Clinical trial NCT05683457: A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Allogenic Hematopoietic Cell Transplantation (HCT) Participants.
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cytomegalovirus Infection
Keywords: Human cytomegalovirus
Human Herpesvirus
mRNA-1647
Moderna
CMV
Cytomegalovirus Vaccine
Cytomegalovirus Infections
Cytomegalovirus Congenital
Virus Disease
Infection Viral
DNA Virus Infections
Messenger RNA
Hematopoietic cell transplantation
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-13
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 post-HCT through Month 9 post-HCT.


Eligibility criteria: 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 study injection.
* 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 after last study injection.
* 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 reduced intensity conditioning (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 study 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.

Primary outcomes:
measure: Time to the First Occurrence of an CS-CMVi Event as Measured by initiation of anti-CMV Antiviral Therapy
timeFrame: Day 100 to Month 9
measure: Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
timeFrame: Up to Day 187 (7 days after last study injection)
measure: Number of Unsolicited Adverse Events (AEs)
timeFrame: Up to Day 205 (25 days after last study injection)
measure: Number of Participants with Severe AEs
timeFrame: Up to Day 365
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to Day 365
measure: Number of Participants with Grade ≥3 Acute Graft-Versus-Host Disease (GVHD)
timeFrame: Up to Day 365
Secondary outcomes:
measure: Number of Participants with First Occurrence of All CS-CMVi Events as Measured by Initiation of Anti-CMV Antiviral and/or End-Organ Disease
timeFrame: Day 100 to Month 9
measure: Number of Participants with an Occurrence of CMV Viremia
timeFrame: Day 100 to Month 9
measure: Number of Participants with CMV End-Organ Disease
timeFrame: Day 100 to Month 9
measure: Duration of CMV Viremia
timeFrame: Day 100 to Month 9
measure: Duration of CMV Treatment
timeFrame: Day 100 to Month 9
measure: Number of Participants with Non-Relapse Mortality at 9 Months Post-HCT.
timeFrame: Month 9
measure: Titer of CMV-Specific Neutralizing Antibody (nAb)
timeFrame: Days 42, 67, 92, 117, 180, 205 and 270
measure: Geometric Mean Titer (GMT) of Anti-gB-Specific Immunoglobulin G (IgG) and Anti-Pentamer-Specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)
timeFrame: Days 42, 67, 92, 117, 180, 205 and 270
measure: Geometric Mean Concentration (GMC) of Anti-gB-Specific Immunoglobulin G (IgG) and Anti-Pentamer-Specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)
timeFrame: Days 42, 67, 92, 117, 180, 205 and 270
measure: Geometric Mean Fold Rise (GMFR) of Postbaseline/Baseline GMTs or GMCs
timeFrame: Days 42, 67, 92, 117, 180, 205 and 270
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
References: