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

Sponsor

ModernaTX, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06133010

Collaborator

(none)

342

Enrollment

Locations

Arms

47.9

Anticipated Duration (Months)

13.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infection	Biological: mRNA-1647 Biological: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

342 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

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

Anticipated Study Start Date :

Dec 18, 2023

Anticipated Primary Completion Date :

Feb 14, 2027

Anticipated Study Completion Date :

Dec 14, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Post-transplant: Time to the First Occurrence of a Clinically Significant Cytomegalovirus Infection (CS-CMVi) In Seropositive Participants [Day 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 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

Post-transplant: Time to First Occurrence of Adjudicated CMV Disease in Seronegative Participants Who Receive a Liver Transplant from a CMV-seropositive Donor [Day 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 Any Occurrence of CMV Viremia [Day 373 through Day 466]
Viremia will be defined as any detectable viral load 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 [Day 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 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 [Day 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 Disease [Day 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: 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 [Day 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: Duration of Recurrent CMV Viremia [Day 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: 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 [Day 373 through Day 466]
Neutropenia will be defined as an absolute neutrophil count ≤500 absolute neutrophils/microliter.
Post-transplant: Number of Participants With Leukopenia on 2 Successive Measurements Separated by at Least 24 Hours [Day 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-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 [Day 365 through Day 542]
Biopsy proven allograft rejection will be adjudicated by a blinded adjudication committee per protocol.
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
2	UCLA Health - Westwood	Los Angeles	California	United States	90095-8344
3	UCSF - Infectious Disease Clinic	San Francisco	California	United States	94143-2202
4	Stanford University	Stanford	California	United States	94305
5	Yale University School of Medicine	New Haven	Connecticut	United States	06510-3206
6	Mayo Clinic Florida	Jacksonville	Florida	United States	32224-1865
7	University of Miami, Jackson Memorial Hospital	Miami	Florida	United States	33136-1101
8	Tampa General Medical Group	Tampa	Florida	United States	33606-2707
9	Piedmont Transplant Institute	Atlanta	Georgia	United States	30309
10	Emory University Hospital	Atlanta	Georgia	United States	30322
11	Northwestern University, Feinberg School of Medicine	Chicago	Illinois	United States	60611-2945
12	University of Kentucky Medical Center	Lexington	Kentucky	United States	40536
13	Tulane University Medical Center	New Orleans	Louisiana	United States	70112-2600
14	University Of Maryland Medical Center	Baltimore	Maryland	United States	21201-1009
15	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287-0020
16	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655-0002
17	Henry Ford Health System	Detroit	Michigan	United States	48202
18	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
19	Columbia University Medical Center	New York	New York	United States	10032-3720
20	Carolinas Medical Center	Charlotte	North Carolina	United States	28207-1248
21	University of Cincinnati	Cincinnati	Ohio	United States	45267-2827
22	University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania	United States	19104
23	Baylor All Saints Medical Center	Fort Worth	Texas	United States	76104-4110
24	Swedish Medical Center	Seattle	Washington	United States	98104
25	University of Washington Medical Center	Seattle	Washington	United States	98195-0001
26	University of Wisconsin	Madison	Wisconsin	United States	53792