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

Phase 2
Withdrawn
Conditions
Cytomegalovirus Infection
Interventions
Biological: mRNA-1647
Biological: Placebo
Registration Number
NCT06133010
Lead Sponsor
ModernaTX, Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
mRNA-1647mRNA-1647CMV-seronegative and CMV-seropositive participants will receive 3 intramuscular (IM) injections of mRNA-1647 vaccine on Days 1, 29, and 57.
PlaceboPlaceboCMV-seronegative and CMV-seropositive participants will receive 3 IM injections of mRNA-1647 vaccine-matching placebo on Days 1, 29, and 57.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Medically Attended Adverse EventsUp to Day 237 (6 months after the last study injection)
Number of Participants With Adverse Events of Special InterestDay 1 through Day 542
Number of Participants With Adverse Events Leading to DiscontinuationDay 1 through Day 542
Number of Participants With Solicited Local and Systemic Adverse ReactionsUp to Day 64 (7 days after the last study injection)
Number of Participants With Unsolicited Adverse EventsUp to Day 87 (28 days after the last study injection)
Post-transplant: Time to the First Occurrence of a Clinically Significant Cytomegalovirus Infection (CS-CMVi) In Seropositive ParticipantsDay 373 through Day 466

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.

Number of Participants With Serious Adverse EventsDay 1 through Day 542
Secondary Outcome Measures
NameTimeMethod
Post-transplant: All-cause MortalityDay 365 through Day 542
Post-transplant: Number of Seronegative Participants Who Received a Liver Transplant from a CMV-seropositive Donor with Any Occurrence of CMV ViremiaDay 373 through Day 466

Viremia will be defined as any detectable viral load through Day 466.

Post-transplant: Time to Onset of Initial CMV ViremiaDay 373 through Day 466
Post-transplant: Number of Participants with Biopsy Proven Allograft RejectionDay 365 through Day 542

Biopsy proven allograft rejection will be adjudicated by a blinded adjudication committee per protocol.

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
Post-transplant: Time to Initiation of anti-CMV Antiviral TherapyDay 373 through Day 466
Post-transplant: Peak Viral Load in Participants with CMV ViremiaDay 373 through Day 466
Post-transplant: Number of Participants With NeutropeniaDay 373 through Day 466

Neutropenia will be defined as an absolute neutrophil count ≤500 absolute neutrophils/microliter.

Post-transplant: Time to First Occurrence of Adjudicated CMV Disease in Seronegative Participants Who Receive a Liver Transplant from a CMV-seropositive DonorDay 373 through Day 466

Evidence of adjudicated CMV disease and/or infection, as defined in the protocol, will include signs, symptoms, and biopsy evidence.

Post-transplant: Number of Seronegative Participants Who Received a Liver Transplant from a CMV-seropositive Donor with an Occurrence of CMV ViremiaDay 373 through Day 466

Viremia will be defined as a viral load ≥1000 IU/mL through Day 466.

Post-transplant: Duration of anti-CMV Antiviral TherapyDay 373 through Day 466
Post-transplant: Number of Participants Requiring anti-CMV Antiviral TherapyDay 373 through Day 466
Number of Participants With Investigator-reported CMV DiseaseDay 380 through Day 466

Evidence of CMV disease and/or infection, as defined in the protocol, will include signs, symptoms, and biopsy evidence.

Number of Seropositive Participants With CMV Disease, Defined as Adjudicated CMV DiseaseDay 380 through Day 466

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.

Post-transplant: Duration of Initial CMV ViremiaDay 373 through Day 466
Post-transplant: Duration of Recurrent CMV ViremiaDay 373 through Day 466

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

Post-transplant: CMV Viremia Area Under the CurveDay 373 through Day 466
Post-transplant: Number of Participants With Leukopenia on 2 Successive Measurements Separated by at Least 24 HoursDay 365 through Day 466

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.

Post-transplant: Number of Participants Requiring Liver Re-transplantationDay 365 through Day 542
Pre-transplant: Titer of CMV- Specific Neutralizing Antibody (nAb) as Measured by Cell-based Neutralization AssayDay 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 AssayDay 365, Day 466, and Day 542
Post-transplant: Number of Participants With Recurrent CMV Viremia Following 2 Consecutive Undetectable CMV Viral Load AssaysDay 373 through Day 466

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.

Pre- and Post-transplant: Geometric Mean Concentration (GMC) of Anti-gB-specific IgG and Antipentamer-specific IgG as Measured by ELISADay 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 GMCsDay 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 GMCsDay 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542
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