Clinical trial NCT06133010: A Study of mRNA-1647 Cytomegalovirus Vaccine in Liver Transplant Candidates and Recipients
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Cytomegalovirus Infection
Keywords: mRNA-1647
Vaccine
Liver Transplant
CMV
Human Herpesvirus
Cytomegalovirus Vaccine
Cytomegalovirus Infections
Cytomegalovirus Disease
Cytomegalovirus
Virus Disease
Infection Viral
DNA Virus Infections
Messenger RNA
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-15
Enrollment: 0
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Post-transplant: Time to the First Occurrence of a Clinically Significant Cytomegalovirus Infection (CS-CMVi) In Seropositive Participants
timeFrame: Day 373 through Day 466
measure: Number of Participants With Solicited Local and Systemic Adverse Reactions
timeFrame: Up to Day 64 (7 days after the last study injection)
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Up to Day 87 (28 days after the last study injection)
measure: Number of Participants With Medically Attended Adverse Events
timeFrame: Up to Day 237 (6 months after the last study injection)
measure: Number of Participants With Serious Adverse Events
timeFrame: Day 1 through Day 542
measure: Number of Participants With Adverse Events of Special Interest
timeFrame: Day 1 through Day 542
measure: Number of Participants With Adverse Events Leading to Discontinuation
timeFrame: Day 1 through Day 542
Secondary outcomes:
measure: Post-transplant: Time to First Occurrence of Adjudicated CMV Disease in Seronegative Participants Who Receive a Liver Transplant from a CMV-seropositive Donor
timeFrame: Day 373 through Day 466
measure: Post-transplant: Number of Seronegative Participants Who Received a Liver Transplant from a CMV-seropositive Donor with Any Occurrence of CMV Viremia
timeFrame: Day 373 through Day 466
measure: Post-transplant: Number of Seronegative Participants Who Received a Liver Transplant from a CMV-seropositive Donor with an Occurrence of CMV Viremia
timeFrame: Day 373 through Day 466
measure: Post-transplant: Duration of anti-CMV Antiviral Therapy
timeFrame: Day 373 through Day 466
measure: Post-transplant: Time to Initiation of anti-CMV Antiviral Therapy
timeFrame: Day 373 through Day 466
measure: Post-transplant: Number of Participants Requiring anti-CMV Antiviral Therapy
timeFrame: Day 373 through Day 466
measure: Number of Participants With Investigator-reported CMV Disease
timeFrame: Day 380 through Day 466
measure: Number of Seropositive Participants With CMV Disease, Defined as Adjudicated CMV Disease
timeFrame: Day 380 through Day 466
measure: Post-transplant: Time to Onset of Initial CMV Viremia
timeFrame: Day 373 through Day 466
measure: Post-transplant: Duration of Initial CMV Viremia
timeFrame: Day 373 through Day 466
measure: Post-transplant: Number of Participants With Recurrent CMV Viremia Following 2 Consecutive Undetectable CMV Viral Load Assays
timeFrame: Day 373 through Day 466
measure: Post-transplant: Duration of Recurrent CMV Viremia
timeFrame: Day 373 through Day 466
measure: Post-transplant: Peak Viral Load in Participants with CMV Viremia
timeFrame: Day 373 through Day 466
measure: Post-transplant: CMV Viremia Area Under the Curve
timeFrame: Day 373 through Day 466
measure: Post-transplant: Number of Participants With Neutropenia
timeFrame: Day 373 through Day 466
measure: Post-transplant: Number of Participants With Leukopenia on 2 Successive Measurements Separated by at Least 24 Hours
timeFrame: Day 365 through Day 466
measure: Post-transplant: Number of Participants Requiring Liver Re-transplantation
timeFrame: Day 365 through Day 542
measure: Post-transplant: All-cause Mortality
timeFrame: Day 365 through Day 542
measure: Post-transplant: Number of Participants with Biopsy Proven Allograft Rejection
timeFrame: Day 365 through Day 542
measure: Pre-transplant: Titer of CMV- Specific Neutralizing Antibody (nAb) as Measured by Cell-based Neutralization Assay
timeFrame: Day 1, Day 29, Day 57, Day 87, Day 237, and Day 365
measure: Post-transplant: Titer of CMV-Specific nAb Post-transplant as Measured by Cell-based Neutralization Assay
timeFrame: Day 365, Day 466, and Day 542
measure: 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)
timeFrame: Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542
measure: Pre- and Post-transplant: Geometric Mean Concentration (GMC) of Anti-gB-specific IgG and Antipentamer-specific IgG as Measured by ELISA
timeFrame: Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542
measure: Pre- and Post-transplant: Geometric Mean Ratio (GMR) of Post-baseline/Baseline GMTs and GMCs
timeFrame: Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542
measure: Pre- and Post-transplant: Geometric Mean Fold Rise (GMFR) of Post-baseline/Baseline GMTs or GMCs
timeFrame: Day 1, Day 29, Day 57, Day 87, Day 237, Day 365, Day 466, and Day 542
Other outcomes:
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