Clinical trial NCT04470427: A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS-CoV-2
Keywords: mRNA-1273
mRNA-1273 vaccine
SARS-CoV-2
SARS-CoV-2 Vaccine
Coronavirus
Virus Diseases
Messenger RNA
COVID-19
COVID-19 Vaccine
Moderna
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2020-07-14
Enrollment: 30415
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose
timeFrame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
measure: Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose
timeFrame: up to Day 7 (7 days after first dose)
measure: Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose
timeFrame: Day 29 to Day 35 (from second dose to 7 days after second dose)
measure: Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation
timeFrame: Day 1 (after dosing) through end of study (up to Day 759)
measure: Parts A and B: Number of Participants With Serious AEs (SAEs)
timeFrame: Day 1 (after dosing) through end of study (up to Day 759)
Secondary outcomes:
measure: Part A: Number of Participants With Unsolicited AEs up to 28 Days After Any Injection Dose
timeFrame: Up to 28 days after any dose
measure: Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose
timeFrame: 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
measure: 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
timeFrame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
measure: Part A: Number of Participants With a Secondary Case Definition of COVID-19 Starting 14 Days After Second Dose
timeFrame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
measure: 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
timeFrame: 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
measure: Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After First Dose
timeFrame: From 14 days after first dose up to approximately 8 months
measure: 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
timeFrame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
measure: 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
timeFrame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
measure: Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)
timeFrame: Day 1, Day 29, Day 57
measure: Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb
timeFrame: Day 29, Day 57
measure: Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2
timeFrame: Day 29, Day 57
measure: Part C: GMT of SARS-CoV-2 Specific nAb Measured by Pseudovirus (VAC62)
timeFrame: Pre-booster (Baseline), post-booster Day 29 and post-booster Day 181
measure: Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 Measured by Pseudovirus (VAC62)
timeFrame: Post-booster Day 29 and post-booster Day 181
measure: 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)
timeFrame: Part C BD Day 29 and Part A Day 57
measure: Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 After BD Compared to After Second Dose in Part A
timeFrame: Part C BD Day 29 and Part A Day 57
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Ascension St. Vincent Birmingham
state: Alabama
city: Birmingham
country: United States
facility: Synexus Clinical Research US, Inc. - Birmingham
state: Alabama
city: Chandler
country: United States
facility: Hope Research Institute
state: Arizona
city: Glendale
country: United States
facility: Synexus Clinical Research US, Inc. - Phoenix West
state: Arizona
city: Peoria
country: United States
facility: Hope Research Institute
state: Arizona
city: Phoenix
country: United States
facility: Hope Research Institute
state: Arizona
city: Tucson
country: United States
facility: Quality of Life Medical and Research Center
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Banning
country: United States
facility: Advanced Clinical Research - Rancho Paseo
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: La Mesa
country: United States
facility: eStudySite - La Mesa
state: California
city: Los Angeles
country: United States
facility: UCLA Vine Street Clinic CRS
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare (veterans only)
state: California
city: Redding
country: United States
facility: Paradigm Clinical Research Institute Inc
state: California
city: Sacramento
country: United States
facility: Benchmark Research - Sacramento
state: California
city: San Diego
country: United States
facility: Medical Center For Clinical Research - M3 Wake Research
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Lynn Institute of The Rockies
state: Colorado
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: DeLand
country: United States
facility: Accel Research Site
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Melbourne
country: United States
facility: Synexus - Optimal Research - Melbourne
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Synexus Clinical Research US, Inc. - Orlando
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Decatur
country: United States
facility: Hope Clinic of The Emory Vaccine Center
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Chicago
country: United States
facility: Synexus Clinical Research US, Inc. - Chicago
state: Illinois
city: Chicago
country: United States
facility: UIC Project WISH CRS
state: Illinois
city: Chicago
country: United States
facility: University of Chicago-Hospital
state: Illinois
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Newton
country: United States
facility: Alliance for Multispecialty Research
state: Kansas
city: Wichita
country: United States
facility: Alliance for Multispecialty Research- East Wichita
state: Kansas
city: Baton Rouge
country: United States
facility: Meridian Clinical Research
state: Louisiana
city: Metairie
country: United States
facility: Benchmark Research - Metairie
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Rockville
country: United States
facility: Synexus - Optimal Research - Rockville
state: Maryland
city: Rockville
country: United States
facility: Meridian Clinical Research
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Petal
country: United States
facility: MediSync Clinical Research Hattiesburg Clinic
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Grand Island
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Norfolk
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: AB Clinical Trials
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Newark
country: United States
facility: New Jersey Medical School
state: New Jersey
city: Binghamton
country: United States
facility: Meridian Clinical Research
state: New York
city: New York
country: United States
facility: Weill Cornell Chelsea - (CRS)
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Tryon Medical Partners
state: North Carolina
city: Fayetteville
country: United States
facility: Carolina Institute for Clinical Research - M3 Wake Research
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc - M3 Wake
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Synexus Clinical Research US, Inc. - Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research Inc
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Medford
country: United States
facility: Crisor
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC University Center
state: Pennsylvania
city: Anderson
country: United States
facility: Keystone VitaLink Research
state: South Carolina
city: Greenville
country: United States
facility: Keystone VitaLink Research - Greenville
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Spartanburg
country: United States
facility: Keystone VitaLink Research - Spartanburg
state: South Carolina
city: Dakota Dunes
country: United States
facility: Meridian Clinical Research
state: South Dakota
city: Chattanooga
country: United States
facility: WR-ClinSearch
state: Tennessee
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Medical Arts Building
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Medical Center North
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research - Austin
state: Texas
city: Austin
country: United States
facility: Synexus - Optimal Research - Austin
state: Texas
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: Cedar Park
country: United States
facility: Advanced Clinical Research - Be Well MD
state: Texas
city: Dallas
country: United States
facility: Global Medical Research - M3 Wake Research
state: Texas
city: Dallas
country: United States
facility: Synexus Clinical Research US, Inc. - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research - Fort Worth
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: DM Clinical Research - Texas Center For Drug Development
state: Texas
city: Laredo
country: United States
facility: Laguna Clinical Research
state: Texas
city: McAllen
country: United States
facility: Centex Studies
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research - San Angelo
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Murray
country: United States
facility: Synexus Clinical Research US, Inc. - Salt Lake City
state: Utah
city: Salt Lake City
country: United States
facility: Foothill Family Clinic - North
state: Utah
city: Salt Lake City
country: United States
facility: Foothill Family Clinic-South Clinic
state: Utah
city: Seattle
country: United States
facility: Kaiser Permanente - Seattle
state: Washington
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.