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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
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.
Time frame: Day 373 through Day 466
Number of Participants With Solicited Local and Systemic Adverse Reactions
Time frame: Up to Day 64 (7 days after the last study injection)
Number of Participants With Unsolicited Adverse Events
Time frame: Up to Day 87 (28 days after the last study injection)
Number of Participants With Medically Attended Adverse Events
Time frame: Up to Day 237 (6 months after the last study injection)
Number of Participants With Serious Adverse Events
Time frame: Day 1 through Day 542
Number of Participants With Adverse Events of Special Interest
Time frame: Day 1 through Day 542
Number of Participants With Adverse Events Leading to Discontinuation
Time frame: Day 1 through Day 542
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.
Time frame: Day 373 through Day 466
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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.
Time frame: 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.
Time frame: Day 373 through Day 466
Post-transplant: Duration of anti-CMV Antiviral Therapy
Time frame: Day 373 through Day 466
Post-transplant: Time to Initiation of anti-CMV Antiviral Therapy
Time frame: Day 373 through Day 466
Post-transplant: Number of Participants Requiring anti-CMV Antiviral Therapy
Time frame: 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.
Time frame: 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.
Time frame: Day 380 through Day 466
Post-transplant: Time to Onset of Initial CMV Viremia
Time frame: Day 373 through Day 466
Post-transplant: Duration of Initial CMV Viremia
Time frame: 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.
Time frame: 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
Time frame: Day 373 through Day 466
Post-transplant: Peak Viral Load in Participants with CMV Viremia
Time frame: Day 373 through Day 466
Post-transplant: CMV Viremia Area Under the Curve
Time frame: 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.
Time frame: 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.
Time frame: Day 365 through Day 466
Post-transplant: Number of Participants Requiring Liver Re-transplantation
Time frame: Day 365 through Day 542
Post-transplant: All-cause Mortality
Time frame: 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.
Time frame: Day 365 through Day 542
Pre-transplant: Titer of CMV- Specific Neutralizing Antibody (nAb) as Measured by Cell-based Neutralization Assay
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542