Cytomegalovirus Infection
Conditions
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
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.
Interventions
BIOLOGICALmRNA-1647
Lyophilized product that is reconstituted with 0.9% sodium chloride (normal saline).
BIOLOGICALPlacebo
0.9% sodium chloride (normal saline) injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
United States
Contacts
CONTACTModerna WeCare Team
Outcome results
None listed