Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1403 and mRNA-1405 to Prevent Norovirus Acute Gastroenteritis in Healthy Adults 18 to 49 Years of Age and 60 to 80 Years of Age.

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1403 and mRNA-1405 in healthy adult participants 18 to 49 years of age and 60 to 80 years of age.

Official Title
-----------------
A Phase 1, Randomized, Placebo-Controlled, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1403 and mRNA-1405, Multivalent Candidate Vaccines to Prevent Norovirus Acute Gastroenteritis in Healthy Adults 18 to 49 Years of Age and 60 to 80 Years of Age

Conditions
-----------------
Norovirus Acute Gastroenteritis

Intervention / Treatment
-----------------
* Biological: mRNA-1403
* Biological: mRNA-1405
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Adults 18 to 49 years of age at the time of consent or adults 60 to 80 years of age at the time of consent. Body mass index of 18 to 39 kilogram/meter^2 (inclusive) at the Screening Visit. Participants assigned female at birth are eligible to participate if they are not pregnant or breast/chest/body feeding. A person of childbearing potential is using a highly effective contraceptive method. Participant has provided written informed consent for participation in this study, Key Exclusion Criteria: Is acutely ill or febrile (temperature ≥38.0°C [100.4°F]) 72 hours prior to or at the Screening Visit or Day 1 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. Has a medical, psychiatric, or occupational condition, including reported history of substance abuse, that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment. Has a current or previous diagnosis of immunosuppressive condition, to include human immunodeficiency virus, or immune-mediated (autoimmune) disease that requires immunosuppressive therapies (drugs or biologics). The use of topical corticosteroids or other immunosuppressive agents (for example, topical calcineurin inhibitor) may be eligible for participation at the discretion of the Investigator. History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine or intervention that includes one or more of the same components contained in the study vaccine. Any history of myocarditis or pericarditis. Coagulopathy or bleeding disorder considered a contraindication to IM injection or phlebotomy. Dermatologic conditions that could affect local solicited AR assessments (for example, tattoos, psoriasis patches affecting skin over the deltoid areas). Has received systemic immunosuppressive therapies (drugs or biologics) for >14 days in total within 6 months prior to Screening (for corticosteroids ≥10 mg/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Inhaled, nasal, intra-articular, and topical steroids are allowed. Has received or plans to receive any licensed/authorized vaccine (to include severe acute respiratory syndrome-related coronavirus-2 vaccine) ≤28 days prior to or within 28 days after each study intervention, with the exception of influenza vaccines, which may be given 14 days before or after receipt of a study intervention. Has received systemic immunoglobulins or blood products within 3 months prior to the Screening Visit or plans for receipt during the study. Has donated ≥450 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 participate in an interventional clinical trial of an investigational vaccine or drug while participating in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1403 Dose Level 1<br>Participants will receive 2 intramuscular (IM) injections of mRNA-1403 at Dose Level 1. | Biological: mRNA-1403<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1403 Dose Level 2<br>Participants will receive 2 IM injections of mRNA-1403 at Dose Level 2. | Biological: mRNA-1403<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1403 Dose Level 3<br>Participants will receive 2 IM injections of mRNA-1403 at Dose Level 3. | Biological: mRNA-1403<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1403 Dose Level 4 Regimen 1<br>Participants will receive 2 IM injections of mRNA-1403 at Dose Level 4. | Biological: mRNA-1403<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1403 Dose Level 4 Regimen 2<br>Participants will receive 1 IM injection of mRNA-1403 at Dose Level 4 and 1 IM injection of study vaccine-matched placebo. | Biological: mRNA-1403<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: mRNA-1405 Dose Level 1<br>Participants will receive 2 IM injections of mRNA-1405 at Dose Level 1. | Biological: mRNA-1405<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1405 Dose Level 2<br>Participants will receive 2 IM injections of mRNA-1405 at Dose Level 2. | Biological: mRNA-1405<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1405 Dose Level 3<br>Participants will receive 2 IM injections of mRNA-1405 at Dose Level 3. | Biological: mRNA-1405<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1405 Dose Level 4 Regimen 1<br>Participants will receive 2 IM injections of mRNA-1405 at Dose Level 4. | Biological: mRNA-1405<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1405 Dose Level 4 Regimen 2<br>Participants will receive 1 IM injections of mRNA-1405 at Dose Level 4 and 1 IM injection of study vaccine-matched placebo. | Biological: mRNA-1405<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Placebo Comparator: Placebo<br>Participants will receive 2 IM injections of study vaccine-matching placebo. | Biological: 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 Reactogenicity Adverse Reactions (ARs) |  | Up to Day 7 after each study intervention | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to 28 days after each vaccination | 
| Number of Participants with Medically Attended AEs (MAAEs) |  | Day 1 through 6 months after last study intervention (Day 169) | 
| Number of Participants with Any SAEs, AEs Leading to Withdrawal From Study/Discontinuation of Study Vaccine, and AESIs |  | Day 1 to end-of study (Day 365) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Histo-Blood Group Antigen (HBGA) Blocking Antibodies Against Vaccine-matched Norovirus (NoV) Genotypes |  | Days 1, 29, and 57 | 
| Geometric Mean Fold Rise (GMFR) of HBGA Blocking Antibodies Titers |  | Days 1, 29, and 57 | 
| Percentage of Participants with Seroresponse Based on HBGA Blocking Antibody Titer |  | Days 29 and 57 | 
| GMT of Binding Antibody (bAb) Against Vaccine-matched NoV Genotypes |  | Days 1, 29, and 57 | 
| GMFR of bAb Titers |  | Days 1, 29, and 57 | 
| Percentage of Participants with Seroresponse Based on bAb Titer |  | Days 29 and 57 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mRNA-1403, mRNA-1405, Norovirus