A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Modified RNA Vaccine Against Influenza

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05052697

Collaborator

(none)

1,980

Enrollment

Locations

Arms

18.9

Anticipated Duration (Months)

20.2

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will be divided into two substudies - Substudy A (SSA) and Substudy B (SSB)

Substudy A This is a Phase 1 randomized substudy to evaluate the safety and immunogenicity of monovalent influenza modRNA vaccine (mIRV) and bivalent influenza modRNA vaccine (bIRV) at various dose levels, and quadrivalent influenza modRNA vaccine (qIRV), in participants 65 to 85 years of age. Participants will receive at Vaccination 1 either:

1 of 4 dose levels of mIRV (either A or B Strain),
1 of 4 dose levels of bIRV (containing both A and B strains),
qIRV (at 1 dose level), or
A licensed quadrivalent influenza vaccine (QIV).

At approximately 8 weeks following Vaccination 1, participants will be unblinded and QIV (Vaccination 2) administered to participants not having previously received this at Vaccination 1. Additionally, participants who previously received QIV at Vaccination 1 will receive one of the following for Vaccination 2:

mIRV encoding A strain at dose level 4, or
mIRV encoding B strain at dose level 4.

Substudy B

This is a randomized substudy to evaluate the safety and immunogenicity of the following vaccination schedules in participants 65 to 85 years of age:

2-Visit Schedules

2 doses of qIRV (at a dose level 1), administered 21 days apart.
2 doses of licensed QIV, administered 21 days apart (as a control group)
A dose of licensed QIV following by a dose of bIRV encoding 2 A strains at dose level combination 1 or 2, administered 21 days apart.

1-Visit Schedules

A dose of licensed QIV administered concurrently in the opposite arm with bIRV encoding 2 A strains at dose level combination 1 or 2.
A dose of bIRV encoding 2 A strains administered concurrently in the opposite arm with a dose of bIRV encoding 2 B strains.at dose level 1.
A dose of qIRV encoding 2 A strains and 2 B strains at dose level 2 (at one of two possible dose level combinations).
A dose of qIRV encoding 2 A strains and 2 B strains at dose level 3.
1 dose of licensed QIV (as a control group).

Substudy B

In participants 18 to 64 years of age:

-A dose of qIRV encoding 2 A strains and 2 B strains at a dose level combination 1 or 2.

Condition or Disease	Intervention/Treatment	Phase
Influenza, Human	Biological: mIRV Biological: bIRV AB Biological: qIRV Biological: QIV Biological: bIRV AA Biological: bIRV BB	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1980 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

SSA: observer-blinded, sponsor unblind SSB: single-blind, sponsor unblind

Primary Purpose:

Prevention

Official Title:

A PHASE 1/2 RANDOMIZED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST INFLUENZA IN HEALTHY INDIVIDUALS

Actual Study Start Date :

Sep 13, 2021

Anticipated Primary Completion Date :

Apr 12, 2023

Anticipated Study Completion Date :

Apr 12, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SSA: mIRV A (dose level 1) + QIV	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: mIRV A (dose level 2) + QIV	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: mIRV A (dose level 3) + QIV	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: mIRV A (dose level 4) + QIV	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: mIRV B (dose level 1) + QIV	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: mIRV B (dose level 2) + QIV	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: mIRV B (dose level 3) + QIV	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: mIRV B (dose level 4) + QIV	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: bIRV AB (dose level combination 1) + QIV	Biological: bIRV AB Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: bIRV AB (dose level combination 2) + QIV	Biological: bIRV AB Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: bIRV AB (dose level combination 3) + QIV	Biological: bIRV AB Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: bIRV AB (dose level combination 4) + QIV	Biological: bIRV AB Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: QIV + mIRV A strain (dose level 4)	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: qIRV (dose level 1) + QIV	Biological: qIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSA: QIV + mIRV B strain (dose level 4)	Biological: mIRV Intramuscular injection Biological: QIV Intramuscular injection
Experimental: SSB: 2 doses of qIRV (dose level 1), 2-visit schedule	Biological: qIRV Intramuscular injection
Experimental: SSB: 2 doses of QIV, 2-visit schedule	Biological: QIV Intramuscular injection
Experimental: SSB: QIV + bIRV AA (dose level combination 1), 2-visit schedule	Biological: QIV Intramuscular injection Biological: bIRV AA Intramuscular injection
Experimental: SSB: QIV + bIRV AA (dose level combination 2), 2-visit schedule	Biological: QIV Intramuscular injection Biological: bIRV AA Intramuscular injection
Experimental: SSB: QIV + bIRV AA (dose level combination 1), 1-visit schedule	Biological: QIV Intramuscular injection Biological: bIRV AA Intramuscular injection
Experimental: SSB: QIV + bIRV AA (dose level combination 2), 1-visit schedule	Biological: QIV Intramuscular injection Biological: bIRV AA Intramuscular injection
Experimental: SSB: qIRV (dose level 2, dose combination 1), 1-visit schedule NOTE: Arm Description has not been entered.	Biological: qIRV Intramuscular injection
Experimental: SSB: qIRV (dose level 2, dose combination 2), 1-visit schedule NOTE: Arm Description has not been entered	Biological: qIRV Intramuscular injection
Experimental: SSB: qIRV (dose level 3), 1-visit schedule NOTE: Arm Description has not been entered	Biological: qIRV Intramuscular injection
Experimental: SSB: bIRV AA + bIRV BB (both dose level combination 1), 1-visit schedule NOTE: Arm Description has not been entered	Biological: bIRV AA Intramuscular injection Biological: bIRV BB Intramuscular injection
Experimental: SSB: 1 dose of QIV, 1-visit schedule NOTE: Arm Description has not been entered	Biological: QIV Intramuscular injection
Experimental: SSB: qIRV (dose level 1), 1-visit schedule NOTE: Arm Description has not been entered.	Biological: qIRV Intramuscular injection
Experimental: SSB: qIRV (dose level 2), 1-visit schedule NOTE: Arm Description has not been entered.	Biological: qIRV Intramuscular injection

Outcome Measures

Primary Outcome Measures

SSA: Percentage of participants reporting local reactions [For 7 days after Vaccinations 1 and 2]
Pain at the injection site, redness, and swelling, as self-reported in electronic diaries.
SSA: Percentage of participants reporting systemic events [For 7 days after Vaccinations 1 and 2]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self reported in electronic diaries.
SSA: Percentage of participants reporting adverse events [From vaccination to 4 weeks after Vaccinations 1 and 2]
As elicited by investigational site staff.
SSA: Percentage of participants reporting serious adverse events [From vaccination to 6 months after the last study vaccination]
As elicited by investigational site staff.
SSA: Percentage of participants with abnormal hematology and chemistry laboratory values [2 days after Vaccination 1]
As measured at the central laboratory
SSA: Percentage of participants with abnormal hematology and chemistry laboratory values [1 week after Vaccination 1]
As measured at the central laboratory
SSA: Percentage of participants with grading shifts in hematology and chemistry laboratory assessments [Between baseline and 2 days after Vaccination 1]
As measured at the central laboratory
SSA: Percentage of participants with grading shifts in hematology and chemistry laboratory assessments [Between baseline and 1 week after Vaccination 1]
As measured at the central laboratory
SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities [2 days after Vaccination 1]
ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist
SSA: Percentage of participants with new ECG abnormalities [1 week after Vaccination 1]
ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist
SSB: Percentage of participants reporting local reactions (18 to 64 and 65 to 85 years of age) [For 7 days after each vaccination]
Pain at the injection site, redness, and swelling, as self-reported in electronic diaries.
SSB: Percentage of participants reporting systemic events (18 to 64 and 65 to 85 years of age) [For 7 days after each vaccination]
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self reported in electronic diaries.
SSB: Percentage of participants reporting adverse events (18 to 64 and 65 to 85 years of age) [From Vaccination 1 to 4 weeks after the last vaccination]
As elicited by investigational site staff.
SSB: Percentage of participants reporting serious adverse events (18 to 64 and 65 to 85 years of age) [From Vaccination 1 to 6 months after the last vaccination]
As elicited by investigational site staff.
SSB: Percentage of participants with abnormal troponin I laboratory values (18 to 64 and 65 to 85 years of age) [2 days after the last vaccination]
As measured at the central laboratory
SSB: Percentage of participants with new ECG abnormalities (18 to 64 and 65 to 85 years of age) [2 days after the last vaccination]
ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist

Secondary Outcome Measures

SSA: Geometric mean titers (GMTs) of hemagglutination inhibition (HAI) titers [At Baseline, and 1-, 4- and 8-weeks after Vaccination 1]
As measured at the central laboratory
SSA: Geometric mean fold rise (GMFR) in HAI titers from before vaccination to each subsequent timepoint [At 1-, 4-, and 8-weeks after Vaccination 1]
As measured at the central laboratory
SSA: Proportion of participants achieving HAI seroconversion for each strain [At 1-, 4-, and 8-weeks after Vaccination 1]
As measured at the central laboratory
SSA: Proportion of participants with HAI titer >=1:40 for each strain [At Baseline, and 1-, 4-, and 8-weeks after Vaccination 1]
As measured at the central laboratory.
SSA: In participants who receive either qIRV or QIV at Vaccination 1, the proportion of participants achieving HAI seroconversion for all strains [At 1-, 4-, and 8-weeks after Vaccination 1]
As measured at the central laboratory
SSA: In participants who receive either qIRV or QIV at Vaccination 1, the proportion of participants with HAI titer >=1:40 for all strains [At Baseline, and 1-, 4-, and 8-weeks after Vaccination 1]
As measured at the central laboratory.
SSA: The geometric mean ratio (GMR) of the geometric mean of HAI titers from participants receiving qIRV to the geometric mean of HAI titers from participants receiving QIV [At 4 weeks after Vaccination 1]
As measured at the central laboratory
SSA: The difference in percentage of participants achieving HAI seroconversion for each strain in qIRV recipients compared to licensed QIV recipients [At 4 week after Vaccination 1]
As measured at the central laboratory
SSB: GMTs of HAI titers (65-85 years of age) [At Baseline, prior to Vaccination 2 (if applicable), and 1-, 4- and 8-weeks after the last vaccination]
As measured at the central laboratory
SSB: GMFR in HAI titers from before vaccination to each subsequent timepoint (65-85 years of age) [Prior to Vaccination 2 (if applicable), and at 1-, 4-, and 8-weeks after the last vaccination]
As measured at the central laboratory
SSB: Proportion of participants achieving HAI seroconversion for each strain (65-85 years of age) [Prior to Vaccination 2 (if applicable), and at 1-, 4-, and 8-weeks after the last vaccination]
As measured at the central laboratory
SSB: Proportion of participants with HAI titer >=1:40 for each strain (65-85 years of age) [At Baseline, prior to Vaccination 2 (if applicable), and 1-, 4-, and 8-weeks after the last vaccination]
As measured at the central laboratory.
SSB: In participants who receive either qIRV or QIV, the proportion of participants achieving HAI seroconversion for all strains (65-85 years of age) [Prior to Vaccination 2 (if applicable), and at 1-, 4-, and 8-weeks after the last vaccination]
As measured at the central laboratory
SSB: In participants who receive either qIRV or QIV at Vaccination 1, the proportion of participants with HAI titer >=1:40 for all strains (65-85 years of age) [At Baseline, prior to Vaccination 2 (if applicable), and 1-, 4-, and 8-weeks after the last vaccination]
As measured at the central laboratory.
SSB: GMTs of HAI titers (18-64 years of age) [At Baseline, prior to Vaccination and 1-, 4- and 8-weeks after vaccination]
As measured at the central laboratory
SSB: GMFR in HAI titers from before vaccination to each subsequent timepoint (18-64years of age) [Prior to Vaccination, and at 1-, 4-, and 8-weeks after vaccination]
As measured at the central laboratory
SSB: Proportion of participants achieving HAI seroconversion for each strain (18-64 years of age) [Prior to Vaccination, and at 1-, 4-, and 8-weeks after vaccination]
As measured at the central laboratory
SSB: Proportion of participants with HAI titer >=1:40 for each strain (18-64 years of age) [At Baseline, prior to Vaccination, and 1-, 4-, and 8-weeks after vaccination]
As measured at the central laboratory.
SSB: In participants who receive either qIRV or QIV, the proportion of participants achieving HAI seroconversion for all strains (18-64 years of age) [Prior to Vaccination, and at 1-, 4-, and 8-weeks after vaccination]
As measured at the central laboratory
SSB: In participants who receive either qIRV or QIV at Vaccination 1, the proportion of participants with HAI titer >=1:40 for all strains (18-64 years of age) [At Baseline, prior to Vaccination, and 1-, 4-, and 8-weeks after vaccination]
As measured at the central laboratory.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Substudy A

Inclusion Criteria:

Male or female participants 65 to 85 years of age.
Participants who are willing and able to comply with all scheduled visits, treatment 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.
Male participant who is able to father children and willing to use an acceptable method of contraception; or female participant not of childbearing potential; or male participant not able to father children.
Capable of giving signed informed consent.

Exclusion Criteria:

Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
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.
Allergy to egg proteins (egg or egg products) or chicken proteins.
Participant who has had significant exposure to laboratory-confirmed SARS-CoV-2 infection, COVID-19, or influenza in the past 14 days known prior to Visit 1
Any participant who has a SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to Visit 1 that has not been confirmed as negative.
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 planned receipt throughout the study.
Vaccination with any influenza vaccine within 6 months (175 days) before study intervention administration.
Any participant who has received or plans to receive a modRNA-platform SARS-CoV-2 vaccine within 60 days of Visit 1
Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
Screening hematology/blood chemistry lab >=Grade 1 abnormality. Except Bilirubin, other stable Grade1 abnormalities may be considered eligible by Investigator.
Screening ECG that is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or study results.
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.
Participation in strenuous or endurance exercise through Visit 3.
Prior history of heart disease.

Substudy B

Inclusion Criteria:

Male or female participants 65 to 85 years of age or .Male or female participants 18 to 64 years of age
Participants who are willing and able to comply with all scheduled visits, treatment 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.
For participants 65 to 85 years of age at the time of enrollment, receipt of licensed influenza vaccination for the 2021-2022 northern hemisphere season >4 months (120 days) before study intervention administration.
Capable of giving signed informed consent.

Exclusion Criteria:

Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
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.
Allergy to egg proteins (egg or egg products) or chicken proteins.
Participant who has had significant exposure to laboratory-confirmed SARS-CoV-2 infection, COVID-19, or influenza in the past 14 days known prior to Visit 201
Any participant who has a SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to Visit 201 that has not been confirmed as negative.
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 planned receipt throughout the study.
Any participant who has received or plans to receive a modRNA-platform SARS-CoV-2 vaccine within 28 days of Visit 201
Any participant who has received licensed influenza vaccination for the 2022-2023 northern hemisphere influenza season.
Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
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.
Participation in strenuous or endurance exercise through Visit 205.
Prior history of heart disease.
Any abnormal screening troponin I laboratory value
Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Alabama Research Center	Athens	Alabama	United States	35611
2	The Heart Center	Athens	Alabama	United States	35611
3	Arizona Heart Rhythm Center	Phoenix	Arizona	United States	85016
4	Hope Research Institute	Phoenix	Arizona	United States	85018
5	The Pain Center of Arizona	Phoenix	Arizona	United States	85018
6	Noble Clinical Research	Tucson	Arizona	United States	85704
7	Pima Heart and Vascular	Tucson	Arizona	United States	85704
8	Inland Valley Cardiovascular Center	Murrieta	California	United States	92563
9	Orange County Heart Institute	Orange	California	United States	92868
10	Artemis Institute for Clinical Research	Riverside	California	United States	92503
11	Orange County Research Center	Tustin	California	United States	92780
12	Pediatrics-Infectious Diseases - Clinical Trials Center at University of Colorado Anschutz Medical C	Aurora	Colorado	United States	80045
13	UCHealth Heart and Vascular Center - Anschutz Medical Campus	Aurora	Colorado	United States	80045
14	Yale University School of Medicine	New Haven	Connecticut	United States	06510
15	Yale Cardiology	New Haven	Connecticut	United States	06519
16	Yale University School of Medicine	New Haven	Connecticut	United States	06519
17	Alliance for Multispecialty Research, LLC	Coral Gables	Florida	United States	33134
18	Halifax Health Medical Center	Daytona Beach	Florida	United States	32114
19	NYU Langone Cardiology Associates	Delray Beach	Florida	United States	33484
20	First Coast Heart & Vascular Center	Fleming Island	Florida	United States	32003
21	Fleming Island Center for Clinical Research	Fleming Island	Florida	United States	32003
22	Invesclinic	Fort Lauderdale	Florida	United States	33308
23	Alliance for Multispecialty Research, LLC	Fort Myers	Florida	United States	33912
24	Millennium Physician Group	Fort Myers	Florida	United States	33912
25	Robert B. Pritt, DO	Fort Myers	Florida	United States	33912
26	Direct Helpers Research Center.	Hialeah	Florida	United States	33012
27	Best Quality Research,Inc.	Hialeah	Florida	United States	33016
28	Elixia Infectious Disease, LLC	Hollywood	Florida	United States	33024
29	First Coast Heart & Vascular Center	Jacksonville	Florida	United States	32216
30	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Jacksonville	Florida	United States	32256
31	Premier Cardiology and Vascular Associates	Maitland	Florida	United States	32751
32	LMG Research	Miami	Florida	United States	33125
33	Millennium Clinical Research	Miami	Florida	United States	33125
34	Optimus U Corporation	Miami	Florida	United States	33125
35	Suncoast Research Group	Miami	Florida	United States	33135
36	Schiff Center for Liver Diseases/University of Miami	Miami	Florida	United States	33136
37	University of Miami Hospital	Miami	Florida	United States	33136
38	Dr Gerardo A. Polanco, MD	Miami	Florida	United States	33156
39	Research Institute of South Florida	Miami	Florida	United States	33173
40	Entrust Clinical Research	Miami	Florida	United States	33176
41	Jackson Medical Group Cardiac Care	Miami	Florida	United States	33176
42	Miami Dade Medical Research Institute, LLC	Miami	Florida	United States	33176
43	Clinical Neuroscience Solutions	Orlando	Florida	United States	32801
44	Central Florida Cardiology Group	Orlando	Florida	United States	32803
45	Innovation Medical Research Center	Palmetto Bay	Florida	United States	33157
46	DBC Research USA	Pembroke Pines	Florida	United States	33029
47	Progressive Medical Research	Port Orange	Florida	United States	32127
48	My Cardiologist	South Miami	Florida	United States	33143
49	Precision Clinical Research	Sunrise	Florida	United States	33351
50	Genesis Clinical Research	Tampa	Florida	United States	33603
51	Conquest Research	Winter Park	Florida	United States	32789
52	IACT Health	Columbus	Georgia	United States	31904
53	IACT Health	Rincon	Georgia	United States	31326
54	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
55	University of Iowa	Iowa City	Iowa	United States	52242
56	Alliance for Multispecialty Research, LLC	Wichita	Kansas	United States	67205
57	Alliance for Multispecialty Research, LLC	Wichita	Kansas	United States	67207
58	Heartland Cardiology, LLC	Wichita	Kansas	United States	67226
59	Centennial Medical Group	Elkridge	Maryland	United States	21075
60	Associates of Cardiology	Silver Spring	Maryland	United States	20910
61	Henry Ford Hospital	Detroit	Michigan	United States	48202
62	Pioneer Heart Institute	Lincoln	Nebraska	United States	68506
63	Meridian Clinical Research, LLC	Norfolk	Nebraska	United States	68701
64	Meridian Clinical Research - 3345 North 107th Street	Omaha	Nebraska	United States	68134
65	Meridian Clinical Research, LLC	Omaha	Nebraska	United States	68134
66	Sanjay Vohra, MD, F.A.C.C.	Henderson	Nevada	United States	89074
67	Wr-Crcn, Llc.	Las Vegas	Nevada	United States	89106
68	Excel Clinical Research, LLC	Las Vegas	Nevada	United States	89109
69	Las Vegas Clinical Trials	North Las Vegas	Nevada	United States	89030
70	Hassman Research Institute	Berlin	New Jersey	United States	08009
71	Penn Medicine	Somers Point	New Jersey	United States	08244
72	South Jersey Infectious Disease	Somers Point	New Jersey	United States	08244
73	NYU Langone - Center for the Prevention of Cardiovascular Disease	New York	New York	United States	10016
74	NYU Langone Health	New York	New York	United States	10016
75	Rochester General Hospital Infectious Disease	Rochester	New York	United States	14621
76	Rochester General Hospital	Rochester	New York	United States	14621
77	University of Rochester Medical Center	Rochester	New York	United States	14642
78	Upstate Health Care Center-University Cardiovascular Group of Syracuse	Syracuse	New York	United States	13202
79	SUNY Upstate Medical University Global Health Research Unit	Syracuse	New York	United States	13215
80	M3-Emerging Medical Research, LLC	Durham	North Carolina	United States	27704
81	Carolina Institute for Clinical Research	Fayetteville	North Carolina	United States	28303
82	Monroe Biomedical Research	Monroe	North Carolina	United States	28112
83	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
84	Aventiv Research Inc.	Columbus	Ohio	United States	43213
85	Aventiv Research Inc	Columbus	Ohio	United States	43213
86	Columbus Cardiovascular Associates, Inc	Columbus	Ohio	United States	43213
87	Pennsylvania Heart and Vascular Group	Jenkintown	Pennsylvania	United States	19046
88	Main Street Physician's Care	Little River	South Carolina	United States	29566
89	Prolato Clinical Research Center	Houston	Texas	United States	77054
90	DM Clinical Research	Houston	Texas	United States	77065
91	DM Clinical Research	Humble	Texas	United States	77338
92	Cedar Health Research	Irving	Texas	United States	75062
93	MacArthur Medical Center	Irving	Texas	United States	75062
94	Harmony Heart Group	Plano	Texas	United States	75093
95	Mt Olympus Medical Research	Sugar Land	Texas	United States	77479
96	DM Clinical Research	Tomball	Texas	United States	77375
97	Northwest Heart Center	Tomball	Texas	United States	77375
98	David Ramstad MD & Associates	Suffolk	Virginia	United States	23435