A Study of an Epstein-Barr Virus (EBV) Candidate Vaccine, mRNA-1195, in 18- to 55-Year-Old Healthy Adults

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and reactogenicity of mRNA-1195 in healthy adults (18 to 55 years of age).

Detailed Description
-----------------
There will be 2 sequential parts to the study: Participants will be enrolled in Part A of the study first, which will only enroll those participants who are EBV-seropositive at Screening. Part B will enroll only those participants who are EBV-seronegative at Screening.

Official Title
-----------------
A Phase 1, Randomized, Observer-Blind, Placebo-Controlled, 2-Part, Dose-Ranging Study of an EBV Candidate Vaccine, mRNA-1195, in Healthy Adults 18 to 55 Years of Age

Conditions
-----------------
Epstein-Barr Virus Infection

Intervention / Treatment
-----------------
* Biological: mRNA-1195.1
* Biological: mRNA-1195.2
* Biological: mRNA-1189
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: For Part A: Positive EBV serostatus at Screening. For Part B: Negative EBV serostatus at Screening. According to the assessment of the Investigator, is in good general health and can comply with study procedures. For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, and agreement to continue adequate contraception through 3 months following vaccine administration. Key Exclusion Criteria: Participant is acutely ill or febrile (temperature ≥38.0 degrees Celsius [°C]/100.4 degrees Fahrenheit [°F]) 72 hours prior to or at the Screening Visit or Day 1. Symptomatic acute or chronic illness requiring ongoing medical or surgical care, to include changes in medication in the past 2 months indicating that chronic illness/disease is not stable (at the discretion of the Investigator). Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. History of myocarditis, pericarditis, or myopericarditis. Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening Visit (for corticosteroids ≥10 milligrams [mg]/day of prednisone or equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Topical corticosteroids and tacrolimus are allowed. Participant has received or plans to receive any licensed vaccine ≤28 days prior to the first injection (Day 1) or plans to receive a licensed vaccine within 28 days before or after any study injection, with the exception of licensed/authorized influenza or SARS-CoV-2 vaccines, which may be received more than 14 days before or after any study injection. Participant has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study. Note: Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: mRNA-1195.1 Dose Level 1<br>Participants will receive 3 intramuscular (IM) injections of mRNA-1195.1 at Dose Level 1 on Days 1, 57, and 169. | Biological: mRNA-1195.1<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1195.2 Dose Level 1<br>Participants will receive 3 IM injections of mRNA-1195.2 at Dose Level 1 on Days 1, 57, and 169. | Biological: mRNA-1195.2<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1195.1 Dose Level 2<br>Participants will receive 3 IM injections of mRNA-1195.1 at Dose Level 2 on Days 1, 57, and 169. | Biological: mRNA-1195.1<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1195.2 Dose Level 2<br>Participants will receive 3 IM injections of mRNA-1195.2 at Dose Level 2 on Days 1, 57, and 169. | Biological: mRNA-1195.2<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1195.1 Dose Level 3<br>Participants will receive 3 IM injections of mRNA-1195.1 at Dose Level 3 on Days 1, 57, and 169. | Biological: mRNA-1195.1<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1195.2 Dose Level 3<br>Participants will receive 3 IM injections of mRNA-1195.2 at Dose Level 3 on Days 1, 57, and 169. | Biological: mRNA-1195.2<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1195.1 Dose Level 4<br>Participants will receive 3 IM injections of mRNA-1195.1 at Dose Level 4 on Days 1, 57, and 169. | Biological: mRNA-1195.1<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1195.2 Dose Level 4<br>Participants will receive 3 IM injections of mRNA-1195.2 at Dose Level 4 on Days 1, 57, and 169. | Biological: mRNA-1195.2<br>* Sterile liquid for injection<br>|
| Active Comparator: Part A: mRNA-1189<br>Participants will receive 3 IM injections of mRNA-1189 on Days 1, 57, and 169. | Biological: mRNA-1189<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Part A: Placebo<br>Participants will receive IM injection of study drug-matching placebo on Days 1, 57, and 169. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Part B: mRNA-1195.1 or mRNA-1195.2 Low Dose<br>Participants will receive 3 IM injections of mRNA-1195.1 or mRNA-1195.2 (at a dose level selected based on the Part A interim analysis) low dose on Days 1, 57, and 169. | Biological: mRNA-1195.1<br>* Sterile liquid for injection<br>Biological: mRNA-1195.2<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1195.1 or mRNA-1195.2 Middle Dose<br>Participants will receive 3 IM injections of mRNA-1195.1 or mRNA-1195.2 (at a dose level selected based on the Part A interim analysis) middle dose on Days 1, 57, and 169. | Biological: mRNA-1195.1<br>* Sterile liquid for injection<br>Biological: mRNA-1195.2<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1195.1 or mRNA-1195.2 High Dose<br>Participants will receive 3 IM injections of mRNA-1195.1 or mRNA-1195.2 (at a dose level selected based on the Part A interim analysis) high dose on Days 1, 57, and 169. | Biological: mRNA-1195.1<br>* Sterile liquid for injection<br>Biological: mRNA-1195.2<br>* Sterile liquid for injection<br>|
| Active Comparator: Part B: mRNA-1189<br>Participants will receive 3 IM injections of mRNA-1189 on Days 1, 57, and 169. | Biological: mRNA-1189<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Part B: Placebo<br>Participants will receive IM injection of study drug-matching placebo on Days 1, 57, and 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 |
| --- | --- | --- |
| Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) |  | Up to Day 176 | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 197 (28-day follow-up after vaccination) | 
| Number of Participants with Any Serious AEs (SAEs), Medically Attended AEs (MAAEs), AEs Leading to Withdrawal From Study/Discontinuation of Study Vaccine, and AEs of Special Interest (AESIs) |  | Day 1 to end of study (EOS) (Day 337) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of B-Cell Neutralizing Antibody (nAb) and/or Antigen-Specific Binding Antibody (bAb) |  | Days 1, 85, and 197 | 
| Geometric Mean Fold Rise (GMFR) of B-Cell nAb and/or Antigen-Specific bAb |  | Days 1, 85, and 197 | 
| Number of Participants With Seroconversion of B-Cell nAbs and/or Antigen-Specific bAbs |  | Days 1, 85, and 197 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infectious mononucleosis, Mononucleosis, Virus Diseases, Infections, Gamma-herpesvirus