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

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

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.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2
• Intervention / Treatment: Biological: Placebo; Biological: mRNA-1273

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 Type: Interventional
• Enrollment (Actual): 30415
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Ascension St. Vincent Birmingham
    • Birmingham, Alabama, United States, 35211
      • Synexus Clinical Research US, Inc. - Birmingham
  • Arizona
    • Chandler, Arizona, United States, 85224
      • HOPE Research Institute
    • Glendale, Arizona, United States, 85306
      • Synexus Clinical Research US, Inc. - Phoenix West
    • Peoria, Arizona, United States, 85018
      • HOPE Research Institute
    • Phoenix, Arizona, United States, 85018
      • HOPE Research Institute
    • Tucson, Arizona, United States, 85712
      • Quality of Life Medical and Research Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research
  • California
    • Banning, California, United States, 92220
      • Advanced Clinical Research - Rancho Paseo
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • La Mesa, California, United States, 91942
      • eStudySite - La Mesa
    • Los Angeles, California, United States, 90038
      • UCLA Vine Street Clinic CRS
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare (veterans only)
    • Redding, California, United States, 96001
      • Paradigm Clinical Research Institute Inc
    • Sacramento, California, United States, 95864
      • Benchmark Research - Sacramento
    • San Diego, California, United States, 92108
      • Medical Center For Clinical Research - M3 Wake Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Colorado Springs, Colorado, United States, 80918
      • Lynn Institute Of The Rockies
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University
  • Florida
    • DeLand, Florida, United States, 32720
      • Accel Research Site
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Melbourne, Florida, United States, 32934
      • Synexus - Optimal Research - Melbourne
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33135
      • Suncoast Research Group
    • Orlando, Florida, United States, 32806
      • Synexus Clinical Research US, Inc. - Orlando
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Decatur, Georgia, United States, 30030
      • Hope Clinic of The Emory Vaccine Center
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • UIC Project WISH CRS
    • Chicago, Illinois, United States, 60602
      • Synexus Clinical Research US, Inc. - Chicago
    • Chicago, Illinois, United States, 60637
      • University of Chicago-Hospital
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty Research
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research- East Wichita
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Meridian Clinical Research
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research - Metairie
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
    • Rockville, Maryland, United States, 20850
      • Synexus - Optimal Research - Rockville
    • Rockville, Maryland, United States, 20854
      • Meridian Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Mississippi
    • Petal, Mississippi, United States, 39465
      • MediSync Clinical Research Hattiesburg Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Meridian Clinical Research
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • AB Clinical Trials
    • Las Vegas, Nevada, United States, 89104
      • Clinical Research Center of Nevada
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School
  • New York
    • Binghamton, New York, United States, 13901
      • Meridian Clinical Research
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10010
      • Weill Cornell Chelsea - (CRS)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28210
      • Tryon Medical Partners
    • Fayetteville, North Carolina, United States, 28304
      • Carolina Institute for Clinical Research - M3 Wake Research
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc - M3 Wake
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • New Horizons Clinical Research
    • Cincinnati, Ohio, United States, 45236
      • Synexus Clinical Research US, Inc. - Cincinnati
    • Cincinnati, Ohio, United States, 45267
      • Cincinnati CRS
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research Inc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Oregon
    • Medford, Oregon, United States, 97504
      • Crisor
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC University Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Keystone VitaLink Research
    • Greenville, South Carolina, United States, 29615
      • Keystone VitaLink Research - Greenville
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
    • Spartanburg, South Carolina, United States, 29303
      • Keystone VitaLink Research - Spartanburg
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • Meridian Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch
    • Knoxville, Tennessee, United States, 39720
      • Alliance for Multispecialty Research
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center, Medical Arts Building
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center, Medical Center North
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research
    • Austin, Texas, United States, 78705
      • Benchmark Research - Austin
    • Austin, Texas, United States, 78705
      • Synexus - Optimal Research - Austin
    • Cedar Park, Texas, United States, 78613
      • Advanced Clinical Research - Be Well MD
    • Dallas, Texas, United States, 75224
      • Global Medical Research - M3 Wake Research
    • Dallas, Texas, United States, 75234
      • Synexus Clinical Research US, Inc. - Dallas
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research - Fort Worth
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch at Galveston
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77081
      • DM Clinical Research - Texas Center For Drug Development
    • Laredo, Texas, United States, 78041
      • Laguna Clinical Research
    • McAllen, Texas, United States, 78504
      • Centex Studies
    • San Angelo, Texas, United States, 76904
      • Benchmark Research - San Angelo
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • Murray, Utah, United States, 84123
      • Synexus Clinical Research US, Inc. - Salt Lake City
    • Salt Lake City, Utah, United States, 84121
      • Foothill Family Clinic-South Clinic
    • Salt Lake City, Utah, United States, 84109
      • Foothill Family Clinic - North
  • Washington
    • Seattle, Washington, United States, 98101
      • Kaiser Permanente - Seattle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Placebo; 0.9% sodium chloride (normal saline) injection; Biological: mRNA-1273; Sterile liquid for 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose	COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met.	From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose	Solicited ARs (local and systemic) were collected in electronic diary (eDiary) within 7 days of dosing. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Severity grading for solicited ARs is based on modified Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Severity was graded 0-4; a lower score indicated lower severity and a higher score indicated greater severity. The Investigator determined if solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is in Reported "Adverse Events" section.	up to Day 7 (7 days after first dose)
Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose	Solicited ARs (local and systemic) were collected in eDiary within 7 days of dosing. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Severity grading for solicited ARs is based on modified Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Severity was graded 0-4; lower score indicated lower severity and a higher score indicated greater severity. The Investigator determined if solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is in Reported "Adverse Events" section	Day 29 to Day 35 (from second dose to 7 days after second dose)
Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation	An MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner (HCP). A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Day 1 (after dosing) through end of study (up to Day 759)
Parts A and B: Number of Participants With Serious AEs (SAEs)	An SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Day 1 (after dosing) through end of study (up to Day 759)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of Participants With Unsolicited AEs up to 28 Days After Any Injection Dose	Unsolicited AE was any AE reported by the participant that was not specified as an AR or was specified as a solicited AR in the protocol but started outside the protocol-defined, post-injection period for reporting solicited ARs. Unsolicited AEs were collected for the 28 days after any injection. An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all SAEs and all nonserious AEs ("Other") reported up to the end of the study, regardless of causality, is located in the Reported "Adverse Events" section.	Up to 28 days after any dose
Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose	COVID-19 cases were defined as participants meeting clinical criteria based on symptoms for COVID-19 and reverse transcriptase polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 from samples collected within 72 hours of the participant reporting symptoms meeting the definition of COVID-19. An adjudication committee reviewed potential cases to determine if the criteria for COVID-19 were met. Clinical signs indicative of severe COVID-19 systemic illness included any of the following: respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, oxygen saturation (SpO2) ≤93% on room air at sea level, or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FIO2) <300 millimeter of mercury (mm Hg), or respiratory failure or acute respiratory distress syndrome (ARDS), evidence of shock, or significant acute renal, hepatic, or neurologic dysfunction, or admission to an intensive care unit or death.	From Day 43 (14 days after second dose) up to approximately 8 months for Part A and from PDV/unblinding (at 4 months) to up to 8 months for Part B
Part A: 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	COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met. SARS-CoV-2 infection was defined by seroconversion due to infection measured by binding antibody (bAb) levels against SARS-CoV-2 nucleocapsid or by positive RT-PCR at predefined timepoints. Seroconversion was defined by the participant's serostatus at baseline.	From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Part A: Number of Participants With a Secondary Case Definition of COVID-19 Starting 14 Days After Second Dose	Secondary case definition of COVID-19 was defined as the presence of at least 1 of the following systemic symptoms: fever (temperature ≥38ºC), or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, nasal congestion or rhinorrhea, nausea or vomiting, or diarrhea and a positive nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) for SARS-CoV-2 by RT-PCR.	From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose		From Day 43 (14 days after second dose) up to approximately 8 months for Part A and from PDV/unblinding (at 4 months) to up to 8 months for Part B
Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After First Dose	COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met.	From 14 days after first dose up to approximately 8 months
Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose Regardless of Evidence of Prior SARS-CoV-2 Infection	COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met.	From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Part A: 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	SARS-CoV-2 infection was defined by seroconversion due to infection measured by binding antibody (bAb) levels against SARS-CoV-2 nucleocapsid or by positive RT-PCR at predefined timepoints. Seroconversion was defined by the participant's serostatus at baseline.	From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)	GMT (50% inhibitory dose [ID50], 80% inhibitory dose [ID80]) of nAb against SARS-CoV-2 pseudotyped viruses as measured by pseudovirus nAb assay is reported. 95% CI was based on the t-distribution of log-transformed values for GM titer, then back transformed to original scale for presentation. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1.	Day 1, Day 29, Day 57
Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb	The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. 95% CI was calculated based on the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation. GMFR for ID50 and ID80 neutralizing antibodies against SARS-CoV-2 S-protein, as measured by pseudovirus neutralizing antibody is presented. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1	Day 29, Day 57
Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2	Seroresponse to pseudovirus neutralizing antibody ID50 titer at a participant level is defined as a change from below the LLOQ to equal or above the LLOQ, or at least a 3.3-fold rise if baseline is equal to or above the LLOQ. Seroresponse to pseudovirus neutralizing antibody ID80 titer at a participant level is defined as a change from below the LLOQ to equal or above the LLOQ, or at least a 2.3-fold rise if baseline is equal to or above the LLOQ. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1.	Day 29, Day 57
Part C: GMT of SARS-CoV-2 Specific nAb Measured by Pseudovirus (VAC62)	95% CI is calculated based on the t-distribution of the log-transformed values for GM value, then back transformed to the original scale for presentation.	Pre-booster (Baseline), post-booster Day 29 and post-booster Day 181
Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 Measured by Pseudovirus (VAC62)	Pseudovirus neutralizing antibody (VAC62) from pre-booster is presented. Seroresponse at a participant level is defined as a change from below the LLOQ to >= 4 x LLOQ, or at least a 4-fold rise if pre-booster is equal to or above the LLOQ.	Post-booster Day 29 and post-booster Day 181
Part C: Geometric Mean Concentration (GMC) of SARS-CoV-2 Specific nAb After BD Compared to After Second Dose in Part A Measured by Pseudovirus (VAC62)	95% CI is calculated based on the t-distribution of the log-transformed values for GMC, then back transformed to the original scale for presentation.	Part C BD Day 29 and Part A Day 57
Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 After BD Compared to After Second Dose in Part A	Pseudovirus neutralizing antibody (VAC62) are presented. Seroresponse at a participant level is defined as a change from below the LLOQ to equal or above 4 x LLOQ, or at least a4-fold rise if baseline (Pre- Dose 1) is equal to or above the LLOQ.	Part C BD Day 29 and Part A Day 57

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Fraiman J, Erviti J, Jones M, Greenland S, Whelan P, Kaplan RM, Doshi P. Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults. Vaccine. 2022 Sep 22;40(40):5798-5805. doi: 10.1016/j.vaccine.2022.08.036. Epub 2022 Aug 31.
• Follmann D, Janes HE, Buhule OD, Zhou H, Girard B, Marks K, Kotloff K, Desjardins M, Corey L, Neuzil KM, Miller JM, El Sahly HM, Baden LR. Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial. Ann Intern Med. 2022 Sep;175(9):1258-1265. doi: 10.7326/M22-1300. Epub 2022 Jul 5.
• El Sahly HM, Baden LR, Essink B, Montefiori D, McDermont A, Rupp R, Lewis M, Swaminathan S, Griffin C, Fragoso V, Miller VE, Girard B, Paila YD, Deng W, Tomassini JE, Paris R, Schodel F, Das R, August A, Leav B, Miller JM, Zhou H, Pajon R; Coronavirus Efficacy (COVE) Study Group. Humoral Immunogenicity of the mRNA-1273 Vaccine in the Phase 3 Coronavirus Efficacy (COVE) Trial. J Infect Dis. 2022 Nov 11;226(10):1731-1742. doi: 10.1093/infdis/jiac188.
• Pajon R, Paila YD, Girard B, Dixon G, Kacena K, Baden LR, El Sahly HM, Essink B, Mullane KM, Frank I, Denhan D, Kerwin E, Zhao X, Ding B, Deng W, Tomassini JE, Zhou H, Leav B, Schodel F; COVE Trial Consortium. Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial. Nat Med. 2022 Apr;28(4):823-830. doi: 10.1038/s41591-022-01679-5. Epub 2022 Feb 10.
• El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, Campbell TB, Clark J, Jackson LA, Fichtenbaum CJ, Zervos M, Rankin B, Eder F, Feldman G, Kennelly C, Han-Conrad L, Levin M, Neuzil KM, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Polakowski L, Mascola JR, Ledgerwood JE, Graham BS, August A, Clouting H, Deng W, Han S, Leav B, Manzo D, Pajon R, Schodel F, Tomassini JE, Zhou H, Miller J; COVE Study Group. Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase. N Engl J Med. 2021 Nov 4;385(19):1774-1785. doi: 10.1056/NEJMoa2113017. Epub 2021 Sep 22.
• Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 Feb 4;384(5):403-416. doi: 10.1056/NEJMoa2035389. Epub 2020 Dec 30.
• Gilbert PB, Montefiori DC, McDermott A, Fong Y, Benkeser D, Deng W, Zhou H, Houchens CR, Martins K, Jayashankar L, Castellino F, Flach B, Lin BC, O'Connell S, McDanal C, Eaton A, Sarzotti-Kelsoe M, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi N, Huynh C, Miller J, El Sahly HM, Baden LR, Baron M, De La Cruz L, Gay C, Kalams S, Kelley CF, Kutner M, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Carpp LN, Pajon R, Follmann D, Donis RO, Koup RA. Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial. medRxiv [Preprint]. 2021 Aug 15:2021.08.09.21261290. doi: 10.1101/2021.08.09.21261290.

Helpful Links

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2020
• Primary Completion (Actual): December 29, 2022
• Study Completion (Actual): December 29, 2022

Study Registration Dates

• First Submitted: July 11, 2020
• First Submitted That Met QC Criteria: July 11, 2020
• First Posted (Actual): July 14, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; COVID-19; SARS-CoV-2 Vaccine; Virus Diseases; Moderna; Messenger RNA; COVID-19 Vaccine; mRNA-1273 vaccine; mRNA-1273
• Other Study ID Numbers: mRNA-1273-P301; 75A50120C00034 (Other Grant/Funding Number: BARDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No