A Study of mRNA-1647 Cytomegalovirus Vaccine in Liver Transplant Candidates and Recipients

A Phase 2, Observer-Blind, Placebo-Controlled, Proof-of-Concept Trial to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus Vaccine in Liver Transplant Candidates and Recipients

The purpose of this study is to assess the effect of pre-transplant mRNA-1647 on post-transplant cytomegalovirus (CMV) virologic outcomes, anti-CMV antiviral use, and clinical outcomes in CMV-seropositive and CMV-seronegative liver transplant candidates who receive transplants and to assess the safety, reactogenicity, and immunogenicity of mRNA-1647 in all participants.

Study Overview

• Status: Withdrawn
• Conditions: Cytomegalovirus Infection
• Intervention / Treatment: Biological: Placebo; Biological: mRNA-1647

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-8344
      • Not yet recruiting
      • UCLA Health - Westwood
    • San Francisco, California, United States, 94143-2202
      • Not yet recruiting
      • UCSF - Infectious Disease Clinic
    • Stanford, California, United States, 94305
      • Not yet recruiting
      • Stanford University
  • Florida
    • Miami, Florida, United States, 33136-1101
      • Not yet recruiting
      • University of Miami, Jackson Memorial Hospital
    • Tampa, Florida, United States, 33606-2707
      • Not yet recruiting
      • Tampa General Medical Group
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30309
      • Not yet recruiting
      • Piedmont Transplant Institute
  • Illinois
    • Chicago, Illinois, United States, 60611-2945
      • Not yet recruiting
      • Northwestern University, Feinberg School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Not yet recruiting
      • University of Kentucky Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-2600
      • Not yet recruiting
      • Tulane University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201-1009
      • Not yet recruiting
      • University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21287-0020
      • Not yet recruiting
      • Johns Hopkins Hospital
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655-0002
      • Recruiting
      • University of Massachusetts Medical School
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Not yet recruiting
      • Henry Ford Health System
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Not yet recruiting
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10032-3720
      • Not yet recruiting
      • Columbia University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207-1248
      • Not yet recruiting
      • Carolinas Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267-2827
      • Not yet recruiting
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • University of Pennsylvania School of medicine
  • Washington
    • Seattle, Washington, United States, 98104
      • Not yet recruiting
      • Swedish Medical Center
    • Seattle, Washington, United States, 98195-0001
      • Not yet recruiting
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Not yet recruiting
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Having a negative (that is, CMV-seronegative) or a positive (that is, CMV-seropositive) result using a blood IgG assay performed at the central laboratory or a previously documented seropositive result.
• Listed and anticipated to receive their first deceased donor or living donor liver transplant within 2 months to 12 months of enrollment.
• A person of nonchildbearing potential, as defined in the protocol.
• For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection, and agreement to continue adequate contraception or abstinence through 3 months following last study injection.

Exclusion Criteria:

• Listed as "status 1A" for liver transplant.
• Hypersensitivity to acyclovir, ganciclovir, or valganciclovir.
• Previous receipt of a solid organ or hematopoietic transplant.
• Listed for or anticipated to receive an organ transplant other than liver, either simultaneously or sequentially.
• 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, including mRNA-1647, or its excipients.
• Human immunodeficiency virus (HIV) infection (based on documented testing performed during the transplant evaluation process and no clinical suspicion of HIV infection).
• Prior (ever) receipt of a stem cell transplant (peripheral blood stem cell, marrow, cord blood).
• Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results.

Note: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mRNA-1647; CMV-seronegative and CMV-seropositive participants will receive 3 intramuscular (IM) injections of mRNA-1647 vaccine on Days 1, 29, and 57.	Biological: mRNA-1647; Sterile liquid for injection
Experimental: Placebo; CMV-seronegative and CMV-seropositive participants will receive 3 IM injections of mRNA-1647 vaccine-matching placebo on Days 1, 29, and 57.	Biological: Placebo; Sterile liquid for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-transplant: Time to the First Occurrence of a Clinically Significant Cytomegalovirus Infection (CS-CMVi) In Seropositive Participants	CS-CMVi will be defined as CMV viremia necessitating treatment (with treatment initiated at viral load ≥250 international units/milliliter [IU/mL] and/or CMV disease) through Day 466.	Day 373 through Day 466
Number of Participants With Solicited Local and Systemic Adverse Reactions		Up to Day 64 (7 days after the last study injection)
Number of Participants With Unsolicited Adverse Events		Up to Day 87 (28 days after the last study injection)
Number of Participants With Medically Attended Adverse Events		Up to Day 237 (6 months after the last study injection)
Number of Participants With Serious Adverse Events		Day 1 through Day 542
Number of Participants With Adverse Events of Special Interest		Day 1 through Day 542
Number of Participants With Adverse Events Leading to Discontinuation		Day 1 through Day 542

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-transplant: Time to First Occurrence of Adjudicated CMV Disease in Seronegative Participants Who Receive a Liver Transplant from a CMV-seropositive Donor	Evidence of adjudicated CMV disease and/or infection, as defined in the protocol, will include signs, symptoms, and biopsy evidence.	Day 373 through Day 466
Post-transplant: Number of Seronegative Participants Who Received a Liver Transplant from a CMV-seropositive Donor with Any Occurrence of CMV Viremia	Viremia will be defined as any detectable viral load through Day 466.	Day 373 through Day 466
Post-transplant: Number of Seronegative Participants Who Received a Liver Transplant from a CMV-seropositive Donor with an Occurrence of CMV Viremia	Viremia will be defined as a viral load ≥1000 IU/mL through Day 466.	Day 373 through Day 466
Post-transplant: Duration of anti-CMV Antiviral Therapy		Day 373 through Day 466
Post-transplant: Time to Initiation of anti-CMV Antiviral Therapy		Day 373 through Day 466
Post-transplant: Number of Participants Requiring anti-CMV Antiviral Therapy		Day 373 through Day 466
Number of Participants With Investigator-reported CMV Disease	Evidence of CMV disease and/or infection, as defined in the protocol, will include signs, symptoms, and biopsy evidence.	Day 380 through Day 466
Number of Seropositive Participants With CMV Disease, Defined as Adjudicated CMV Disease	Evidence of adjudicated CMV disease and/or infection, as defined in the protocol, will include signs, symptoms, and biopsy evidence. Adjudication will occur by a blinded adjudication committee per protocol.	Day 380 through Day 466
Post-transplant: Time to Onset of Initial CMV Viremia		Day 373 through Day 466
Post-transplant: Duration of Initial CMV Viremia		Day 373 through Day 466
Post-transplant: Number of Participants With Recurrent CMV Viremia Following 2 Consecutive Undetectable CMV Viral Load Assays	Recurrent CMV viremia will be defined as a viral load ≥250 IU/mL for seropositive participants and any detectable level for seronegative participants who receive a seropositive organ.	Day 373 through Day 466
Post-transplant: Duration of Recurrent CMV Viremia	Recurrent CMV viremia will be defined as a viral load ≥250 IU/mL for seropositive participants and any detectable level for seronegative participants who receive a seropositive organ	Day 373 through Day 466
Post-transplant: Peak Viral Load in Participants with CMV Viremia		Day 373 through Day 466
Post-transplant: CMV Viremia Area Under the Curve		Day 373 through Day 466
Post-transplant: Number of Participants With Neutropenia	Neutropenia will be defined as an absolute neutrophil count ≤500 absolute neutrophils/microliter.	Day 373 through Day 466
Post-transplant: Number of Participants With Leukopenia on 2 Successive Measurements Separated by at Least 24 Hours	Leukopenia will be defined as an absolute white blood cells (WBC) <3500 cells/cubic milliliter (mm^3) if baseline was ≥4000 cells/mm^3 or a decrease in WBC of >20% if the baseline count was <4000 cells/mm^3.	Day 365 through Day 466
Post-transplant: Number of Participants Requiring Liver Re-transplantation		Day 365 through Day 542
Post-transplant: All-cause Mortality		Day 365 through Day 542
Post-transplant: Number of Participants with Biopsy Proven Allograft Rejection	Biopsy proven allograft rejection will be adjudicated by a blinded adjudication committee per protocol.	Day 365 through Day 542
Pre-transplant: Titer of CMV- Specific Neutralizing Antibody (nAb) as Measured by Cell-based Neutralization Assay		Day 1, Day 29, Day 57, Day 87, Day 237, and Day 365
Post-transplant: Titer of CMV-Specific nAb Post-transplant as Measured by Cell-based Neutralization Assay		Day 365, Day 466, and Day 542
Pre- and Post-transplant: Geometric Mean Titer (GMT) of Anti-glycoprotein B (gB)-specific Immunoglobulin G (IgG) and Antipentamer-specific IgG as Measured by Enzyme-linked Immunosorbent Assay (ELISA)		Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542
Pre- and Post-transplant: Geometric Mean Concentration (GMC) of Anti-gB-specific IgG and Antipentamer-specific IgG as Measured by ELISA		Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542
Pre- and Post-transplant: Geometric Mean Ratio (GMR) of Post-baseline/Baseline GMTs and GMCs		Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542
Pre- and Post-transplant: Geometric Mean Fold Rise (GMFR) of Post-baseline/Baseline GMTs or GMCs		Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2024
• Primary Completion (Estimated): February 14, 2027
• Study Completion (Estimated): December 14, 2027

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Vaccine; mRNA-1647; Cytomegalovirus; CMV; Cytomegalovirus Vaccine; Cytomegalovirus Infections; Infection Viral; Messenger RNA; DNA Virus Infections; Liver Transplant; Cytomegalovirus Disease; Human Herpesvirus; Virus Disease
• Additional Relevant MeSH Terms: Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Infections; Cytomegalovirus Infections
• Other Study ID Numbers: mRNA-1647-P206

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No