A Study to Investigate the Immunogenicity and Safety of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in High-risk Adults

Study Overview
=================
Brief Summary
-----------------
The study is divided into 2 parts (Part A and Part B). Part A of the study will evaluate the safety and immune response to mRNA-1345 in high-risk adults aged ≥18 to <60 years. Part B of the study will evaluate the safety and immune response to mRNA-1345 in adults who received solid organ transplant (SOT).

Official Title
-----------------
A Phase 3 Study to Evaluate the Immunogenicity and Safety of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in High-Risk Adults

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

Intervention / Treatment
-----------------
* Biological: mRNA-1345


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Part A: Adults ≥18 to <60 years of age at the time of consent who are primarily responsible for self-care and activities of daily living. Documented confirmation by a physician of the diagnosis of at least one of the following conditions: Coronary artery disease and/or congestive heart failure. Chronic lung disease (for example, including but not limited to chronic obstructive pulmonary disease or persistent asthma). Stable type 1 or type 2 diabetes mellitus controlled with at least 1 medication started 90 days or more prior to Day 1. Part B: Adults ≥18 years of age at the time of consent who are primarily responsible for self-care and activities of daily living. Recipient of an SOT (kidney, liver, or lung transplant) ≥180 days prior to day of consent and receiving chronic immunosuppressive therapy for the prevention of allograft rejection. Parts A and B: - Able to comply with study requirements. Key Exclusion Criteria: Part A: Participation in an another clinical research trial where the participant has received an investigational product 180 days prior to Day 1. Participation in an RSV trial at any time prior to Day 1 is exclusionary. History of a diagnosis or condition, that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of the mRNA-1345 injection or any components of the mRNA-1345 injection. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 180 days prior to Day 1. History of myocarditis, pericarditis, or myopericarditis. Part B: Previous treatment with alemtuzumab or rituximab within 2 years prior to Day 1. Previous treatment with plasmapheresis within 30 days prior to Day 1. A history of complications of immunosuppression. A history of biopsy proven or clinically diagnosed rejection within 90 days prior to Day 1 or suspected active chronic rejection according to the Investigator's judgment. Note: Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part A participants will be randomized into 2 treatment dose groups at a 1:1 ratio. Part B is non-randomized.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: mRNA-1345 Dose 1<br>Single injection of mRNA-1345 administered intramuscularly (IM) on Day 1. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1345 Dose 2<br>Single injection of mRNA-1345 administered IM on Day 1. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1345 Dose 2<br>Two injections of mRNA-1345 administered IM on Day 1 and Day 57. | Biological: mRNA-1345<br>* Sterile liquid for 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) |  | Day 1 through Day 7 (7 days post injection) for Part A and Day 1 through Day 64 (7 days post second injection) for Part B | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Day 1 through Day 28 (28 days post injection) for Part A and Day 1 through Day 84 (28 days post second injection) for Part B | 
| Number of Participants With Medically Attended AEs (MAAEs) |  | Day 1 through Month 6 (for Part A) and Day 1 through Month 9 (for Part B) | 
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and AEs Leading to Discontinuation |  | Day 1 through End of Study (Day 730) | 
| Part A: Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) and Respiratory Syncytial Virus Subtype B (RSV-B) Neutralizing Antibodies (Abs) at Day 29 |  | Day 29 | 
| Part B: GMT of Serum RSV-A and RSV-B Neutralizing Abs at Day 85 |  | Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Seroresponse Rate (SRR) of RSV-A and RSV-B Neutralizing Abs on Day 29 |  | Day 29 | 
| Part A: GMT of Serum RSV-A and RSV-B Neutralizing Abs at Day 29 |  | Day 29 | 
| Part A: GMT of Postinjection/Baseline Titers to RSV-A and RSV-B Neutralizing Abs |  | Up to Day 730 | 
| Part A: Geometric Mean Fold Rise (GMFR) of Postinjection/Baseline Titers to RSV-A and RSV-B Neutralizing Abs |  | Up to Day 730 | 
| Part A: SRR of Serum RSV-A and RSV-B Neutralizing Abs up to Day 730 |  | Up to Day 730 | 
| Part A: Number of Participants with ≥2-Fold Increase in RSV-A and RSV-B Neutralizing Abs Titers up to Day 730 |  | Up to Day 730 | 
| Part B: GMT of Serum RSV-A and RSV-B Neutralizing Abs at Day 29 |  | Day 29 | 
| Part B: SRR of Serum RSV-A and RSV-B Neutralizing Abs on Day 29 |  | Day 29 | 
| Part B: SRR of Serum RSV-A and RSV-B Neutralizing Abs on Day 85 |  | Day 85 | 

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