Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Individuals

Sponsor

BioNTech SE (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04368728

Collaborator

Pfizer (Industry)

46,949

Enrollment

166

Locations

Arms

45.3

Anticipated Duration (Months)

282.8

Patients Per Site

6.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals.

The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part.

The study will evaluate the safety, tolerability, and immunogenicity of 3 different

SARS-CoV-2 RNA vaccine candidates against COVID-19 and the efficacy of 1 candidate:

As a 2-dose (separated by 21 days) schedule;
At various different dose levels in Phase 1;
As a booster;
In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: ≥12 years of age [stratified as 12-15, 16-55 or >55 years of age]).

The candidate selected for efficacy evaluation in Phase 2/3 is BNT162b2 at a dose of 30 µg.

Participants who originally received placebo will be offered the opportunity to receive BNT162b2 at defined points as part of the study.

In order to describe the boostability of BNT162, and potential heterologous protection against emerging SARS-CoV-2 VOCs, an additional dose of BNT162b2 at 30 µg will be given to Phase 1 participants approximately 6 to 12 months after their second dose of BNT162b1 or BNT162b2. This will provide an early assessment of the safety of a third dose of BNT162, as well as its immunogenicity.

The assessment of boostability will be further expanded in a subset of Phase 3 participants at selected sites in the US who will receive a third dose of BNT162b2 at 30 µg or a third and potentially a fourth dose of prototype BNT162b2VOC at 30 µg (BNT162b2s01, based upon the South African variant and hereafter referred to as BNT162b2SA). A further subset of Phase 3 participants will receive a third, lower, dose of BNT162b2 at 5 or 10 µg.

To further describe potential homologous and heterologous protection against emerging SARS-CoV-2 VOCs, a new cohort of participants will be enrolled who are COVID-19 vaccine-naïve (ie, BNT162b2-naïve) and have not experienced COVID-19. They will receive BNT162b2SA given as a 2-dose series, separated by 21 days.

To reflect current and anticipated recommendations for COVID 19 vaccine boosters, participants in C4591001 who meet specified recommendations and have not already received one, will be offered a third dose of BNT162b2 after their second dose of BNT162.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2 Infection COVID-19	Biological: BNT162b1 Biological: BNT162b2 Other: Placebo Biological: BNT162b2SA	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

46949 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

A PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY INDIVIDUALS

Actual Study Start Date :

Apr 29, 2020

Anticipated Primary Completion Date :

Feb 8, 2024

Anticipated Study Completion Date :

Feb 8, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 10 µg dose, 18-55 years of age (2 doses)	Biological: BNT162b1 Intramuscular injection Biological: BNT162b2 Intramuscular injection
Experimental: 20 µg dose, 18-55 years of age (2 doses)	Biological: BNT162b1 Intramuscular injection Biological: BNT162b2 Intramuscular injection
Experimental: 30 µg dose, 18-55 years of age (2 doses)	Biological: BNT162b1 Intramuscular injection Biological: BNT162b2 Intramuscular injection
Experimental: 10 µg dose, 65-85 years of age (2 doses)	Biological: BNT162b1 Intramuscular injection Biological: BNT162b2 Intramuscular injection
Experimental: 20 µg dose, 65-85 years of age (2 doses)	Biological: BNT162b1 Intramuscular injection Biological: BNT162b2 Intramuscular injection
Experimental: 30 µg dose, 65-85 years of age (2 doses)	Biological: BNT162b1 Intramuscular injection Biological: BNT162b2 Intramuscular injection
Experimental: 30 µg dose, ≥12 years of age (2 doses)	Biological: BNT162b2 Intramuscular injection
Placebo Comparator: Placebo, 18-55 years of age	Other: Placebo Intramuscular injection
Placebo Comparator: Placebo, 65-85 years of age	Other: Placebo Intramuscular injection
Placebo Comparator: Placebo, ≥12 years of age	Other: Placebo Intramuscular injection
Experimental: 100 µg dose, 18-55 years of age (2 doses)	Biological: BNT162b1 Intramuscular injection
Other: Vaccination of Placebo recipients with BNT162b2 - Stage 1 Participants ≥16 years of age who originally received placebo and are eligible for COVID-19 vaccination following any local or national recommendations will be offered the opportunity to receive BNT162b2 as part of the study.	Biological: BNT162b2 Intramuscular injection
Other: Vaccination of placebo recipients with BNT162b2 - Stage 2 Participants ≥16 years of age who originally received placebo will be offered the opportunity to receive BNT162b2 at defined points as part of the study.	Biological: BNT162b2 Intramuscular injection
Experimental: Booster vaccination of Phase 1 participants with BNT162b2 at a dose of 30 µg	Biological: BNT162b2 Intramuscular injection
Experimental: Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 30 µg	Biological: BNT162b2 Intramuscular injection
Experimental: Booster vaccination of Phase 3 participants with BNT162b2SA at a dose of 30 µg	Biological: BNT162b2SA Intramuscular injection
Experimental: Vaccination of BNT162b2-naive participants with BNT162b2SA at a dose of 30 µg	Biological: BNT162b2SA Intramuscular injection
Experimental: Booster and further vaccination of Phase 3 participants with BNT162b2SA at a dose of 30 µg	Biological: BNT162b2SA Intramuscular injection
Experimental: Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 5 µg	Biological: BNT162b2 Intramuscular injection
Experimental: Booster vaccination of Phase 3 participants with BNT162b2 at a dose of 10 µg	Biological: BNT162b2 Intramuscular injection

Outcome Measures

Primary Outcome Measures

Percentage of participants in Phase 1 reporting local reactions [For 7 days after dose 1 and dose 2]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Percentage of participants in Phase 1 reporting systemic events [For 7 days after dose 1 and dose 2]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Percentage of participants in Phase 1 reporting adverse events [From dose 1 through 1 month after the last dose]
As elicited by investigational site staff
Percentage of participants in Phase 1 reporting serious adverse events [From dose 1 through 6 months after the last dose]
As elicited by investigational site staff
Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values [1 day after dose 1]
As measured at the central laboratory
Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values [7 days after dose 1]
As measured at the central laboratory
Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values [7 days after dose 2]
As measured at the central laboratory
Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments [Between baseline and 1 day after dose 1]
As measured at the central laboratory
Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments [Between baseline and 7 days after dose 1]
As measured at the central laboratory
Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments [Between before dose 2 and 7 days after dose 2]
As measured at the central laboratory
In the first 360 participants randomized into Phase 2/3, percentage of participants reporting local reactions [For 7 days after dose 1 and dose 2]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In the first 360 participants randomized into Phase 2/3, percentage of participants reporting systemic events [For 7 days after dose 1 and dose 2]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
In the first 360 participants randomized into Phase 2/3, percentage of participants reporting adverse events [From dose 1 through 1 month after the last dose]
As elicited by investigational site staff
In the first 360 participants randomized into Phase 2/3, percentage of participants reporting serious adverse events [From dose 1 through 6 months after the last dose]
As elicited by investigational site staff
In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting local reactions [For 7 days after dose 1 and dose 2]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting systemic events [For 7 days after dose 1 and dose 2]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Percentage of participants in Phase 2/3 reporting adverse events [From dose 1 through 1 month after the last dose]
As elicited by investigational site staff
Percentage of participants in Phase 2/3 reporting serious adverse events [From dose 1 through 6 months after the last dose]
As elicited by investigational site staff
Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [From 7 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [From 7 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Percentage of participants 12-15 years of age in Phase 3 reporting adverse events [From dose 1 through 1 month after the last dose]
As elicited by investigational site staff
Percentage of participants 12-15 years of age in Phase 3 reporting adverse events [From dose 1 through 6 months after the last dose]
As elicited by investigational site staff
In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting local reactions [For 7 days after dose 1 and dose 2]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting systemic events [For 7 days after dose 1 and dose 2]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
In participants who receive BNT162b2SA given as 1 or 2 doses, percentage of participants reporting adverse events [From dose 1 through 1 month after the last dose]
As elicited by investigational site staff
In participants who receive BNT162b2SA given as 1 or 2 doses, percentage of participants reporting serious adverse events [From dose 1 through 5 or 6 months after the last dose]
As elicited by investigational site staff
In participants, who receive BNT162b2SA given as 1 or 2 doses, percentage of participants reporting local reactions [For 7 days after dose 1 (and dose 2)]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In participants who receive BNT162b2SA given as 1 or 2 doses, percentage of participants reporting systemic events [For 7 days after dose 1 (and dose 2)]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
In participants who receive a third dose of BNT162b2 as part of the subset for evaluation of boostability and protection against emerging VOCs, percentage of participants reporting adverse events [From the third dose through 1 month after the third dose]
As elicited by investigational site staff
In participants who receive a third dose of BNT162b2 as part of the subset for evaluation of boostability and protection against emerging VOCs, percentage of participants reporting serious adverse events [From the third dose through 6 months after the third dose]
As elicited by investigational site staff
In participants who receive a third dose of BNT162b2 as part of the subset for evaluation of boostability and protection against emerging VOCs, percentage of participants reporting local reactions [For 7 days after the third dose]
Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
In participants who receive a third dose of BNT162b2 as part of the subset for evaluation of boostability and protection against emerging VOCs, percentage of participants reporting systemic events [For 7 days after the third dose]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
In participants who receive a third dose of BNT162b2 as a result of current or anticipated recommendations, percentage of participants reporting adverse events [From the third dose through 1 month after the third dose]
As elicited by investigational site staff
In participants who receive a third dose of BNT162b2 as a result of current or anticipated recommendations, percentage of participants reporting serious adverse events [From the third dose through 6 months after the third dose]
As elicited by investigational site staff
Noninferiority of the SARS-CoV-2 reference strain neutralizing titers after a third dose of BNT162b2 at 30 µg compared to after 2 doses of BNT162b2, in the same individuals [1 month after the third dose]
As measured at the central laboratory
Noninferiority of the SARS-CoV-2 SA strain neutralizing titers after one dose of BNT162b2SA compared to the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2, in the same individuals [1 month after the third dose]
As measured at the central laboratory
Noninferiority of the SARS-CoV-2 SA strain neutralizing titers after 2 doses of BNT162b2SA compared to the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2 [1 month after the second dose]
As measured at the central laboratory

Secondary Outcome Measures

In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs [Through 2 years after the final dose]
As measured at the central laboratory
In Phase 1 participants, GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point [Through 2 years after the final dose]
As measured at the central laboratory
Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels [Through 2 years after the final dose]
As measured at the central laboratory
In Phase 1 participants, SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels, expressed as GMCs [Through 2 years after the final dose]
As measured at the central laboratory
Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels [Through 2 years after the final dose]
As measured at the central laboratory
In Phase 1 participants, GMFR in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels from before vaccination to each subsequent time point [Through 2 years after the final dose]
As measured at the central laboratory
In Phase 1 participants, GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 (anti-S1 and anti-RBD) binding antibody levels [Through 2 years after the final dose]
As measured at the central laboratory
Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [From 14 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [From 14 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [From 7 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [From 14 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [From 7 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [From 14 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination [From 7 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination [From 14 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination [From 7 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination [From 14 days after the second dose of study intervention to the end of the study, up to 2 years]
Per 1000 person-years of follow-up
GMR of SARS CoV 2 neutralizing titers in the 2 age groups (12-15 years of age to 16-25 years of age) [1 month after the second dose]
As measured at the central laboratory
Incidence of asymptomatic SARS CoV-2 infection based on N binding antibody seroconversion in participants with no serological or virological evidence of past SARS CoV-2 infection or confirmed COVID-19 prior to 1 month after receipt of the second dose [Through 1 month after the second dose]
Per 1000 person-years of follow-up
Incidence of asymptomatic SARS CoV-2 infection based on central laboratory-confirmed NAAT in participants with no serological or virological evidence (up to the start of the asymptomatic surveillance period) of past SARS-CoV-2 infection [Through 6 months after the second dose]
Per 1000 person-years of follow-up
Noninferiority of the SARS-CoV-2 SA strain neutralizing titers after a third dose of BNT162b2 at 30 µg compared to the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2, in the same individuals [1 month after the third dose]
As measured at the central laboratory
Noninferiority of the SARS-CoV-2 reference strain neutralizing titers after one dose of BNT162b2SA compared to after 2 doses of BNT162b2, in the same individuals [1 month after the first dose of BNT162b2SA]
As measured at the central laboratory
Comparison of the SARS-CoV-2 SA strain neutralizing titers after 1 dose of BNT162b2SA to after a third dose of BNT162b2 at 30 µg [1 month after the first dose of BNT162b2SA/third dose of BNT162b2]
As measured at the central laboratory
Comparison of the SARS-CoV-2 SA strain neutralizing titers after 2 doses of BNT162b2SA to the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2, in the same individuals [1 month after the second dose of BNT162b2SA]
As measured at the central laboratory
Comparison of the SARS-CoV-2 SA strain neutralizing titers after 2 doses of BNT162b2SA to after 2 doses of BNT162b2 [1 month after the second dose]
As measured at the central laboratory
Comparison of the SARS-CoV-2 reference strain neutralizing titers after 2 doses of BNT162b2SA to after 2 doses of BNT162b2 [1 month after the second dose]
As measured at the central laboratory

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

• Male or female participants between the ages of 18 and 55 years, inclusive, 65 and 85 years, inclusive, or ≥12 years, inclusive, at randomization (dependent upon study phase). For the boostability and protection-against-VOCs subset: Existing participants enrolled to receive a third dose of BNT162b2 at 30 µg or BNT162b2SA; male or female participants between the ages of 18 and 55 years, inclusive, at rerandomization.

Newly enrolled participants enrolled to receive 2 doses of BNT162b2SA; male or female participants between the ages of 18 and 55 years, inclusive, at enrollment.

Existing participants enrolled to receive a third dose of BNT162b2 at 5 or 10 µg; male or female participants ≥18 years at rerandomization.

Note that participants <18 years of age cannot be enrolled in the EU.

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, and clinical judgment of the investigator to be eligible for inclusion in the study.
Participants who, in the judgment of the investigator, are at risk for acquiring COVID-19.
Boostability and protection-against-VOCs existing participant subset only: Participants who provided a serum sample at Visit 3, with Visit 3 occurring within the protocol-specified window.
Capable of giving personal signed informed consent

Exclusion Criteria:

Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
Phases 1 and 2 only: Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
Receipt of medications intended to prevent COVID 19.
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
Phase 1 only: Individuals at high risk for severe COVID-19, including those with any of the following risk factors:
Hypertension
Diabetes mellitus
Chronic pulmonary disease
Asthma
Current vaping or smoking
History of chronic smoking within the prior year
BMI >30 kg/m2
Anticipating the need for immunosuppressive treatment within the next 6 months
Phase 1 only: Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
Phase 1 only: Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention.
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.
Previous vaccination with any coronavirus vaccine.
Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
Participation in other studies involving study intervention within 28 days prior to study entry through and including 6 months 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.
Previous participation in other studies involving study intervention containing lipid nanoparticles.
Phase 1 only: Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the screening visit.
Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality.
Phase 1 only: Positive test for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBc Abs), or hepatitis C virus antibodies (HCV Abs) at the screening visit.
Phase 1 only: SARS-CoV-2 NAAT-positive nasal swab within 24 hours before receipt of study intervention.
Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Alabama Research Center, LLC	Athens	Alabama	United States	35611
2	Birmingham Clinical Research Unit	Birmingham	Alabama	United States	35216
3	Medical Affiliated Research Center	Huntsville	Alabama	United States	35801
4	Optimal Research, LLC	Huntsville	Alabama	United States	35802
5	Alliance for Multispecialty Research, LLC	Mobile	Alabama	United States	36608
6	Chinle Comprehensive Health Care Facility	Chinle	Arizona	United States	86503
7	Johns Hopkins Center for American Indian Health	Chinle	Arizona	United States	86503
8	The Pain Center of Arizona	Phoenix	Arizona	United States	85018
9	HOPE Research Institute	Phoenix	Arizona	United States	85023
10	Alliance for Multispecialty Research, LLC	Tempe	Arizona	United States	85281
11	Whiteriver Indian Hospital	Whiteriver	Arizona	United States	85941
12	Anaheim Clinical Trials, LLC	Anaheim	California	United States	92801
13	Collaborative Neuroscience Research, LLC	Long Beach	California	United States	90806
14	Long Beach Clinical Trials Services Inc.	Long Beach	California	United States	90806
15	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
16	National Research Institute	Los Angeles	California	United States	90057
17	Velocity Clinical Research, North Hollywood	North Hollywood	California	United States	91606
18	Paradigm Clinical Research Center	Redding	California	United States	96001
19	Kaiser Permanente Sacramento	Sacramento	California	United States	95815
20	Clinical and Translational Science Center (CTSC) Clinical Research Center (CCRC)	Sacramento	California	United States	95817
21	UC Davis Medical Center	Sacramento	California	United States	95817
22	California Research Foundation	San Diego	California	United States	92123-1881
23	Kaiser Permanente Santa Clara	Santa Clara	California	United States	95051
24	Bayview Research Group	Valley Village	California	United States	91607
25	Diablo Clinical Research, Inc.	Walnut Creek	California	United States	94598
26	Lynn Institute of Denver	Aurora	Colorado	United States	80012
27	Clinical Research Consulting, LLC	Milford	Connecticut	United States	06460
28	Yale Center for Clinical Investigations (CSRU)	New Haven	Connecticut	United States	06519
29	Alliance for Multispecialty Research	Coral Gables	Florida	United States	33134
30	DeLand Clinical Research Unit	DeLand	Florida	United States	32720
31	Fleming Island Center for Clinical Research	Fleming Island	Florida	United States	32003
32	Indago Research & Health Center, Inc	Hialeah	Florida	United States	33012
33	Research Centers of America	Hollywood	Florida	United States	33024
34	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
35	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	United States	32256
36	Acevedo Clinical Research Associates	Miami	Florida	United States	33142
37	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Orlando	Florida	United States	32801
38	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
39	IACT Health	Columbus	Georgia	United States	31904
40	Meridian Clinical Research, LLC	Savannah	Georgia	United States	31406
41	Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
42	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
43	Solaris Clinical Research	Meridian	Idaho	United States	83646
44	Optimal Research	Peoria	Illinois	United States	61614
45	University of Iowa Hospitals & Clinics Investigational Drug Servces	Iowa City	Iowa	United States	42242
46	University of Iowa Hospitals & Clinics	Iowa City	Iowa	United States	52242
47	Meridian Clinical Research, LLC	Sioux City	Iowa	United States	51106
48	Alliance for Multispecialty Research, LLC	Newton	Kansas	United States	67114
49	Alliance for Multispecialty Research, LLC	Wichita	Kansas	United States	67207
50	Kentucky Pediatric/ Adult Research	Bardstown	Kentucky	United States	40004
51	Benchmark Research	Metairie	Louisiana	United States	70006
52	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
53	LSU Health Sciences Center at Shreveport Clinical Trials Office	Shreveport	Louisiana	United States	71101
54	LSUHSC-Shreveport	Shreveport	Louisiana	United States	71103
55	Pharmaron CPC, Inc.	Baltimore	Maryland	United States	21201
56	University of Maryland Medical Center Investigational Drug Service Pharmacy	Baltimore	Maryland	United States	21201
57	University of Maryland, Baltimore, Health Sciences Research Facility III	Baltimore	Maryland	United States	21201
58	University of Maryland, Center for Vaccine Development and Global Health	Baltimore	Maryland	United States	21201
59	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224
60	Boston Medical Center	Boston	Massachusetts	United States	02118
61	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts	United States	01655
62	Michigan Center for Medical Research	Farmington Hills	Michigan	United States	48334
63	MedPharmics, LLC	Gulfport	Mississippi	United States	39503
64	Clinical Research Professionals	Chesterfield	Missouri	United States	63005
65	Sundance Clinical Research, LLC	Saint Louis	Missouri	United States	63141
66	Bozeman Health Deaconess Hospital dba Bozeman Health Clinical Research	Bozeman	Montana	United States	59715
67	Bozeman Health Deaconess Hospital	Bozeman	Montana	United States	59715
68	Methodist Physicians Clinic / CCT Research	Fremont	Nebraska	United States	68025
69	Meridian Clinical Research, LLC	Norfolk	Nebraska	United States	68701
70	Quality Clinical Research, Inc.	Omaha	Nebraska	United States	68114
71	Meridian Clinical Research, LLC	Omaha	Nebraska	United States	68134
72	Wake Research-Clinical Research Center of Nevada, LLC	Las Vegas	Nevada	United States	89106
73	Amici Clinical Research	Raritan	New Jersey	United States	08869
74	South Jersey Infectious Disease	Somers Point	New Jersey	United States	08244
75	Johns Hopkins Center for American Indian Health	Gallup	New Mexico	United States	87301
76	Johns Hopkins Center for American Indian Health	Shiprock	New Mexico	United States	87420
77	Meridian Clinical Research, LLC	Binghamton	New York	United States	13901
78	Meridian Clinical Research LLC	Endwell	New York	United States	13760
79	NYU Langone Health	New York	New York	United States	10016
80	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
81	Rochester Clinical Research, Inc.	Rochester	New York	United States	14609
82	University of Rochester Medical Center	Rochester	New York	United States	14642
83	SUNY Upstate Medical University Global Health Research Unit	Syracuse	New York	United States	13215
84	PMG Research of Raleigh, LLC d/b/a PMG Research of Cary	Cary	North Carolina	United States	27518
85	PMG Research of Charlotte LLC	Charlotte	North Carolina	United States	28209
86	Accessioning Unit and Repository	Durham	North Carolina	United States	27703
87	Duke Vaccine and Trials Unit	Durham	North Carolina	United States	27703
88	Clinical Research Pickett Road	Durham	North Carolina	United States	27705
89	Duke Investigational Drug Service Pharmacy	Durham	North Carolina	United States	27710
90	PharmQuest	Greensboro	North Carolina	United States	27408
91	PMG Research of Hickory, LLC	Hickory	North Carolina	United States	28601
92	PMG Research of Raleigh, LLC	Raleigh	North Carolina	United States	27609
93	M3 Wake Research, Inc.	Raleigh	North Carolina	United States	27612
94	PMG Research of Salisbury, LLC	Salisbury	North Carolina	United States	28144
95	PMG Research of Wilmington, LLC	Wilmington	North Carolina	United States	28401
96	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina	United States	27103
97	Lillestol Research Llc	Fargo	North Dakota	United States	58104
98	Meridian Clinical Research, LLC	Cincinnati	Ohio	United States	45219
99	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
100	Meridian Clinical Research LLC	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, Inc.	Cleveland	Ohio	United States	44122
104	Aventiv Research Inc.	Columbus	Ohio	United States	43213
105	Dayton Clinical Research	Dayton	Ohio	United States	45406
106	Dayton Clinical Research	Dayton	Ohio	United States	45409
107	PriMED Clinical Research	Dayton	Ohio	United States	45419
108	Senders Pediatrics	South Euclid	Ohio	United States	44121
109	Lynn Institute of Norman	Norman	Oklahoma	United States	73072
110	Kaiser Permanente Northwest-Center for Health Research	Portland	Oregon	United States	97227
111	Lehigh Valley Health Network/Network Office of Research and Innovation	Allentown	Pennsylvania	United States	18102
112	Velocity Clinical Research, Providence	East Greenwich	Rhode Island	United States	02818
113	Main Street Physician's Care	Little River	South Carolina	United States	29566
114	Main Street Physician's Care	Loris	South Carolina	United States	29569
115	Holston Medical Group	Bristol	Tennessee	United States	37620
116	Holston Medical Group	Kingsport	Tennessee	United States	37660
117	Alliance for Multispecialty Research, LLC	Knoxville	Tennessee	United States	37909
118	Alliance for Multispecialty Research, LLC	Knoxville	Tennessee	United States	37920
119	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee	United States	38119
120	Clinical Research Associates, Inc.	Nashville	Tennessee	United States	37203
121	Trinity Clinical Research	Tullahoma	Tennessee	United States	37388
122	Benchmark Research	Austin	Texas	United States	78705
123	ARC Clinical Research at Wilson Parke	Austin	Texas	United States	78726
124	Tekton Research, Inc.	Austin	Texas	United States	78745
125	North Texas Infectious Diseases Consultants, P.A.	Dallas	Texas	United States	75246
126	Ventavia Research Group, LLC	Fort Worth	Texas	United States	76104
127	Benchmark Research	Fort Worth	Texas	United States	76135
128	Texas Health Resources	Fort Worth	Texas	United States	76135
129	University of Texas Medical Branch	Galveston	Texas	United States	77555
130	Ventavia Research Group, LLC	Houston	Texas	United States	77008
131	Texas Center for Drug Development, Inc.	Houston	Texas	United States	77081
132	Ventavia Research Group, LLC	Keller	Texas	United States	76248
133	SMS Clinical Research, LLC	Mesquite	Texas	United States	75149
134	LinQ Research, LLC	Pearland	Texas	United States	77584
135	Benchmark Research.	San Angelo	Texas	United States	76904
136	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
137	Diagnostics Research Group	San Antonio	Texas	United States	78229
138	Martin Diagnostic Clinic	Tomball	Texas	United States	77375
139	J. Lewis Research, Inc. / Foothill Family Clinic	Salt Lake City	Utah	United States	84109
140	J. Lewis Research, Inc. / Foothill Family Clinic South	Salt Lake City	Utah	United States	84121
141	Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)	Annandale	Virginia	United States	22003
142	Virginia Research Center LLC	Midlothian	Virginia	United States	23114
143	Benaroya Research Institute at Virginia Mason	Seattle	Washington	United States	98101
144	Wenatchee Valley Hospital	Wenatchee	Washington	United States	98801
145	Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich	Caba		Argentina	1426
146	Hospital Santo Antonio/ Associacao Obras Sociais Irma Dulce	Salvador	Bahia	Brazil	CEP: 40415-006
147	CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos Ltda (Casa Branca)	Sao Paulo		Brazil	04266-010
148	CRS Clinical Research Services Berlin GmbH	Berlin		Germany	13353
149	Medizentrum Essen Borbeck	Essen		Germany	45355
150	IKF Pneumologie GmbH & Co KG	Frankfurt am Main		Germany	60596
151	Universitätsklinikum Hamburg-Eppendorf	Hamburg		Germany	20359
152	CRS Clinical Research Services Mannheim GmbH	Mannheim		Germany	68167
153	Studienzentrum Brinkum Dr. Lars Pohlmeier und Torsten Drescher	Stuhr		Germany	28816
154	Newtown Clinical Research Centre	Johannesburg	Gauteng	South Africa	2113
155	Jongaie Research	Pretoria	Gauteng	South Africa	0183
156	Limpopo Clinical Research Initiative	Thabazimbi	Limpopo	South Africa	0380
157	Tiervlei Trial Centre, Basement Level, Karl Bremer Hospital	Cape Town	Western CAPE	South Africa	7530
158	Ankara Universitesi Tip Fakultesi, Ibni Sina Hastanesi	Ankara		Turkey	06230
159	Hacettepe Universitesi Tip Fakultesi	Ankara		Turkey	06230
160	Istanbul Yedikule Gogus Hastaliklari ve Gogus Cerrahisi Egitim Arastirma Hastanesi	Istanbul		Turkey	34020
161	Istanbul Universitesi Istanbul Tip Fakultesi	Istanbul		Turkey	34093
162	Istanbul Universitesi-Cerrahpasa, Cerrahpasa Tip Fakultesi	Istanbul		Turkey	34098
163	Medipol Mega Universite Hastanesi	Istanbul		Turkey	34214
164	Acibadem Atakent Hastanesi	Istanbul		Turkey	34303
165	Kocaeli Universitesi Tip Fakultesi	Kocaeli		Turkey	41380
166	Sakarya Universitesi Egitim ve Arastirma Hastanesi	Sakarya		Turkey	54100