A Study to Evaluate the Safety and Immune Response of mRNA-1345, a Vaccine Targeting Respiratory Syncytial Virus (RSV), When Co-administered With a Fluzone HD, in Adults ≥65 Years of Age

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and immunogenicity of mRNA-1345 RSV vaccine when coadministered with a high dose (HD) quadrivalent seasonal influenza vaccine (Fluzone HD) in adults ≥65 years of age. The study will examine the impact of Fluzone HD on the immune response to mRNA-1345 against RSV-A and RSV-B, as well as the impact of mRNA-1345 on the immune response to Fluzone HD against 4 vaccine-matched Influenza A and B strains.

Official Title
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A Phase 3, Randomized, Observer-Blind Study to Evaluate Safety, Tolerability, and Immunogenicity of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, When Coadministered With a High-Dose, Quadrivalent Seasonal Influenza Vaccine in Adults ≥65 Years of Age

Conditions
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Respiratory Syncytial Virus

Intervention / Treatment
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* Biological: Placebo
* Biological: mRNA-1345
* Biological: Fluzone HD


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants may have one or more chronic medical diagnoses, but should be medically stable as assessed by: Absence of changes in medical therapy within 60 days of Day 1 due to treatment failure or toxicity, Absence of serious or significant medical events within 30 days of Day 1, and Absence of known, current, and life-limiting diagnoses which, in the opinion of the Investigator, would make completion of the protocol unlikely. A participant assigned female at birth is eligible to participate if they are postmenopausal or not a person of childbearing potential. Key Exclusion Criteria: Close contact with someone with laboratory-confirmed influenza and/or RSV infection or with someone who has been treated with antiviral therapies for influenza (for example, Tamiflu®) within the past 5 days prior to Day 1. Reported history of congenital or acquired immunodeficiency, immunosuppressive condition or immune-mediated disease, asplenia, or recurrent severe infections. Participant has tested positive for influenza or RSV by local health authority-approved testing methods ≤6 months prior to Day 1. Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to study injections (Day 1 and Day 22) or plans to receive a vaccine authorized or approved by a local health agency within 28 days after study injections. Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine ≤6 months prior to Day 1. Participant has received any RSV vaccine (authorized/approved by local health agency or investigational) prior to Day 1. Note: Other protocol-defined inclusion and/or exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 65 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzone HD + mRNA-1345<br>Participants will receive Fluzone HD + mRNA-1345 by intramuscular (IM) injection on Day 1 followed by placebo by IM injection on Day 22. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>Biological: mRNA-1345<br>* Suspension for injection<br>Biological: Fluzone HD<br>* Suspension for injection<br>|
| Experimental: Fluzone HD Followed by mRNA-1345<br>Participants will receive Fluzone HD + placebo by IM injection on Day 1 followed by mRNA-1345 by IM injection on Day 22. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>Biological: mRNA-1345<br>* Suspension for injection<br>Biological: Fluzone HD<br>* Suspension for injection<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 Adverse Reactions (ARs) |  | 7 days after each injection | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | 21 days after each injection | 
| Number of Participants With Medically Attended AEs (MAAEs) |  | Day 1 through end of study (EOS; Day 202) | 
| Number of Participants With Adverse Events of Special Interest (AESIs) |  | Day 1 through EOS (Day 202) | 
| Number of Participants With Serious Adverse Events (SAEs) |  | Day 1 through EOS (Day 202) | 
| Number of Participants With AEs Leading to Discontinuation |  | Day 1 through EOS (Day 202) | 
| Geometric Mean Titer (GMT) of Serum RSV-A and RSV-B Neutralizing Antibodies (Abs) |  | Day 22 (for Arm 1) and Day 43 (for Arm 2) | 
| GMT of Serum Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza |  | Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroresponse in RSV-A Neutralizing Abs From Baseline to Day 22 (for Arm 1) or Day 43 (for Arm 2) | Seroresponse is defined as postvaccination titers ≥4× lower limit of quantification (LLOQ) if baseline is <LLOQ or a ≥4-fold increase from baseline if baseline is ≥LLOQ. | Baseline to Day 22 (for Arm 1) or 43 (for Arm 2) | 
| Geometric Mean Fold Rise (GMFR) of Postbaseline/Baseline Serum RSV-A and RSV-B Neutralizing Abs |  | Baseline to Day 22 (for Arm 1) or 43 (for Arm 2) | 
| Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B Neutralizing Ab Titers at Day 22 (for Arm 1) or Day 43 (for Arm 2) |  | Baseline to Day 22 (for Arm 1) or 43 (for Arm 2) | 
| Percentage of Participants with Seroconversion as Measured by HAI Assay | Seroconversion is defined as postvaccination titer ≥1:40 if baseline is <1:10 or a ≥4-fold rise in postvaccination HAI Ab titer if baseline is ≥1:10. | Baseline to Day 22 | 
| GMFR of Serum Ab Level, as Measured by HAI Assay |  | Baseline to Day 22 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Viral Diseases, Messenger RNA, Moderna, mRNA-1345, Respiratory syncytial virus, Vaccines, RSV Vaccine