A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Participants 16 to 40 Years of Age

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to evaluate the efficacy of mRNA 1647 vaccine in CMV-seronegative female participants and to evaluate the safety and reactogenicity of mRNA-1647 vaccine in all participants.

Official Title
-----------------
A Phase 3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Participants 16 to 40 Years of Age

Conditions
-----------------
Cytomegalovirus Infection

Intervention / Treatment
-----------------
* Biological: mRNA-1647
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Participants aged ≥20 years, has or anticipates having direct exposure within 7 months after the planned first dose (in the home, socially, or occupationally) to at least 1 child ≤5 years of age. Direct exposure is defined as either participant is the parent, or participant has close contact (feeding, diaper changes, childcare/supervision) for at least 8 hours per week. CMV-seronegative Cohort is CMV-seronegative based on CMV testing at Screening. CMV-seropositive Cohort is CMV-seropositive based on CMV testing at Screening. Investigator assessment confirms that the participant (including in the case of an emancipated minor), or parent(s)/legally acceptable representative (LAR)(s), as applicable, understand and are willing and physically able to comply with protocol-mandated follow-up including all study visits and procedures anticipated during the 30 month study period. Female participants of child-bearing potential: Urine pregnancy test is negative at Screening and negative on the day of the first injection (Day 1). If the participant is sexually active with men, has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1) and agrees to continue adequate contraception through 3 months following the third study injection (Month 9/Day 257). Key Exclusion Criteria: 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. Received or plans to receive any nonstudy vaccine <28 days prior to and after any study injection; in addition, the following criteria for COVID-19 and influenza vaccines apply: Any COVID-19 primary vaccination series must have been completed a minimum 28 days prior to receiving any dose of the study injection. COVID-19 vaccines (including any booster dose, regardless of manufacturer) must be administered at least 28 days prior to or after any study injection. Influenza vaccines may be administered > 14 days prior to or after any study injection. Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to the day of first injection (Day 1) (for corticosteroids, ≥5 milligrams (mg)/day of prednisone equivalent) or plans to do so during the course of the study. Inhaled, nasal, and topical steroids are allowed. Stable immunomodulator regimens used for managing environmental allergies are allowed. Receipt of an antiviral with activity against CMV (ganciclovir, valganciclovir, foscarnet, cidofovir, letermovir, acyclovir, valacyclovir) <2 weeks prior to the day of first injection or plans to do so during the course of the study. Previous receipt of an investigational CMV vaccine. Receipt of systemic immunoglobulins or blood products <3 months prior to the day of first injection. Participated in an interventional clinical study <28 days prior to the day of first injection (Day 1) or plans to do so while enrolled in this study. Participant has donated ≥450 milliliters (mL) of blood products <28 days prior to Screening. Participant is a member of study team or is an immediate family member or household member of study personnel.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

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-1647<br>Participants will receive mRNA-1647 vaccine by intramuscular (IM) injection on Day 1, Day 57, and Day 169. | Biological: mRNA-1647<br>* Lyophilized product that is reconstituted with 0.9% sodium chloride (normal saline)<br>|
| Placebo Comparator: Placebo<br>Participants will receive mRNA-1647 vaccine matching placebo by IM injection on Day 1, Day 57, and Day 169. | 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 |
| --- | --- | --- |
| Seroconversion From a Negative to a Positive Result for Serum Immunoglobulin G (IgG) Against Antigens not Encoded by mRNA-1647 |  | Day 197 (28 days after the third injection) up to Day 887 (24 months after the third injection) | 
| Number of Participants With Solicited Adverse Reactions (ARs) |  | Up to 176 days (7 days after each injection) | 
| Number of Participants With Unsolicited Adverse Events (AEs) |  | Up to 197 days (28 days after each injection) | 
| Number of Participants With Medically-Attended Adverse Events (MAAEs) |  | Day 1 through 6 months after the last injection (up to 347 days) | 
| Number of Participants With Adverse Event of Special Interests (AESIs) and Serious Adverse Events (SAEs) |  | Day 1 through end of study (up to Day 887) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Antigen-Specific Neutralizing Antibody (nAb) and Binding Antibody |  | Day 1, Months 3, 7, 12, 18, 24, and 30 | 
| Geometric Mean Concentration (GMC) of Antigen-Specific Neutralizing Antibody (nAb) and Binding Antibody |  | Day 1, Months 3, 7, 12, 18, 24, and 30 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mRNA-1647, Moderna, Cytomegalovirus, CMV, Cytomegalovirus Vaccine, Cytomegalovirus Infections, Cytomegalovirus Congenital, Virus Diseases, Infection Viral, DNA Virus Infections, Messenger RNA