A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Allogenic Hematopoietic Cell Transplantation (HCT) Participants.

Study Overview
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Brief Summary
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The main purpose of the study is to evaluate the efficacy and safety of mRNA-1647 compared to placebo to prevent first clinically significant cytomegalovirus infection (CS-CMVi) in the period following cessation of CMV prophylactic treatment (for example, letermovir) on Day 100 postHCT through Month 9 postHCT.

Official Title
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A Phase 2, Observer-Blind, Placebo-Controlled Proof-of-Concept Trial to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus Vaccine in Patients Who Have Undergone Allogeneic Hematopoietic Cell Transplantation (HCT)

Conditions
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Cytomegalovirus Infection

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Receipt of an allogeneic HCT. CMV-seropositive, defined as a documented positive test for anti-CMV IgG. High-risk for CMV: HCT from related, unrelated, or haploidentical donor with post-transplant cyclophosphamide for graft-versus-host-disease (GVHD) prophylaxis; or HCT from related or unrelated donor with at least one mismatch at any of the following human leukocyte antigen (HLA) gene loci (HLA-A, B, C, and DRB1); or HCT from related or unrelated donor with myeloablative conditioning. Persons of nonchildbearing potential or of childbearing potential with negative urine or serum pregnancy test on the day of first vaccination. Persons of childbearing potential who have practiced adequate contraception or have abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose. Persons of childbearing potential who have agreed to continue adequate contraception or abstain from all activities that could result in pregnancy through 3 months following last vaccination. Persons who are not currently breast/chestfeeding. Willingness to comply with study procedures and provide written informed consent. Exclusion Criteria: History of a diagnosis or condition that, in the judgment of the Investigator, may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. A documented positive human immunodeficiency virus (HIV) test. Treatment with alemtuzumab (Campath®), antithymocyte globulin (ATG), or any equivalent in-vivo T cell depleting agent within 12 months. HCT with ex-vivo T cell depletion. Low risk for CMV: HCT from related or unrelated donor with RIC and no other high-risk features. History of prior hematopoietic cell transplantation within 12 months. Receipt of prior investigational CMV vaccines or participation in another CMV therapeutic trial that may interfere with study outcome measures as determined by the Investigator. Suspected or known allergic reaction to any component of any mRNA vaccine or its excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1647<br>Participants will receive mRNA-1647 vaccine by intramuscular (IM) injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180. | 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 42, Day 67, and Day 92, and a booster dose on Day 180. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Occurrence of an CS-CMVi Event as Measured by initiation of anti-CMV Antiviral Therapy |  | Day 100 to Month 9 | 
| Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) |  | Up to Day 187 (7 days after last study injection) | 
| Number of Unsolicited Adverse Events (AEs) |  | Up to Day 205 (25 days after last study injection) | 
| Number of Participants with Severe AEs |  | Up to Day 365 | 
| Number of Participants with Serious Adverse Events (SAEs) |  | Up to Day 365 | 
| Number of Participants with Grade ≥3 Acute Graft-Versus-Host Disease (GVHD) |  | Up to Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with First Occurrence of All CS-CMVi Events as Measured by Initiation of Anti-CMV Antiviral and/or End-Organ Disease |  | Day 100 to Month 9 | 
| Number of Participants with an Occurrence of CMV Viremia | CMV Viremia is defined as ≥300 international units/milliliters (IU/mL). | Day 100 to Month 9 | 
| Number of Participants with CMV End-Organ Disease |  | Day 100 to Month 9 | 
| Duration of CMV Viremia |  | Day 100 to Month 9 | 
| Duration of CMV Treatment |  | Day 100 to Month 9 | 
| Number of Participants with Non-Relapse Mortality at 9 Months PostHCT. |  | Month 9 | 
| Titer of CMV-Specific Neutralizing Antibody (nAb) |  | Days 42, 67, 92, 117, 180, 205 and 270 | 
| Geometric Mean Titer (GMT) of Anti-gB-Specific Immunoglobulin G (IgG) and Anti-Pentamer-Specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) |  | Days 42, 67, 92, 117, 180, 205 and 270 | 
| Geometric Mean Concentration (GMC) of Anti-gB-Specific Immunoglobulin G (IgG) and Anti-Pentamer-Specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) |  | Days 42, 67, 92, 117, 180, 205 and 270 | 
| Geometric Mean Fold Rise (GMFR) of Postbaseline/Baseline GMTs or GMCs |  | Days 42, 67, 92, 117, 180, 205 and 270 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CMV, Human cytomegalovirus, Human Herpesvirus, mRNA-1647, Moderna, Cytomegalovirus Vaccine, Cytomegalovirus Infections, Cytomegalovirus Congenital, Virus Disease, Infection Viral, DNA Virus Infections, Messenger RNA, Hematopoietic cell transplantation