A Study to Evaluate the Immunogenicity and Safety of Omicron Variant Vaccines in Comparison With mRNA-1273 Booster Vaccine for COVID-19

Study Overview
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Brief Summary
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This is a 2-part study to evaluate the immunogenicity, safety, and reactogenicity of mRNA-1273.529 and mRNA-1273.214 administered as a booster dose.

Detailed Description
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In Part 1, participants will be randomized in a 1:1 ratio to receive a single dose of either mRNA-1273.529 or mRNA-1273. In Part 2, participants will be randomized in a 1:1 ratio to receive a single dose of either mRNA-1273.214 or mRNA-1273. All participants will have previously received 2 or 3 doses of an authorized/approved COVID-19 vaccine. Participants who previously received 2 doses of a COVID-19 vaccine as a primary series will receive mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the 3rd dose, and participants who have previously received a primary series and 1 booster dose will receive mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the 4th dose (a mixed approach is acceptable). Each part will include Phase A (randomized, blinded) and Phase B (open-label, observational).

Official Title
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A Phase 2/3, Randomized, Observer-blind, Active-controlled, Multicenter Study to Evaluate the Immunogenicity and Safety of Omicron Variant Vaccines in Comparison With mRNA-1273 (Prototype) Booster Vaccine

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: mRNA-1273.529
* Biological: mRNA-1273
* Biological: mRNA-1273.214


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test at the Screening Visit and on the day of vaccination prior to vaccine dose being administered on 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); and has agreed to continue adequate contraception through 90 days following vaccine administration. Participant has received 2 prior doses of one of the following approved/authorized COVID-19 vaccines: Moderna, Pfizer/BioNTech, Oxford/AstraZeneca, Janssen. A heterologous vaccine regimen is acceptable. Participants who will receive the 4th dose as part of the study must have previously received a mRNA vaccine (Moderna or Pfizer/BioNTech) as the 3rd dose of a COVID-19 vaccine. Participants who will receive the 3rd dose as part of the study may have previously received 2 doses of an approved/authorized mRNA or a non-mRNA COVID-19 vaccine (a heterologous vaccine regimen is acceptable). Exclusion Criteria: Participant had close contact (without personal protective equipment [PPE]) as defined by the Centers for Disease Control and Prevention (CDC) in the past 14 days to someone diagnosed with SARS-CoV-2 infection or COVID-19 within 10 days of the close contact. Participants may be rescreened after 14 days provided that they remain asymptomatic. Participant is acutely ill or febrile (temperature ≥ 38.0°C/100.4°F) 72 hours prior to or at the Screening Visit or Day 1. Participant has tested positive for SARS-CoV-2 by an authorized/approved lateral flow/rapid antigen or polymerase chain reaction (PCR) test within 90 days of Screening. Participant has received a COVID-19 vaccine within 90 days of the Screening Visit. Participant has received a total of 4 doses or more of COVID-19 vaccine. Participant has received a COVID-19 vaccine at a dose different from the authorized/approved dose. Any medical, psychiatric, or occupational condition, including reported history of substance abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 181 days prior to screening (for corticosteroids ≥10 milligrams [mg]/day of prednisone or equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Participant has received or plans to receive any licensed vaccine ≤28 days prior to the study injection (Day 1) or plans to receive a licensed vaccine within 28 days after the study injection (with the exception that approved seasonal influenza vaccine may be received by at least 7 days and preferably 14 days apart from the study injection). Participant has received systemic immunoglobulins or blood products within 90 days prior to the Screening Visit or plans to receive during the study. Participant has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study. Participant has participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study. Note: Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 16 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
Interventional Model Description: Phase A of this study will be observer-blinded. Phase B of the study will be open-label and blinding is not applicable
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: mRNA-1273.529<br>Phase A: Participants will receive 1 intramuscular (IM) dose of mRNA-1273.529 on Day 1. Phase B: After Day 179, eligible participants may choose to be unblinded and to receive an additional booster outside of the study. | Biological: mRNA-1273.529<br>* Sterile liquid for injection<br>|
| Active Comparator: Part 1: mRNA-1273<br>Phase A: Participants will receive 1 IM dose of mRNA-1273 on Day 1. Phase B: After Day 179, eligible participants may choose to be unblinded and to receive an additional booster outside of the study. | Biological: mRNA-1273<br>* Sterile liquid for injection<br>|
| Experimental: Part 2: mRNA-1273.214<br>Phase A: Participants will receive 1 IM dose of mRNA-1273.214 on Day 1. Phase B: After Day 85, eligible participants may choose to be unblinded and to receive an additional booster outside of the study. | Biological: mRNA-1273.214<br>* Sterile liquid for injection<br>|
| Active Comparator: Part 2: mRNA-1273<br>Phase A: Participants will receive 1 IM dose of mRNA-1273 on Day 1. Phase B: After Day 85, eligible participants may choose to be unblinded and to receive an additional booster outside of the study. | Biological: mRNA-1273<br>* Sterile liquid for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain |  | Up to Day 85 post-vaccination | 
| Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) |  | Up to Day 8 (7 days post-vaccination) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 29 (28 days post-vaccination) | 
| Number of Participants with Serious AEs (SAEs) |  | Day 1 to end of study (Day 359) | 
| Number of Participants with Medically Attended AEs (MAAEs) |  | Day 1 to end of study (Day 359) | 
| Number of Participants with AEs Leading to Withdrawal |  | Day 1 to end of study (Day 359) | 
| Number of Participants with AEs of Special Interest (AESIs) |  | Day 1 to end of study (Day 359) | 
| GMT of mRNA-1273.214 and mRNA-1273 Against the B1.1.529 Strain |  | Up to Day 85 post-vaccination | 
| GMT of mRNA-1273.214 and mRNA-1273 Against the Prototype Strain |  | Up to Day 85 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain |  | Days 1, 29, 85, 179, and 359 | 
| GMT of mRNA-1273.529 and mRNA-1273 Against the Prototype Strain |  | Days 1, 29, 85, 179, and 359 | 
| Seroresponse Rate of Vaccine Recipients |  | Days 1, 29, 85, 179, and 359 | 
| GMT of mRNA-1273.214 and mRNA-1273 Against Other Variant Strains |  | Days 29 and 85 | 
| Number of Participants with Asymptomatic SARS-CoV-2 Infection Measured by Reverse Transcriptase Polymerase-chain Reaction (RT-PCR) |  | Day 1 through the end of study (Day 359) | 
| Number of Participants with Symptomatic SARS-CoV-2 Infection Measured by RT-PCR |  | Day 1 through the end of study (Day 359) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Messenger RNA, Spikevax, mRNA-1273, mRNA-1273 vaccine, mRNA-1273.529, mRNA-1273.529 vaccine, Omicron, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, COVID-19, COVID-19 Vaccine, Moderna, Multivalent Vaccine, Variant Strains