 study [1 month after the booster (third) dose, and 1 month after the second dose for participants in the control group]
GMR, estimated by the ratio of the GMTs of SARS-CoV-2 neutralizing titers at 1 month after the third dose in participants who received a booster (third) dose of BNT162b2 at 30 µg to those at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study. The difference in the percentage of participants with seroresponse at 1 month after the third dose in participants who received a booster (third) dose of BNT162b2 at 30 µg and at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study
SSC - For each of the 4 age groups (12 through 17, 18 through 30, 31 through 55, and ≥56 years of age): Demonstrate immunobridging of immune response of D3 of BNT162b2 at 10 µg compared to after D2 in age-matched participants from the C4591001 study [1 month after the booster (third) dose, and 1 month after the second dose for participants in the control group]
GMR, estimated by the ratio of the GMTs of SARS-CoV-2 neutralizing titers at 1 month after the third dose in participants who received a booster (third) dose of BNT162b2 at 10 µg to those at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study. The difference in percentage of participants with seroresponse at 1 month after the third dose in participants who received a booster (third) dose of BNT162b2 at 10 µg and at 1 month after the second dose in age-matched participants randomly selected from the C4591001 study
SSD - Percentage of participants reporting local reactions [For 7 days following each vaccination]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
SSD - Percentage of participants reporting systemic events [For 7 days following each vaccination]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
SSD - Percentage of participants reporting adverse events [from the first study vaccination (received in this study) through 1 month after the last study vaccination]
As elicited by investigational site staff
SSD - Percentage of participants reporting serious adverse events [from the first study vaccination (received in this study) through 6 months after the last study vaccination]
As elicited by investigational site staff
SSD-Superiority with respect to neutralizing titers and noninferiority with respect to seroresponse rate of the anti-Omi immune response after 1 dose of BNT162b2 OMI compared to after 1 dose of BNT162b2 given as D3 in BNT162b2-experienced participants [1 month after receipt of 1 dose of study intervention]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of BNT162b2 OMI and at 1 month after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants
SSD-Superiority with respect to neutralizing titers and noninferiority with respect to seroresponse of anti-Omi immune response after 2 doses BNT162b2 OMI given as D3+D4 compared to after 1 dose BNT162b2 given as D3 in BNT162b2-experienced participants [1 month after receipt of 1 or 2 doses of intervention as appropriate]
GMR of the Omicron-neutralizing titers at 1 month after 2 doses of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the third (and fourth) dose in BNT162b2-experienced participants The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 2 doses of BNT162b2 OMI and at 1 month after 1 dose of BNT162b2 given as the third (and fourth) dose in BNT162b2-experienced participants
SSD-Superiority with respect to neutralizing titer and noninferiority with respect to seroresponse rate of the anti-Omi immune response after 1 dose BNT162b2 OMI compared to after 1 dose BNT162b2 given as the D4 in BNT162b2-experienced participants [1 month after receipt of 1 dose of study intervention]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the fourth dose in BNT162b2-experienced participants The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of BNT162b2 OMI and at 1 month after 1 dose of BNT162b2 given as the fourth dose in BNT162b2-experienced participants
SSD-Superiority with respect to neutralizing titer and noninferiority with respect to seroresponse rate of the anti-Omi immune response after 2 doses BNT162b2 OMI compared to after 2 doses BNT162b2 in age-matched participants from the C4591001 study [1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate]
GMR of the Omicron-neutralizing titers 1 month after the second dose of BNT162b2 OMI to 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after the second dose of BNT162b2 OMI and at 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study
SSE - Percentage of participants reporting local reactions [For 7 days following the study vaccination]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
SSE - Percentage of participants reporting systemic events [For 7 days following the study vaccination]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
SSE - Percentage of participants reporting adverse events [from the study vaccination through 1 month after the study vaccination]
As elicited by investigational site staff
SSE - Percentage of participants reporting serious adverse events [from the study vaccination through 6 months after the study vaccination]
As elicited by investigational site staff
SSE - Percentage of participants with elevated troponin I levels (18-55 years of age, sentinel cohort only) [Before and 3 days after study vaccination]
Troponin I level
SSE - Superiority of neutralizing titer after 1 dose of BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - Noninferiority of anti-Omicron immune response after 1 dose of BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of BNT162b2 OMI 30 µg and at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - Superiority of neutralizing titer after 1 dose of BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - Noninferiority of anti-Omicron immune response after 1 dose of BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of BNT162b2 OMI 60 µg and at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - Superiority of neutralizing titer after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - Noninferiority of anti-Omicron immune response after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg and at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - Superiority of neutralizing titer after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2
SSE - Noninferiority of anti-Omicron immune response after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg and at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSF - Percentage of participants reporting local reactions [For 7 days following the study vaccination]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
SSF - Percentage of participants reporting systemic events [For 7 days following the study vaccination]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
SSF - Percentage of participants reporting adverse events [from the study vaccination through 1 month after the study vaccination]
As elicited by investigational site staff
SSF - Percentage of participants reporting serious adverse events [from the study vaccination through 6 months after the study vaccination]
As elicited by investigational site staff
SSF - To describe the immune response to BNT162b2 (30 µg or 60 µg), BNT162b2 OMI (30 µg or 60 µg), and a combination of BNT162b2 and BNT162b2 OMI (30 µg or 60 µg) given as a fourth dose in BNT162b2-experienced participants [At each time point]
GMT of Omicron and reference-strain neutralizing titers GMFRs of Omicron and reference-strain neutralizing titers from before the study vaccination to subsequent time points Percentages of participants with seroresponse for Omicron and reference-strain neutralizing titers at each time point

Secondary Outcome Measures

SSA - Confirmed severe COVID-19 (based on FDA definition) period in participants without evidence of past SARS-CoV-2 infection [from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months]
per 1000 person-years of blinded follow-up
SSA - Confirmed severe COVID-19 (based on FDA definition) in participants with and without evidence of past SARS-CoV-2 infection [from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months]
per 1000 person-years of blinded follow-up
SSA - Confirmed severe COVID-19 (based on CDC definition) in participants without evidence of past SARS-CoV-2 infection [from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months]
per 1000 person-years of blinded follow-up
SSA - Confirmed severe COVID-19 (based on CDC definition) in participants with and without evidence of past SARS-CoV-2 infection [from 7 days after the booster dose through the blinded follow-up period, which may be from 2 to 12 months]
per 1000 person-years of blinded follow-up
SSA - Incidence of asymptomatic SARS-CoV-2 infection based on N-binding antibody in participants without evidence of past SARS-CoV-2 infection [From the booster dose through the blinded follow-up period, which may be from 2 to 12 months]
per 1000 person-years of follow-up
SSC - Immune responses induced by a booster (third) dose of BNT162b2 at 10 µg and 30 µg [Through 1 year after the booster (third) dose]
GMTs of SARS-CoV-2 neutralizing titers GMFRs of SARS-CoV-2 neutralizing titers
SSD - The "super" superiority of the anti-Omicron immune response after 1 dose of BNT162b2 OMI compared to after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants [1 month after receipt of 1 dose of study intervention]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants
SSD - The "super" superiority of the anti-Omicron immune response after 2 doses of BNT162b2 OMI given as the third and fourth doses compared to after 1 dose of BNT162b2 given as the third dose in BNT162b2-experienced participants [1 month after receipt of 1 or 2 doses of intervention as appropriate]
GMR of the Omicron-neutralizing titers at 1 month after 2 doses of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the third (and fourth) dose in BNT162b2-experienced participants
SSD - The "super" superiority of the anti-Omicron immune response after 1 dose of BNT162b2 OMI compared to after 1 dose of BNT162b2 given as the fourth dose in BNT162b2-experienced participants [1 month after receipt of 1 dose of study intervention]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI to those at 1 month after 1 dose of BNT162b2 given as the fourth dose in BNT162b2-experienced participants
SSD - The noninferiority of the anti-Omicron immune response after 2 doses of BNT162b2 OMI compared to the anti-reference-strain immune response after 2 doses of BNT162b2 in age-matched participants randomly selected from the C4591001 study [1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate]
GMR of the Omicron-neutralizing titers 1 month after the second dose of BNT162b2 OMI to the reference-strain-neutralizing titers 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study The difference in percentages of participants with seroresponse to the Omicron strain at 1 month after the second dose of BNT162b2 OMI and seroresponsea to the reference strain at 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study
SSD - The "super" superiority of the anti-Omicron immune response after 2 doses of BNT162b2 OMI compared to after 2 doses of BNT162b2 in age-matched participants randomly selected from the C4591001 study [1 month after receipt of the second dose of BNT162b2 OMI or BNT162b2 as appropriate]
GMR of the Omicron-neutralizing titers 1 month after the second dose of BNT162b2 OMI to 1 month after the second dose of BNT162b2 in age-matched participants randomly selected from the C4591001 study
SSE - Noninferiority of anti-reference-strain immune response after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the reference strain-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - Noninferiority of anti-reference strain immune response after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the reference strain-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - The "super" superiority of anti-Omicron immune responses after 1 dose of BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - The "super" superiority of anti-Omicron immune responses after 1 dose of BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - The "super" superiority of anti-Omicron immune responses after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 30 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants
SSE - The "super" superiority of anti-Omicron immune responses after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg compared to after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants >55 years of age [1 month after receipt of 1 dose of study intervention given as a fourth dose]
GMR of the Omicron-neutralizing titers at 1 month after 1 dose of bivalent BNT162b2 and BNT162b2 OMI at 60 µg to those at 1 month after 1 dose of BNT162b2 at 30 µg given as a fourth dose in BNT162b2-experienced participants

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 150 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 2 doses of BNT162b2 30 µg.
Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.

Substudy C

Inclusion Criteria:

Male or female participants ≥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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Alabama Research Center	Athens	Alabama	United States	35611
2	Accel Research Sites - Birmingham Clinical Research Unit	Birmingham	Alabama	United States	35216
3	Medical Affiliated Research Center	Huntsville	Alabama	United States	35801
4	Alliance for Multispecialty Research, LLC	Mobile	Alabama	United States	36608
5	Johns Hopkins Center for American Indian Health	Chinle	Arizona	United States	86503
6	Hope Research Institute	Phoenix	Arizona	United States	85018
7	The Pain Center of Arizona	Phoenix	Arizona	United States	85018
8	HOPE Research Institute	Phoenix	Arizona	United States	85023
9	Alliance for Multispecialty Research, LLC	Tempe	Arizona	United States	85281
10	Johns Hopkins Center for American Indian Health	Whiteriver	Arizona	United States	85941
11	Whiteriver Indian Hospital- Garrett Building	Whiteriver	Arizona	United States	85941
12	Whiteriver Indian Hospital	Whiteriver	Arizona	United States	85941
13	CenExel ACT	Anaheim	California	United States	92801
14	Collaborative Neuroscience Research, LLC. - Investigator Site File Location	Garden Grove	California	United States	92845
15	Collaborative Neuroscience Research, LLC	Long Beach	California	United States	90806
16	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
17	Kaiser Permanente	Los Angeles	California	United States	90027
18	Kaiser Permenente Medical Center Infectious Disease	Los Angeles	California	United States	90027
19	Velocity Clinical Research, Westlake	Los Angeles	California	United States	90057
20	Velocity Clinical Research, North Hollywood	North Hollywood	California	United States	91606
21	Kaiser Permanente Oakland	Oakland	California	United States	94611
22	Paradigm Clinical Research Centers, Inc	Redding	California	United States	96001
23	UC Davis Medical Center	Sacramento	California	United States	95817
24	California Research Foundation	San Diego	California	United States	92123
25	Kaiser Permanente Santa Clara	Santa Clara	California	United States	95051
26	Bayview Research Group, LLC	Valley Village	California	United States	91607
27	Diablo Clinical Research, Inc.	Walnut Creek	California	United States	94598
28	Lynn Institute of Denver	Aurora	Colorado	United States	80012
29	Clinical Research Consulting	Milford	Connecticut	United States	06460
30	Yale University School of Medicine	New Haven	Connecticut	United States	06510
31	Yale-New Haven Hospital	New Haven	Connecticut	United States	06511
32	Yale Center for Clinical Investigation	New Haven	Connecticut	United States	06519
33	Alliance for Multispecialty Research, LLC	Coral Gables	Florida	United States	33134
34	Indago Research & Health Center, Inc	Hialeah	Florida	United States	33012
35	Research Centers of America ( Hollywood )	Hollywood	Florida	United States	33024
36	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
37	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Jacksonville	Florida	United States	32256
38	Acevedo Clinical Research Associates	Miami	Florida	United States	33142
39	Clinical Neuroscience Solutions	Orlando	Florida	United States	32801
40	IACT Health	Columbus	Georgia	United States	31904
41	Meridian Clinical Research, LLC	Savannah	Georgia	United States	31406
42	Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
43	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
44	Solaris Clinical Research	Meridian	Idaho	United States	83646
45	University of Iowa	Iowa City	Iowa	United States	52242
46	Meridian Clinical Research, LLC	Sioux City	Iowa	United States	51106
47	Alliance for Multispecialty Research, LLC	Newton	Kansas	United States	67114
48	Alliance for Multispecialty Research, LLC	Wichita	Kansas	United States	67207
49	Kentucky Pediatric/ Adult Research	Bardstown	Kentucky	United States	40004
50	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
51	Louisiana State University Health Sciences Shreveport	Shreveport	Louisiana	United States	71101
52	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224
53	Boston Medical Center	Boston	Massachusetts	United States	02118
54	Investigational Pharmacy Service	Boston	Massachusetts	United States	02118
55	University of Massachusetts Chan Medical School	Worcester	Massachusetts	United States	01655
56	Michigan Center of Medical Research (MICHMER)	Farmington Hills	Michigan	United States	48334
57	MedPharmics, LLC	Gulfport	Mississippi	United States	39503
58	Clinical Research Professionals	Chesterfield	Missouri	United States	63005
59	Sundance Clinical Research	Saint Louis	Missouri	United States	63141
60	Bozeman Health Deaconess Hospital d/b/a Bozeman Health Clinical Research	Bozeman	Montana	United States	59715
61	Bozeman Health Deaconess Hospital	Bozeman	Montana	United States	59715
62	Methodist Physicians Clinic/CCT Research	Fremont	Nebraska	United States	68025
63	Meridian Clinical Research, LLC	Norfolk	Nebraska	United States	68701
64	Quality Clinical Research	Omaha	Nebraska	United States	68114
65	Meridian Clinical Research, LLC	Omaha	Nebraska	United States	68134
66	Clinical Research Center of Nevada	Las Vegas	Nevada	United States	89104
67	Wake Research - Clinical Research Center of Nevada, LLC	Las Vegas	Nevada	United States	89104
68	Amici Clinical Research LLC	Raritan	New Jersey	United States	08869
69	South Jersey Infectious Disease	Somers Point	New Jersey	United States	08244
70	Gallup Indian Medical Center	Gallup	New Mexico	United States	87301
71	Johns Hopkins Center for American Indian Health	Gallup	New Mexico	United States	87301
72	Johns Hopkins Center for American Indian Health	Shiprock	New Mexico	United States	87420
73	Northern Navajo Medical Center	Shiprock	New Mexico	United States	87420
74	Meridian Clinical Research LLC	Binghamton	New York	United States	13901
75	Meridian Clinical Research, LLC	Endwell	New York	United States	13760
76	NYU Langone Health	New York	New York	United States	10016
77	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
78	Rochester Clinical Research, Inc.	Rochester	New York	United States	14609
79	Rochester General Hospital Infectious Disease	Rochester	New York	United States	14621
80	SUNY Upstate Medical University	Syracuse	New York	United States	13215
81	Accellacare	Cary	North Carolina	United States	27518
82	Accellacare	Charlotte	North Carolina	United States	28209
83	Duke Vaccine and Trials Unit	Durham	North Carolina	United States	27703
84	PharmQuest	Greensboro	North Carolina	United States	27408
85	Accellacare	Hickory	North Carolina	United States	28601
86	Accellacare	Raleigh	North Carolina	United States	27609
87	M3 Wake Research, Inc.	Raleigh	North Carolina	United States	27612-8104
88	M3 Wake Research, Inc.	Raleigh	North Carolina	United States	27612
89	Accellacare - Salisbury	Salisbury	North Carolina	United States	28144
90	Accellacare (formerly PMG Research of Wilmington, LLC)	Wilmington	North Carolina	United States	28401
91	Accellacare	Wilmington	North Carolina	United States	28401
92	Accellacare	Winston-Salem	North Carolina	United States	27103
93	Lillestol Research	Fargo	North Dakota	United States	58104
94	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45206
95	Meridian Clinical Research, LLC	Cincinnati	Ohio	United States	45219
96	Sterling Research Group, Ltd.	Cincinnati	Ohio	United States	45219
97	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229-3039
98	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
99	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
100	Meridian Clinical Research	Cincinnati	Ohio	United States	45246
101	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
102	VA Northeast Ohio Healthcare System	Cleveland	Ohio	United States	44106
103	Velocity Clinical Research	Cleveland	Ohio	United States	44122
104	Aventiv Research Inc	Columbus	Ohio	United States	43213
105	Schear Family Practice Network	Dayton	Ohio	United States	45409
106	PriMED Clinical Research	Dayton	Ohio	United States	45419
107	Senders Pediatrics	South Euclid	Ohio	United States	44121
108	Lynn Institute of Norman	Norman	Oklahoma	United States	73072
109	Kaiser Permanente Northwest Center for Health Research	Portland	Oregon	United States	97227
110	Lehigh Valley Health Network/Network Office of Research and Innovation	Allentown	Pennsylvania	United States	18102
111	Velocity Clinical Research, Providence	East Greenwich	Rhode Island	United States	02818
112	Main Street Physician's Care	Little River	South Carolina	United States	29566
113	Holston Medical Group	Bristol	Tennessee	United States	37620
114	Holston Medical Group	Kingsport	Tennessee	United States	37660
115	Alliance for Multispecialty Research - Weisgarber Medical Park	Knoxville	Tennessee	United States	37909
116	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Memphis	Tennessee	United States	38119
117	Clinical Research Associates Inc	Nashville	Tennessee	United States	37203
118	Trinity Clinical Research	Tullahoma	Tennessee	United States	37388
119	Benchmark Research	Austin	Texas	United States	78705
120	ARC Clinical Research at Wilson Parke	Austin	Texas	United States	78726
121	Tekton Research, Inc.	Austin	Texas	United States	78745
122	North Texas Infectious Diseases Consultants, P.A	Dallas	Texas	United States	75246
123	Ventavia Research Group	Fort Worth	Texas	United States	76104
124	Benchmark Research	Fort Worth	Texas	United States	76135
125	HG Pediatrics	Houston	Texas	United States	77008
126	Renu Garg, MD Pediatrics	Houston	Texas	United States	77008
127	Van Tran Family Practice	Houston	Texas	United States	77008
128	Ventavia Research Group, LLC	Houston	Texas	United States	77008
129	Texas Center for Drug Development, Inc.	Houston	Texas	United States	77081
130	Ventavia Research Group	Keller	Texas	United States	76248
131	SMS Clinical Research	Mesquite	Texas	United States	75149
132	LinQ Research, LLC	Pearland	Texas	United States	77584
133	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
134	Clinical Trials of Texas, LLC	San Antonio	Texas	United States	78229
135	IMA Clinical Research San Antonio	San Antonio	Texas	United States	78229
136	DM Clinical Research	Tomball	Texas	United States	77375
137	J. Lewis Research, Inc. / Foothill Family Clinic	Salt Lake City	Utah	United States	84109
138	J. Lewis Research, Inc. / Foothill Family Clinic South	Salt Lake City	Utah	United States	84121
139	Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)	Annandale	Virginia	United States	22003
140	Virginia Research Center	Midlothian	Virginia	United States	23114
141	Benaroya Research Institute at Virginia Mason	Seattle	Washington	United States	98101
142	Wenatchee Valley Hospital	Wenatchee	Washington	United States	98801
143	Obras Sociais Irma Dulce	Salvador	Bahia	Brazil	40.415-006
144	CEPIC - Centro Paulista de Investigação Clínica	São Paulo		Brazil	04266-010
145	MIC Medial Imaging Consultants	Edmonton	Alberta	Canada	T5H 4B9
146	Studienzentrum Dr. Keller	Frankfurt		Germany	60389
147	IKF Pneumologie GmbH & Co. KG	Frankfurt		Germany	60596
148	Sheba Medical Center	Ramat Gan	Hamerkaz	Israel	5265601
149	Synergy Biomed Research Institute	East London	Eastern CAPE	South Africa	5201
150	Worthwhile Clinical Trials	Benoni	Gauteng	South Africa	1501
151	Newtown Clinical Research	Johannesburg	Gauteng	South Africa	2113
152	Clinresco Centres	Kempton Park	Gauteng	South Africa	1619
153	Dr A Jacovides & Partners Inc.	Midrand	Gauteng	South Africa	1685
154	Botho Ke Bontle Health Services PTY LTD	Pretoria	Gauteng	South Africa	0122
155	About Allergy	Pretoria	Gauteng	South Africa	0181
156	Limpopo Clinical Research Initiative	Thabazimbi	Limpopo	South Africa	0380
157	TREAD Research	Cape Town	Western CAPE	South Africa	7500
158	Tiervlei Trial Centre	Cape Town	Western CAPE	South Africa	7530
159	Jongaie Research	Pretoria		South Africa	0183