Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates

NCT ID: NCT06075745

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 416 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-05
• Study Completion Date: 2028-02-28

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Vaccine Arm

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

Group Type: EXPERIMENTAL

CMV-MVA Triplex

Intervention Type: 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

Placebo Arm

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

Group Type: PLACEBO_COMPARATOR

Placebo for CMV-MVA Triplex

Intervention Type: DRUG

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

Interventions

CMV-MVA Triplex

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

Intervention Type: DRUG

Placebo for CMV-MVA Triplex

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Subject must be able to understand and provide informed consent

2. 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)

3. Negative human immunodeficiency virus (HIV) testing and no clinical suspicion of HIV infection

4. Planned for a first living donor liver transplant or listed/anticipated to be listed for a first deceased donor liver transplant.

5. Anticipated to receive a liver transplant within 1-12 months

6. 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)

7. 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)

8. 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:

1. 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

2. For women of reproductive potential as defined previously, a negative serum or urine pregnancy test (performed within 72 hours)

Exclusion Criteria

1. Women who are breastfeeding or planning to breastfeed

2. Prior Cytomegalovirus (CMV) vaccination

3. Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes coronavirus disease (COVID) convalescent plasma)

4. Currently enrolled in another interventional study that, in the investigator's opinion, could affect the evaluation of safety and/or vaccine effect outcomes

5. Prior (ever) receipt of a stem cell transplant (Peripheral blood stem cell (PBSC), marrow, cord blood, etc.)

6. 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)

7. Transplant status 1A or in the opinion of the investigator is likely to receive a transplant within the next month

8. At the time of randomization, either listed for, or, in the opinion of the investigator, likely to receive any non-liver organ transplant

9. Receipt of a clinical vaccine < 14 days before or planned to receive a clinical vaccine <14 days after the study agent

10. Known allergy to any component of the study agent

11. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study

1. Anaphylaxis or other severe reaction (Grade 4) considered definitely or probably attributable to dose 1

2. Receipt of liver transplant prior to dose 2

3. The participant must not have any severe acute illness or other factor, that, in the opinion of the investigator, requires postponement of dose 2 because of safety concerns. The participant can be re-evaluated for eligibility throughout the window of eligibility for the dose 2, once the illness or other factor has improved or resolved

4. Receipt of a clinical vaccine < 14 days before or planned to receive a clinical vaccine <14 days after the study agent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ajit P Limaye, MD

Role: STUDY_CHAIR

University of California, San Francisco: Transplantation

Cindy Fisher, M.D.

Role: STUDY_CHAIR

University of Washington Medical Center: Transplantation

Locations

University of Alabama at Birmingham, School of Medicine

Birmingham, Alabama, United States

Site Status: WITHDRAWN

University of California, San Diego School of Medicine

La Jolla, California, United States

Site Status: RECRUITING

Stanford University

Redwood City, California, United States

Site Status: RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status: RECRUITING

University of Miami, Jackson Memorial Hospital

Miami, Florida, United States

Site Status: RECRUITING

Emory University Hospital

Atlanta, Georgia, United States

Site Status: RECRUITING

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, United States

Site Status: RECRUITING

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status: RECRUITING

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Mayo Clinic, Rochester - College of Medicine and Science

Rochester, Minnesota, United States

Site Status: RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status: RECRUITING

Duke University School of Medicine

Durham, North Carolina, United States

Site Status: RECRUITING

Oregon Health & Sciences University

Portland, Oregon, United States

Site Status: RECRUITING

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Vanderbilt University School of Medicine

Nashville, Tennessee, United States

Site Status: RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

University of Washington Medical Center: Transplantation

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Saima Aslam, MD

Role: primary

saslam@health.ucsd.edu

619-543-6146

Dora Yuk-Wai Ho, MD, PhD

Role: primary

jsbach@stanford.edu

650-736-2442

Monica Fung, MD, MPH

Role: primary

monica.fung@ucsf.edu

415-353-1275

Yoichiro Natori, MD, MPH

Role: primary

yxn138@med.miami.edu

Please email

Aneesh Mehta, MD

Role: primary

aneesh.mehta@emory.edu

Please email

Michael Angarone, DO

Role: primary

m-angarone@northwestern.edu

312-695-6601

Robin Avery, MD

Role: primary

ravery4@jhmi.edu

410-614-6702

Kevin Gregg, MD

Role: primary

kvngregg@med.umich.edu

734-232-1486

Raymund Razonable, MD

Role: primary

Razonable.Raymund@mayo.edu

507-255-7761

Sias Scherger, MD

Role: primary

sscherger@unmc.edu

402-559-8650

Matthew Kappus, MD

Role: primary

matthew.kappus@duke.edu

919-385-5487

Lynne Strasfeld, MD

Role: primary

strasfel@ohsu.edu

503-494-7735

Emily Blumberg, MD

Role: primary

eblumber@pennmedicine.upenn.edu

Please email

Fernanda Silveira, MD, MS

Role: primary

silvfd@upmc.edu

412-648-6512

Suzanne Sharpton, MD

Role: primary

suzanne.sharpton@vumc.org

Please email

Ricardo La Hoz, MD

Role: primary

ricardo.lahoz@utsouthwestern.edu

205-306-5037

Cindy P. Fisher, MD

Role: primary

celaine@uw.edu

206-598-9149

Related Links

http://www.ctotstudies.org

Clinical Trials in Organ Transplantation

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation

Other Identifiers

DAIT CTOT-44

Identifier Type: -

Identifier Source: org_study_id