Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates

NCT06075745 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT CTOT-44
• Study Type: interventional
• Target: 416
• Locations: 1 country
• Sites: 18

Brief Summary

This is a multi-center clinical trial in Cytomegalovirus (CMV) seronegative prospective liver transplant recipients to determine the efficacy of two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine pre-transplant. The primary objective is to assess the effect of pre-transplant (Tx) Triplex vaccination on duration of CMV antiviral therapy (AVT) within the first 100 days post-Tx in CMV seropositive donor (D+) and seronegative (R-) (D+R-) liver transplant recipients (LTxRs). A protocol-mandated preemptive therapy (PET) will be used for CMV disease prevention in D+R- LTxRs.

Conditions

Liver Transplant

Keywords

Cytomegalovirus; Vaccine; Orthotopic Liver Transplant

Outcome Measures

Primary Outcomes (6)

• Total days of Cytomegalovirus (CMV) active antiviral therapy (AVT) in CMV seropositive donor (D+) and seronegative (R-) and (D+R-) liver transplant recipients

  Within the first 100 days post-transplantation

• Percent of participants with solicited adverse reactions

  Consisting of local reactions including: injection site pain, swelling, erythema (redness); systemic reactions: fever, headache, muscle ache, fatigue)

  Within 7 days of each dose

• Percent of participants with pre-transplant treatment emergent serious adverse events (TESAE)

  Within 100 days after initial dose

• Percent of participants with pre-transplant treatment emergent serious adverse events (TESAE)

  Within 28 days after each dose

• Percent of participants with pre-transplant treatment emergent adverse events (TEAE)

  Grade \>=3 severity or increase of severity of baseline abnormality that results in grade \>= 3 severity

  Within 28 days after each dose

• Percent of participants with treatment emergent serious adverse events (TESAE)

  Grade \>= 4 severity

  Throughout the study

Secondary Outcomes (7)

• Percent of seropositive donor (D+) and seronegative (R-) liver transplant recipients (D+R- LTxRs) who develop Endpoint-Committee adjudicated Cytomegalovirus (CMV) disease

  By 6 months post-transplant (Tx)

• Percent of seropositive donor (D+) and seronegative (R-) liver transplant recipients (D+R- LTxRs) who develop investigator-reported Cytomegalovirus (CMV) disease

  By 6 months post-transplant (Tx)

• Time to onset of Endpoint-Committee adjudicated Cytomegalovirus (CMV) disease in seropositive donor (D+) and seronegative (R-) (D+R-) liver transplant recipients

  By 6 months post-transplant (Tx)

• Time to onset of Endpoint-Committee adjudicated Cytomegalovirus (CMV) in seropositive donor (D+) and seronegative (R-) (D+R-) liver transplant recipients

  By 6 months post-transplant (Tx)

• Time to onset of investigator-reported Cytomegalovirus (CMV) disease

  By 6 months post-transplant (Tx)

Study Arms (2)

Vaccine Arm

EXPERIMENTAL

Participants in this arm will receive two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine

Drug: CMV-MVA Triplex

Placebo Arm

PLACEBO COMPARATOR

Participants will receive two doses of matching placebo of the Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine

Drug: Placebo for CMV-MVA Triplex

Interventions

CMV-MVA Triplex DRUG

The dosage used will be 5.0 x 10\^8 pfu, administered under sterile conditions intramuscularly. The CMV-MVA Triplex vaccine lots range in titre from 5.0 to 9.0 x 10\^8 pfu/mL in a supplied volume of 1.0 mL

Vaccine Arm

Placebo for CMV-MVA Triplex DRUG

Arm 2 participants receive two doses of matching placebo CMV-MVA Triplex

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be able to understand and provide informed consent
• Negative for Cytomegalovirus (CMV) IgG antibody as assessed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory within 12 months of enrollment, and no history of prior positive CMV serology (IgG antibody)
• Negative human immunodeficiency virus (HIV) testing and no clinical suspicion of HIV infection
• Planned for a first living donor liver transplant or listed/anticipated to be listed for a first deceased donor liver transplant.
• Anticipated to receive a liver transplant within 1-12 months
• For individuals of reproductive potential, a negative serum or urine pregnancy test within 72 hours prior to enrollment. NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) \>=40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy)
• Participants who are able to impregnate or become pregnant (i.e., of reproductive potential) and are participating in sexual activity that could lead to pregnancy must agree to practice contraception/birth control (hormonal or barrier method) or agree to not participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for at least 1 month following the last vaccine/placebo dose. For acceptable contraception methods that are more than 80 percent effective, see Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol)
• The most recent platelet count is \>= 20,000 cells/mm\^3 within 3 months prior to enrollment and in the opinion of the investigator, has not decreased \< 20,000 cells/mm\^3 at time of study IP administration.
• Eligibility criteria required: Dose 2:
• Most recent platelet count \>= 20,000 cells/mm\^3 within 3 months prior to enrollment and in the opinion of the investigator, has not decreased \< 20,000 cells/mm\^3 since last result
• For women of reproductive potential as defined previously, a negative serum or urine pregnancy test (performed within 72 hours)

You may not qualify if:

• Women who are breastfeeding or planning to breastfeed
• Prior Cytomegalovirus (CMV) vaccination
• Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes coronavirus disease (COVID) convalescent plasma)
• Currently enrolled in another interventional study that, in the investigator's opinion, could affect the evaluation of safety and/or vaccine effect outcomes
• Prior (ever) receipt of a stem cell transplant (Peripheral blood stem cell (PBSC), marrow, cord blood, etc.)
• Receipt of immunosuppression:
• Within the last 3 months prior to randomization:
• Systemic Chemotherapy or immunotherapy for cancer in the last 3 months (localized therapy for hepatocellular carcinoma \[HCC\] such as chemoembolization, Y-90 are not considered "systemic chemotherapy" and are not excluded)
• Systemic immunosuppressive agents (e.g., cyclophosphamide, methotrexate, mycophenolate, azathioprine, calcineurin inhibitors, mTOR inhibitors, TNF-alpha inhibitors) and/or combination immunosuppressive drugs for any autoimmune or other conditions in the last 3 months except corticosteroids as below
• Within the last 28 days prior to randomization: averaged daily corticosteroid therapy dose ≥20 mg of prednisone equivalent
• Within the last 6 months prior to randomization: receipt of T- or Bcell depleting agents (e.g. ATG, Alemtuzumab, Rituximab)
• Transplant status 1A or in the opinion of the investigator is likely to receive a transplant within the next month
• At the time of randomization, either listed for, or, in the opinion of the investigator, likely to receive any non-liver organ transplant
• Receipt of a clinical vaccine \< 14 days before or planned to receive a clinical vaccine \<14 days after the study agent
• Known allergy to any component of the study agent

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (18)

University of Alabama at Birmingham, School of Medicine

Birmingham, Alabama, 35233, United States

WITHDRAWN

University of California, San Diego School of Medicine

La Jolla, California, 92093, United States

RECRUITING

Stanford University

Redwood City, California, 94063-3126, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143-0000, United States

RECRUITING

University of Miami, Jackson Memorial Hospital

Miami, Florida, 33136-1003, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322-0000, United States

RECRUITING

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611-0000, United States

RECRUITING

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205-0000, United States

RECRUITING

University of Michigan Medical Center

Ann Arbor, Michigan, 48109-1274, United States

RECRUITING

Mayo Clinic, Rochester - College of Medicine and Science

Rochester, Minnesota, 55905-0001, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7835, United States

RECRUITING

Duke University School of Medicine

Durham, North Carolina, 27710-1000, United States

RECRUITING

Oregon Health & Sciences University

Portland, Oregon, 97239-3098, United States

ACTIVE NOT RECRUITING

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104-5127, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213-0000, United States

RECRUITING

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232-0011, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-0000, United States

RECRUITING

University of Washington Medical Center: Transplantation

Seattle, Washington, 98195, United States

RECRUITING

Related Links

• Clinical Trials in Organ Transplantation
• National Institute of Allergy and Infectious Diseases
• Division of Allergy, Immunology, and Transplantation

Study Officials

• Ajit P Limaye, MD

  University of California, San Francisco: Transplantation

  STUDY CHAIR

• Cindy Fisher, M.D.

  University of Washington Medical Center: Transplantation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2023
• First Posted: October 10, 2023
• Study Start: March 5, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial
• Access Criteria: Open access

Locations

US (18)