A Study of Modified mRNA Vaccines in Healthy Adults

Study Overview
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Brief Summary
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The main goal of this study is to evaluate the safety, reactogenicity, and immunogenicity of study vaccines.

Official Title
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Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Modified mRNA Vaccines Using a Systems Biology Approach in Healthy Adults

Conditions
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SARS-CoV-2, Seasonal Influenza, Respiratory Syncytial Virus, Cytomegalovirus

Intervention / Treatment
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* Biological: mRNA-1273
* Biological: mRNA-1010
* Biological: mRNA-1345
* Biological: FLUAD®
* Biological: mRNA-1647


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18 to 75 years of age at the time of consent (screening visit) who, in the opinion of the investigator, are in good health based on review of medical history and physical examination performed at screening. For mRNA-1647 study arms, adults 18 to <50 years of age at the time of consent (screening visit) who, in the opinion of the investigator, are in good health based on review of medical history and physical examination performed at screening. Body mass index (BMI) of 18 kilograms (kg)/square meter (m^2) to 35 kg/m^2 (inclusive) at the screening visit. Exclusion Criteria: Participant has had close contact to someone with confirmed SARS-CoV-2, respiratory syncytial virus (RSV), or influenza infection in the past 14 days prior to the screening visit. Severe allergic reaction to any component of the FLUAD vaccine (active comparator), including egg protein, or after a previous dose of any influenza vaccine. Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to screening (to include any systemic corticosteroids) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Participant plans to receive any licensed or authorized vaccine, including COVID-19 influenza vaccines, within 28 days before or after any study injection. Participant has received a NH 2021 - 2022 or 2022-2023 seasonal influenza vaccine or any other influenza vaccine, or an experimental RSV or cytomegalovirus (CMV) vaccine, within 6 months prior to study Day 1, and/or has not completed a primary vaccination series for COVID-19. Participant has received an authorized or approved COVID-19 vaccine within 4 months prior to Day 1, and/or has not completed a primary vaccination series for COVID-19. Participant had a laboratory-confirmed infection with influenza or RSV within 6 months prior to Day 1, or SARS-CoV-2 within 4 months of Day 1. SARS-CoV-2 infection confirmed with self-administered, authorized or approved rapid antigen test is acceptable. 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. 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 until 12 months after their last study vaccination. Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: mRNA-1345<br>Participants will receive single intramuscular (IM) injection of mRNA-1345 on Day 1. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: Part 1: mRNA-1647 2-Dose<br>Participants will receive single IM injection of mRNA-1647 on Days 1 and 57. | Biological: mRNA-1647<br>* Sterile lyophilized product<br>|
| Experimental: Part 1: mRNA-1647 3-Dose<br>Participants will receive single IM injection of mRNA-1647 on Days 1, 57, and 169. | Biological: mRNA-1647<br>* Sterile lyophilized product<br>|
| Experimental: Part 2: mRNA-1273<br>Participants will receive single IM injection of mRNA-1273 on Day 1 | Biological: mRNA-1273<br>* Sterile liquid for injection<br>|
| Experimental: Part 2: mRNA-1010<br>Participants will receive single IM injection of mRNA-1010 on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>|
| Active Comparator: Part 2: FLUAD®<br>Participants will receive single IM injection of FLUAD® on Day 1. | Biological: FLUAD®<br>* adjuvanted (MF59), inactivated, quadrivalent seasonal influenza vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) |  | Up to Day 176 (7 days follow-up post-vaccination) | 
| Number of Participants With Unsolicited Adverse Events (AEs) |  | Up to Day 197 (28 days follow-up post-vaccination) | 
| Number of Participants With Serious AEs (SAEs), AEs of Special Interest (AESIs), and AEs Leading to Study Withdrawal or Discontinuation of Study Vaccination |  | Day 1 through end of study (EOS) (up to Day 1249) | 
| Number of Participants with Medically Attended Adverse Events (MAAEs) |  | Day 1 through Day 361 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Serum Neutralizing Antibody Response for mRNA-1010 (and Licensed Influenza Vaccine Comparator), mRNA-1273, and mRNA-1345 |  | Days 1 (Baseline), 29, 85, and 197 | 
| Geometric Mean Fold-Rise (GMFR) of Serum Neutralizing Antibody Response for mRNA-1010 (and Licensed Influenza Vaccine Comparator), mRNA-1273, and mRNA-1345 |  | Days 1 (Baseline), 29, 85, and 197 | 
| Percentage of Participants With Seroresponse for mRNA-1010 (and Licensed Influenza Vaccine Comparator), mRNA-1273, mRNA-1345, and mRNA-1647 |  | Days 1 (Baseline), 29, 85, and 197 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderna, mRNA-1273, mRNA-1273 vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Influenza vaccine, mRNA-1010, mRNA-1345, Respiratory syncytial virus, RSV Seropositive, Vaccines, mRNA-1647, Cytomegalovirus, CMV, Cytomegalovirus Vaccine, Cytomegalovirus Infections