A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19

• Sponsor: ModernaTX, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04470427
• Collaborator: Biomedical Advanced Research and Development Authority (U.S. Fed), National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 30,000
• Locations: 100
• Arms: 2
• Anticipated Duration (Months): 29.1
• Patients Per Site: 300
• Patients Per Site Per Month: 10.3

Study Details

Study Description

Brief Summary

The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2 years after the second dose of mRNA-1273.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2	Biological: mRNA-1273; Biological: Placebo	Phase 3

Detailed Description

This is a 3-part Phase 3 study, with Part A (Blinded Phase), Part B (Open-label Observational Phase), and Part C (Booster Dose Phase). Participants in Part A are blinded to their treatment assignment, with participants receiving either mRNA-1273 vaccine or placebo. Part B of the study is designed to offer participants to be unblinded so that participants who received placebo in Part A can request 2 doses of open-label mRNA-1273 vaccine. Additionally, participants who choose to be unblinded and were only able to receive 1 dose of mRNA-1273 due to administrative reasons, can choose to receive the second dose of mRNA-1273 during Part B. In Part C, a booster dose will be provided for all eligible participants who choose to receive one.

Please access www.modernatx.com/cove-study for additional information, such as Study Overview, Participation, and Site Locations along with contact numbers for each location for the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Part A is observer-blind. Part B is open-label; participants can request to be unblinded by scheduling a Participant Decision clinic visit. Part C offers participants the option to receive a booster dose for those participants who received at least one dose of mRNA-1273 in the study.
• Primary Purpose: Prevention
• Official Title: A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older
• Actual Study Start Date: Jul 27, 2020
• Anticipated Primary Completion Date: Dec 29, 2022
• Anticipated Study Completion Date: Dec 29, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mRNA-1273 Part A (Blinded): Participants will receive 1 intramuscular (IM) injection of 100 microgram (μg) mRNA-1273 on Day 1 and on Day 29. Part B (Open-label): Participants who receive mRNA-1273-matching placebo during Part A and choose to be unblinded by participating in Part B, will receive 1 IM injection of 100 μg mRNA-1273 on Day 1 and Day 29. Participants who are only able to receive 1 dose of mRNA-1273 due to administrative reasons, will receive 1 IM injection of 100 μg mRNA-1273 on Day 1, if the participant chooses. Part C: Eligible participants in Part B who choose to receive booster dose of mRNA-1273, will receive 1 IM injection of 50 μg mRNA-1273 on Day 1.	Biological: mRNA-1273; Sterile liquid for injection; Biological: Placebo; 0.9% sodium chloride (normal saline) injection
Placebo Comparator: Placebo Part A only: Participants will receive 1 IM injection of mRNA-1273-matching placebo on Day 1 and on Day 29, if the participant chooses.	Biological: Placebo; 0.9% sodium chloride (normal saline) injection

Outcome Measures

Primary Outcome Measures

1. Efficacy: Number of Participants with a First Occurrence of COVID-19 Starting 14 Days after Second Dose of mRNA-1273 [Part A only: Day 43 (14 days after second dose) up to Day 759 (2 years after second dose)]

2. Safety: Number of Participants with Adverse Events (AEs) or Medically Attended AEs (MAAEs) Leading to Withdrawal [Up to Day 759 (2 years after second dose)]

3. Safety: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [Part A only: Up to Day 8 (7 days after first dose) and up to Day 36 (7 days after second dose)]

4. Safety: Number of Participants with Unsolicited AEs [Part A and C only: Up to Day 57 (28 days after each dose)]

5. Safety: Number of Participants with Serious AEs (SAEs) [Up to Day 759 (2 years after second dose)]

Secondary Outcome Measures

1. Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of mRNA-1273 or Placebo [Day 43 (14 days after second dose) up to Day 759 (2 years after second dose)]

   Clinical signs indicative of severe COVID-19 as predefined for the study.

2. Number of Participants with a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection regardless of symptomatology or Severity Starting 14 Days after Second Dose of mRNA-1273 or Placebo [Day 43 (14 days after second dose) up to Day 759 (2 years after second dose)]

   Clinical signs indicative of COVID-19 and SARS-CoV-2 Infection as predefined for the study.

3. Number of Participants with a Secondary Case Definition of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo [Day 43 (14 days after second dose) up to Day 759 (2 years after second dose)]

   Clinical signs indicative of secondary case definition of COVID-19 as predefined for the study.

4. Number of Participants with a First Occurrence of COVID-19 Starting 14 days after First Dose of mRNA-1273 or Placebo [Day 43 (14 days after first dose of the Blinded Phase) up to Day 759 (2 years after second dose)]

   Clinical signs indicative of COVID-19 as predefined for the study.

5. Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo Regardless of Evidence of Prior SARS-CoV-2 Infection [Day 43 (14 days after second dose) up to Day 759 (2 years after second dose)]

   Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study.

6. Number of Participants with a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo [Day 43 (14 days after second dose) up to Day 759 (2 years after second dose)]

   Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study.

7. Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) [Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759]

8. Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb [Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759]

9. Quantified Levels or GMT of S Protein-Specific Binding Antibody (bAb) [Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759]

10. GMFR of S Protein Specific bAb [Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759]

11. Number of Participants With Seroresponse Against SARS-CoV-2 (Part C Only) [Post-booster dose Day 29]

    Seroresponse is defined as a titer change from baseline (predose 1 in primary series) below the lower limit of quantitation (LLOQ) to ≥ 4 × LLOQ, or at least a 4-fold rise if baseline is ≥LLOQ.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• (Part A only) Participants who are at high risk of SARS-CoV-2 infection, defined as adults whose locations or circumstances put them at appreciable risk of exposure to SARS-CoV-2 and COVID-19.

• Understands and agrees to comply with the study procedures and provides written informed consent.

• Able to comply with study procedures based on the assessment of the Investigator.

• Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy) or postmenopausal (defined as amenorrhea for ≥12 consecutive months prior to Screening without an alternative medical cause). A follicle-stimulating hormone (FSH) level may be measured at the discretion of the Investigator to confirm postmenopausal status.

• Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:

• Has a negative pregnancy test at Screening and on the day of the first dose (Day 1, open-label Day 1, and booster dose Day 1).

• Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1).

• Has agreed to continue adequate contraception through 3 months following the last dose (Day 29, open-label Day 29, and booster dose Day 1).

• Is not currently breastfeeding.

• Healthy adults or adults with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment.

• (Part C Only) Is currently enrolled in Part B of the current study (mRNA-1273-P301).

• (Part C Only) Has received at least 1 dose of mRNA-1273 in the current study (mRNA-1273-P301).

Exclusion Criteria:

• Is acutely ill or febrile 72 hours prior to or at Screening or dosing (Part B and Part C). Fever is defined as a body temperature ≥38.0°Celsius/100.4°Fahrenheit. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled/dosed at the discretion of the Investigator.

• Is pregnant or breastfeeding.

• (Part A Only) Known history of SARS-CoV-2 infection.

• Prior (Part A) or concurrent (Part B and Part C) administration of non-study coronavirus (SARS-CoV, Middle East Respiratory Syndrome [MERS]-CoV) vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID-19.

• (Part A Only) Demonstrated inability to comply with the study procedures.

• An immediate family member or household member of this study's personnel.

• Known or suspected allergy or history of anaphylaxis, urticaria, or other significant adverse reaction to the vaccine or its excipients.

• Bleeding disorder considered a contraindication to intramuscular injection or phlebotomy.

• Has received or plans to receive a vaccine within 28 days prior to the first dose (Day

1. or plans to receive a non-study vaccine within 28 days prior to or after any dose of investigational product (IP) (except for seasonal influenza vaccine).

• (Part A only) Has participated in an interventional clinical study within 28 days prior to the day of enrollment.

• Immunosuppressive or immunodeficient state, including human immunodeficiency virus (HIV) infection, asplenia, and recurrent severe infections.

• Has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to IP dose administration (for corticosteroids ≥20 milligram (mg)/day of prednisone equivalent).

• Has received systemic immunoglobulins or blood products within 3 months prior to the day of IP dose administration.

• Has donated ≥450 milliliters (mL) of blood products within 28 days prior to IP dose administration.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ascension St. Vincent Birmingham	Birmingham	Alabama	United States	35205
2	Synexus Clinical Research US, Inc. - Birmingham	Birmingham	Alabama	United States	35211
3	Hope Research Institute	Chandler	Arizona	United States	85224
4	Synexus Clinical Research US, Inc. - Phoenix West	Glendale	Arizona	United States	85306
5	Hope Research Institute	Peoria	Arizona	United States	85018
6	Hope Research Institute	Phoenix	Arizona	United States	85018
7	Quality of Life Medical and Research Center	Tucson	Arizona	United States	85712
8	Baptist Health Center for Clinical Research	Little Rock	Arkansas	United States	72205
9	Advanced Clinical Research - Rancho Paseo	Banning	California	United States	92220
10	University of California San Diego	La Jolla	California	United States	92093
11	eStudySite - La Mesa	La Mesa	California	United States	91942
12	UCLA Vine Street Clinic CRS	Los Angeles	California	United States	90038
13	VA Greater Los Angeles Healthcare (veterans only)	Los Angeles	California	United States	90073
14	Paradigm Clinical Research Institute Inc	Redding	California	United States	96001
15	Benchmark Research - Sacramento	Sacramento	California	United States	95864
16	Medical Center For Clinical Research - M3 Wake Research	San Diego	California	United States	92108
17	University of Colorado Hospital	Aurora	Colorado	United States	80045
18	Lynn Institute of The Rockies	Colorado Springs	Colorado	United States	80918
19	George Washington University	Washington	District of Columbia	United States	20037
20	Accel Research Site	DeLand	Florida	United States	32720
21	Research Centers of America	Hollywood	Florida	United States	33024
22	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
23	Synexus - Optimal Research - Melbourne	Melbourne	Florida	United States	32934
24	Suncoast Research Group	Miami	Florida	United States	33135
25	University of Miami	Miami	Florida	United States	33136
26	Synexus Clinical Research US, Inc. - Orlando	Orlando	Florida	United States	32806
27	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
28	Grady Health System	Atlanta	Georgia	United States	30303
29	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
30	Hope Clinic of The Emory Vaccine Center	Decatur	Georgia	United States	30030
31	Meridian Clinical Research	Savannah	Georgia	United States	31406
32	Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
33	Synexus Clinical Research US, Inc. - Chicago	Chicago	Illinois	United States	60602
34	UIC Project WISH CRS	Chicago	Illinois	United States	60612
35	University of Chicago-Hospital	Chicago	Illinois	United States	60637
36	Johnson County Clin-Trials	Lenexa	Kansas	United States	66219
37	Alliance for Multispecialty Research	Newton	Kansas	United States	67114
38	Alliance for Multispecialty Research- East Wichita	Wichita	Kansas	United States	67207
39	Meridian Clinical Research	Baton Rouge	Louisiana	United States	70808
40	Benchmark Research - Metairie	Metairie	Louisiana	United States	70006
41	University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
42	Synexus - Optimal Research - Rockville	Rockville	Maryland	United States	20850
43	Meridian Clinical Research	Rockville	Maryland	United States	20854
44	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
45	Henry Ford Health System	Detroit	Michigan	United States	48202
46	MediSync Clinical Research Hattiesburg Clinic	Petal	Mississippi	United States	39465
47	Saint Louis University	Saint Louis	Missouri	United States	63104
48	Sundance Clinical Research	Saint Louis	Missouri	United States	63141
49	Meridian Clinical Research	Grand Island	Nebraska	United States	68803
50	Meridian Clinical Research	Norfolk	Nebraska	United States	68701
51	Meridian Clinical Research	Omaha	Nebraska	United States	68134
52	Clinical Research Center of Nevada	Las Vegas	Nevada	United States	89104
53	AB Clinical Trials	Las Vegas	Nevada	United States	89119
54	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
55	New Jersey Medical School	Newark	New Jersey	United States	07103
56	Meridian Clinical Research	Binghamton	New York	United States	13901
57	Weill Cornell Chelsea - (CRS)	New York	New York	United States	10010
58	Weill Cornell Medical College	New York	New York	United States	10065
59	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
60	Tryon Medical Partners	Charlotte	North Carolina	United States	28210
61	Carolina Institute for Clinical Research - M3 Wake Research	Fayetteville	North Carolina	United States	28304
62	M3 Wake Research, Inc - M3 Wake	Raleigh	North Carolina	United States	27612
63	Trial Management Associates	Wilmington	North Carolina	United States	28403
64	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
65	Synexus Clinical Research US, Inc. - Cincinnati	Cincinnati	Ohio	United States	45236
66	New Horizons Clinical Research	Cincinnati	Ohio	United States	45242
67	Cincinnati CRS	Cincinnati	Ohio	United States	45267
68	Rapid Medical Research Inc	Cleveland	Ohio	United States	44122
69	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States	73112
70	Crisor	Medford	Oregon	United States	97504
71	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
72	UPMC University Center	Pittsburgh	Pennsylvania	United States	15213
73	Keystone VitaLink Research	Anderson	South Carolina	United States	29621
74	Keystone VitaLink Research - Greenville	Greenville	South Carolina	United States	29615
75	Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	29464
76	Keystone VitaLink Research - Spartanburg	Spartanburg	South Carolina	United States	29303
77	Meridian Clinical Research	Dakota Dunes	South Dakota	United States	57049
78	WR-ClinSearch	Chattanooga	Tennessee	United States	37421
79	Alliance for Multispecialty Research	Knoxville	Tennessee	United States	39720
80	Vanderbilt University Medical Center, Medical Arts Building	Nashville	Tennessee	United States	37232
81	Vanderbilt University Medical Center, Medical Center North	Nashville	Tennessee	United States	37232
82	Benchmark Research - Austin	Austin	Texas	United States	78705
83	Synexus - Optimal Research - Austin	Austin	Texas	United States	78705
84	Tekton Research	Austin	Texas	United States	78745
85	Advanced Clinical Research - Be Well MD	Cedar Park	Texas	United States	78613
86	Global Medical Research - M3 Wake Research	Dallas	Texas	United States	75224
87	Synexus Clinical Research US, Inc. - Dallas	Dallas	Texas	United States	75234
88	Benchmark Research - Fort Worth	Fort Worth	Texas	United States	76135
89	University of Texas Medical Branch at Galveston	Galveston	Texas	United States	77555
90	Baylor College of Medicine	Houston	Texas	United States	77030
91	DM Clinical Research - Texas Center For Drug Development	Houston	Texas	United States	77081
92	Laguna Clinical Research	Laredo	Texas	United States	78041
93	Centex Studies	McAllen	Texas	United States	78504
94	Benchmark Research - San Angelo	San Angelo	Texas	United States	76904
95	Clinical Trials of Texas, Inc	San Antonio	Texas	United States	78229
96	DM Clinical Research	Tomball	Texas	United States	77375
97	Synexus Clinical Research US, Inc. - Salt Lake City	Murray	Utah	United States	84123
98	Foothill Family Clinic - North	Salt Lake City	Utah	United States	84109
99	Foothill Family Clinic-South Clinic	Salt Lake City	Utah	United States	84121
100	Kaiser Permanente - Seattle	Seattle	Washington	United States	98101

Sponsors and Collaborators

• ModernaTX, Inc.
• Biomedical Advanced Research and Development Authority
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here to access the website, www.modernatx.com/cove-study, for additional information for the study, such as Study Overview, Participation, and Site Locations, along with contact numbers for each location for the study.

Publications

None provided.

• Responsible Party: ModernaTX, Inc.
• ClinicalTrials.gov Identifier: NCT04470427
• Other Study ID Numbers: mRNA-1273-P301; 75A50120C00034
• First Posted: Jul 14, 2020
• Last Update Posted: May 19, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by ModernaTX, Inc.: mRNA-1273; mRNA-1273 vaccine; SARS-CoV-2; SARS-CoV-2 Vaccine; Coronavirus; Virus Diseases; Messenger RNA; COVID-19; COVID-19 Vaccine; Moderna

Study Results

No Results Posted as of May 19, 2022