A Study to Evaluate the Safety and Efficacy of mRNA-1345 Vaccine Targeting Respiratory Syncytial Virus (RSV) in Adults ≥60 Years of Age

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to evaluate the safety and tolerability of mRNA-1345 vaccine and to demonstrate the efficacy of a single dose of mRNA-1345 vaccine in the prevention of a first episode of RSV-associated lower respiratory tract disease (RSV-LRTD) as compared with placebo from 14 days postinjection through 12 months.

Detailed Description
-----------------
The study will be conducted in 2 phases: Phase 2 and Phase 3. In the Phase 2 segment, up to 2,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio. In the Phase 3 segment, approximately 35,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio.

Official Title
-----------------
A Phase 2/3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus (RSV), in Adults ≥60 Years of Age

Conditions
-----------------
Respiratory Syncytial Virus

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: mRNA-1345


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Adults ≥ 60 years of age who are primarily responsible for self-care and activities of daily living. Participants may have one or more chronic medical diagnoses (including chronic heart failure [CHF] and chronic obstructive pulmonary disease [COPD]), but should be medically stable Body mass index from ≥18 kilograms (kg)/square meter (m^2) to ≤35 kg/m^2 Key Exclusion Criteria: Participation in another clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of the Day 1 study injection. Current participation in research involving receipt of any investigational RSV product History of a serious reaction to any prior vaccination or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization. Received or plans to receive any non-study vaccine within 28 days before or after the Day 1 study injection. Other inclusion and/or exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1345<br>Single injection of mRNA-1345 on Day 1. | Drug: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: Placebo<br>Single injection of mRNA-1345 matching-placebo on Day 1. | Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) up to 7 Days Postinjection |  | Up to 7 days postinjection | 
| Number of Participants with Unsolicited Adverse Events (AEs) up to 28 Days Postinjection |  | Up to 28 days postinjection | 
| Number of Participants With Medically Attended AEs (MAAEs), Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Withdrawal up to 24 Months Postinjection |  | Up to 24 months postinjection | 
| Vaccine Efficacy (VE) of mRNA-1345 to Prevent a First Episode of RSV-LRTD with 2 or More Symptoms within the Period of 14 Days Postinjection up to 12 Months Postinjection | VE of mRNA-1345 to prevent reverse transcription polymerase chain reaction (RT-PCR) confirmed protocol-defined RSV-LRTD, defined as 100*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo). | 14 days postinjection up to 12 months postinjection | 
| VE of mRNA-1345 to Prevent a First Episode of RSV-LRTD with 3 or More Symptoms within the Period of 14 Days Postinjection up to 12 Months Postinjection | VE of mRNA-1345 to prevent reverse transcription polymerase chain reaction (RT-PCR) confirmed protocol-defined RSV-LRTD, defined as 100*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo). | 14 days postinjection up to 12 months postinjection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VE of mRNA-1345 to Prevent a First Episode of RSV-Associated Acute Respiratory Disease (RSV-ARD) within the Period of 14 Days Postinjection up to 12 Months Postinjection | VE of mRNA-1345 to prevent RT-PCR confirmed protocol-defined RSV-ARD, defined as 100*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo). | 14 days postinjection up to 12 months postinjection | 
| VE of mRNA-1345 to Prevent First Hospitalization Associated with RSV-ARD or RSV-LRTD within the Period of 14 Days Postinjection up to 12 Months Postinjection | VE of mRNA-1345 to prevent first hospitalization associated with RSV-ARD or RSV-LRTD, defined as 100*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo). | 14 days postinjection up to 12 months postinjection | 
| Geometric Mean Titer (GMT) of Serum RSV Neutralizing Antibodies (Abs) |  | Baseline through up to 24 months postinjection | 
| Geometric Mean Concentration (GMC) of Serum RSV Binding Abs |  | Baseline through up to 24 months postinjection | 
| Seroresponse Rate in RSV Neutralizing Abs |  | Baseline through up to 24 months postinjection | 
| Geometric Mean Fold-Rise of Postbaseline/Baseline Ab Titers |  | Baseline through up to 24 months postinjection | 
| Proportion of Participants with ≥4-fold Increases in Ab Titers from Baseline |  | Baseline through up to 24 months postinjection | 

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