A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Allogenic Hematopoietic Cell Transplantation (HCT) Participants.
Phase 2
Recruiting
- Conditions
- Cytomegalovirus Infection
- Interventions
- Biological: Placebo
- Registration Number
- NCT05683457
- Lead Sponsor
- ModernaTX, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 224
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description mRNA-1647 mRNA-1647 Participants will receive mRNA-1647 by intramuscular (IM) injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180. Placebo Placebo Participants will receive mRNA-1647 matching placebo by IM injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180.
- Primary Outcome Measures
Name Time Method 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 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 Grade ≥3 Acute Graft-Versus-Host Disease (GVHD) Up to Day 365
- Secondary Outcome Measures
Name Time Method 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 Day 100 to Month 9 CMV Viremia is defined as ≥300 international units/milliliters (IU/mL).
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 Post-HCT. 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
Trial Locations
- Locations (1)
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States