A Study of mRNA-1083 (SARS-Cov-2 and Influenza) Vaccine in Healthy Adult Participants, ≥50 Years of Age

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity, safety, and reactogenicity of mRNA-1083 as compared with active control, co-administered licensed influenza and severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) vaccines, in 2 independent age-group sub-study cohorts, healthy adults 65 years and older (Cohort A) and healthy adults 50 to <65 years of age (Cohort B).

Official Title
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A Phase 3, Randomized, Observer-Blind, Active-Control Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1083 (SARS-Cov-2 and Influenza) Vaccine in Healthy Adult Participants, ≥50 Years of Age

Conditions
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SARS-CoV-2, Influenza

Intervention / Treatment
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* Biological: mRNA-1083
* Biological: Placebo
* Biological: Influenza Vaccine
* Biological: COVID-19 Vaccine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy adults either ≥65 years of age (Cohort A) or 50 to <65 years of age (Cohort B) at the time of consent (Screening Visit). For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, and agreement to continue adequate contraception through 3 months following vaccine administration. Fully vaccinated for COVID-19 primary series according to the locally authorized or approved regimen, and their last COVID-19 vaccine (primary series or booster) was ≥90 days prior to Day 1. Exclusion Criteria: Participant is acutely ill or febrile (temperature ≥38.0 degrees Celsius [°C]/100.4 degrees Fahrenheit [°F]) 72 hours prior to or at the Screening Visit or Day 1. Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol 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 for >14 days in total within 180 days prior to Day 1 (for corticosteroids, ≥10 milligrams [mg]/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study. Inhaled nasal and topical steroids are allowed. Received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to study injections or plans to receive a vaccine authorized or approved by a local health agency within 28 days after the study injections. Received a seasonal influenza vaccine ≤150 days prior to Day 1. Tested positive for influenza by local health authority-approved testing methods ≤150 days prior to Day 1. Has had close contact to someone with COVID-19 as defined by the Centers for Disease Control and Prevention (CDC) in the past 10 days prior to Day 1. 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. Note: Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 50 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: Cohort A1: mRNA-1083 and Placebo<br>Participants of age 65 years and older will receive mRNA-1083 and placebo administered as 2 intramuscular (IM) injections of on Day 1. | Biological: mRNA-1083<br>* Suspension for injection<br>Biological: Placebo<br>* 0.9% sodium chloride suspension for injection<br>|
| Active Comparator: Cohort A2: Influenza Vaccine and COVID-19 Vaccine<br>Participants of age 65 years and older will receive age recommended quadrivalent influenza vaccine and COVID-19 vaccine administered as 2 IM injections on Day 1. | Biological: Influenza Vaccine<br>* Commercially available formulation (Suspension for injection [pre-filled syringe])<br>Biological: COVID-19 Vaccine<br>* Commercially available formulation (Suspension for injection)<br>|
| Experimental: Cohort B1: mRNA-1083 and Placebo<br>Participants of age 50 to <65 years will receive mRNA-1083 and placebo administered as 2 IM injections of on Day 1. | Biological: mRNA-1083<br>* Suspension for injection<br>Biological: Placebo<br>* 0.9% sodium chloride suspension for injection<br>|
| Active Comparator: Cohort B2: Influenza Vaccine and COVID-19 Vaccine<br>Participants of age 50 to <65 years will receive age recommended quadrivalent influenza vaccine and COVID-19 vaccine administered as 2 IM injections on Day 1. | Biological: Influenza Vaccine<br>* Commercially available formulation (Suspension for injection [pre-filled syringe])<br>Biological: COVID-19 Vaccine<br>* Commercially available formulation (Suspension for injection)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay |  | Day 29 | 
| GM Level of Antibodies for SARS-CoV-2, as Measured by Pseudovirus Neutralization Assay (PsVNA) |  | Day 29 | 
| Influenza: Percentage of Participants with Seroconversion, as Measured by HAI Assay | Seroconversion is defined as a Day 29 post-injection level ≥1:40 if baseline is <1:10 or a 4-fold or greater rise if baseline is ≥1:10 in anti-HA antibodies measured by HAI assay. | Baseline to Day 29 | 
| SARS-CoV-2: Number of Participants with Seroresponse, as Measured by PsVNA | Seroresponse is defined as a Day 29 post-injection level ≥4-fold if baseline is ≥lower limit of quantification (LLOQ) or ≥4*LLOQ if baseline titer is <LLOQ in neutralizing antibody (nAb) values measured by PsVNA. | Baseline to Day 29 | 
| Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) |  | Up to 7 days after study injection | 
| Number of Participants With Unsolicited Adverse Events (AEs) |  | Up to 28 days after study injection | 
| Number of Participants With Medically Attended Adverse Events (MAAEs) |  | Day 1 through Day 181 | 
| Number of Participants With Adverse Events of Special Interest (AESIs) |  | Day 1 through Day 181 | 
| Number of Participants With Serious Adverse Events (SAEs) |  | Day 1 through Day 181 | 
| Number of Participants With AEs Leading to Discontinuation |  | Day 1 through Day 181 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay |  | Day 1, Day 29 | 
| GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA |  | Day 1, Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-1083, mRNA-1083 Vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, Influenza Vaccine, Moderna