Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates (COLT)

July 22, 2026 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates (CTOT-44)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
416

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Withdrawn
        • University of Alabama at Birmingham, School of Medicine
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • University of California, San Diego School of Medicine
        • Contact:
      • Redwood City, California, United States, 94063-3126
        • Recruiting
        • Stanford University
        • Contact:
      • San Francisco, California, United States, 94143-0000
        • Recruiting
        • University of California, San Francisco
        • Contact:
    • Florida
      • Miami, Florida, United States, 33136-1003
        • Recruiting
        • University of Miami, Jackson Memorial Hospital
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322-0000
        • Recruiting
        • Emory University Hospital
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611-0000
        • Recruiting
        • Northwestern University, Feinberg School of Medicine
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21205-0000
        • Recruiting
        • Johns Hopkins University School of Medicine
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-1274
        • Recruiting
        • University of Michigan Medical Center
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905-0001
        • Recruiting
        • Mayo Clinic, Rochester - College of Medicine and Science
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7835
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710-1000
        • Recruiting
        • Duke University School of Medicine
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Recruiting
        • Oregon Health & Sciences University
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-5127
      • Pittsburgh, Pennsylvania, United States, 15213-0000
        • Recruiting
        • University of Pittsburgh Medical Center
        • Contact:
          • Fernanda Silveira, MD, MS
          • Phone Number: 412-648-6512
          • Email: silvfd@upmc.edu
    • Tennessee
      • Nashville, Tennessee, United States, 37232-0011
        • Recruiting
        • Vanderbilt University School of Medicine
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390-0000
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington Medical Center: Transplantation
        • Contact:
          • Cindy P. Fisher, MD
          • Phone Number: 206-598-9149
          • Email: celaine@uw.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Exclusion criteria required: Dose 2:

  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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Vaccine Arm
Participants in this arm will receive two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine
Drug: 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
Placebo Comparator: Placebo Arm
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
Arm 2 participants receive two doses of matching placebo CMV-MVA Triplex

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent of participants with solicited adverse reactions
Time Frame: Within 7 days of each dose
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)
Time Frame: Within 100 days after initial dose
Within 100 days after initial dose
Percent of participants with pre-transplant treatment emergent serious adverse events (TESAE)
Time Frame: Within 28 days after each dose
Within 28 days after each dose
Percent of participants with pre-transplant treatment emergent adverse events (TEAE)
Time Frame: Within 28 days after each dose
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)
Time Frame: Throughout the study
Grade >= 4 severity
Throughout the study
Total days of Cytomegalovirus (CMV) active antiviral therapy (AVT) in CMV seropositive donor (D+) and seronegative (R-) and (D+R-) liver transplant recipients
Time Frame: Within the first 100 days post-transplantation
Within the first 100 days post-transplantation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Time to onset of investigator-reported Cytomegalovirus (CMV) disease
Time Frame: By 6 months post-transplant (Tx)
By 6 months post-transplant (Tx)
Percent of seropositive donor (D+) and seronegative (R-) liver transplant recipients (D+R- LTxRs) who develop Endpoint-Committee adjudicated Cytomegalovirus (CMV) disease
Time Frame: By 6 months post-transplant (Tx)
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
Time Frame: By 6 months post-transplant (Tx)
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
Time Frame: By 6 months post-transplant (Tx)
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
Time Frame: By 6 months post-transplant (Tx)
By 6 months post-transplant (Tx)
Percent of seropositive donor (D+) and seronegative (R-) liver transplant recipients (D+R- LTxRs) who develop CMV DNAemia >= 1000 IU/mL
Time Frame: Within first 100 days post-transplant (Tx)
Within first 100 days post-transplant (Tx)
Percent of seropositive donor (D+) and seronegative (R-) liver transplant recipients (D+R- LTxRs) who develop Endpoint committee adjudicated CMV disease
Time Frame: Within first 100 days post-transplant (Tx)
Within first 100 days post-transplant (Tx)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Cindy Fisher, M.D., University of Washington Medical Center: Transplantation
  • Study Chair: Ajit P Limaye, MD, University of California, San Francisco: Transplantation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 5, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 4, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 10, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DAIT CTOT-44

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

IPD Sharing Time Frame

On average, within 24 months after database lock for the trial

IPD Sharing Access Criteria

Open access

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings