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

Cytomegalovirus Infection Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05683457
• Other study ID #: mRNA-1647-P205
• Status: Recruiting
• Phase: Phase 2
• Start date: April 5, 2023
• Est. completion date: August 1, 2025

Study information

• Verified date: March 2024
• Source: ModernaTX, Inc.
• Contact: Moderna Clinical Trials Support Center
• Phone: 1-877-777-7187
• Email: clinicaltrials[@]modernatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 224
• Est. completion date: August 1, 2025
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cytomegalovirus Infection
• Cytomegalovirus Infections
• Infections

Intervention

Biological:
• mRNA-1647
Lyophilized product that is reconstituted with 0.9% sodium chloride (normal saline).
• Placebo
0.9% sodium chloride (normal saline) injection

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
ModernaTX, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to the First Occurrence of an CS-CMVi Event as Measured by initiation of anti-CMV Antiviral Therapy		Day 100 to Month 9
Primary	Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)		Up to Day 187 (7 days after last study injection)
Primary	Number of Unsolicited Adverse Events (AEs)		Up to Day 205 (25 days after last study injection)
Primary	Number of Participants with Severe AEs		Up to Day 365
Primary	Number of Participants with Serious Adverse Events (SAEs)		Up to Day 365
Primary	Number of Participants with Grade =3 Acute Graft-Versus-Host Disease (GVHD)		Up to Day 365
Secondary	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
Secondary	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
Secondary	Number of Participants with CMV End-Organ Disease		Day 100 to Month 9
Secondary	Duration of CMV Viremia		Day 100 to Month 9
Secondary	Duration of CMV Treatment		Day 100 to Month 9
Secondary	Number of Participants with Non-Relapse Mortality at 9 Months PostHCT.		Month 9
Secondary	Titer of CMV-Specific Neutralizing Antibody (nAb)		Days 42, 67, 92, 117, 180, 205 and 270
Secondary	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
Secondary	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
Secondary	Geometric Mean Fold Rise (GMFR) of Postbaseline/Baseline GMTs or GMCs		Days 42, 67, 92, 117, 180, 205 and 270