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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: mRNA-1273
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1273<br>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<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Placebo Comparator: Placebo<br>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<br>* 0.9% sodium chloride (normal saline) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| Safety: Number of Participants with Unsolicited AEs |  | Part A and C only: Up to Day 57 (28 days after each dose) | 
| Safety: Number of Participants with Serious AEs (SAEs) |  | Up to Day 759 (2 years after second dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of mRNA-1273 or Placebo | Clinical signs indicative of severe COVID-19 as predefined for the study. | Day 43 (14 days after second dose) up to Day 759 (2 years after second dose) | 
| 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 | Clinical signs indicative of COVID-19 and SARS-CoV-2 Infection as predefined for the study. | Day 43 (14 days after second dose) up to Day 759 (2 years after second dose) | 
| Number of Participants with a Secondary Case Definition of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo | Clinical signs indicative of secondary case definition of COVID-19 as predefined for the study. | Day 43 (14 days after second dose) up to Day 759 (2 years after second dose) | 
| Number of Participants with a First Occurrence of COVID-19 Starting 14 days after First Dose of mRNA-1273 or Placebo | Clinical signs indicative of COVID-19 as predefined for the study. | Day 43 (14 days after first dose of the Blinded Phase) up to Day 759 (2 years after second dose) | 
| 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 | Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study. | Day 43 (14 days after second dose) up to Day 759 (2 years after second dose) | 
| 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 | Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study. | Day 43 (14 days after second dose) up to Day 759 (2 years after second dose) | 
| 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 | 
| Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb |  | Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759 | 
| Quantified Levels or GMT of S Protein-Specific Binding Antibody (bAb) |  | Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759 | 
| GMFR of S Protein Specific bAb |  | Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759 | 
| Number of Participants With Seroresponse Against SARS-CoV-2 (Part C Only) | 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. | Post-booster dose Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-1273, mRNA-1273 vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna