Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates

Phase 2

Recruiting

• Conditions: Liver Transplant
• Interventions: Drug: CMV-MVA Triplex; Drug: Placebo for CMV-MVA Triplex

• Registration Number: NCT06075745
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2023-10-04
• Study First Submitted QC: 2023-10-04
• Study First Posted: 2023-10-10
• Study Start: 2024-03-05
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-27
• Primary Completion: 2027-06-30
• Study Completion: 2028-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 416

Inclusion Criteria

1. Subject must be able to understand and provide informed consent
2. Negative for antibody to Cytomegalovirus (CMV) as assessed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory within 6 months of enrollment, and no history of prior positive CMV serology (IgG antibody)
3. Negative screening test for human immunodeficiency virus (HIV) and no clinical suspicion of HIV infection
4. Listed for a first living or 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 within 3 months prior to enrollment by any laboratory with CLIA certification or equivalent of >= 20,000 cells/mm^3 prior to enrollment, and in the opinion of the investigator, has not decreased < 20,000 cells/mm^3 at time of IP administration.

Eligibility criteria required: Dose 2:

1. Most recent platelet count >= 20,000 cells/mm^3 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)

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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:

   1. 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)
   2. 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

7. Averaged daily corticosteroid therapy at a dose >=20 mg of prednisone equivalent in the last 28 days prior to randomization

8. Receipt of T- or B-cell depleting agents (e.g., ATG, Alemtuzumab, Rituximab) within the last 6-months prior to randomization

9. Transplant status 1A or in the opinion of the investigator is likely to receive a transplant within the next 2 months

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

11. Receipt of or planned administration of:

    1. Live, attenuated vaccine within 14 days of study agent
    2. Subunit or inactivated vaccine within 14 days of study agent

12. Known allergy to any component of the study agent

13. 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vaccine Arm	CMV-MVA Triplex	Participants in this arm will receive two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine
Placebo Arm	Placebo for CMV-MVA Triplex	Participants will receive two doses of matching placebo of the Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine

Primary Outcome Measures

Name	Time	Method
Percent of participants with pre-transplant treatment emergent adverse events (TEAE)	Within 28 days after each dose	Grade \>=3 severity or increase of severity of baseline abnormality that results in grade \>= 3 severity
Percent of participants with pre-transplant treatment emergent serious adverse events (TESAE)	Within 28 days after each dose
Percent of participants with treatment emergent serious adverse events (TESAE)	Throughout the study	Grade \>= 4 severity
Percent of participants with solicited adverse reactions	Within 7 days of each dose	Consisting of local reactions including: injection site pain, swelling, erythema (redness); systemic reactions: fever, headache, muscle ache, fatigue)
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

Secondary Outcome Measures

Name	Time	Method
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) 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)
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)
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 Endpoint committee adjudicated CMV disease	Within first 100 days post-transplant (Tx)
Percent of seropositive donor (D+) and seronegative (R-) liver transplant recipients (D+R- LTxRs) who develop CMV DNAemia >= 1000 IU/mL	Within first 100 days post-transplant (Tx)

Trial Locations

Locations (18)

University of Alabama at Birmingham, School of Medicine; 🇺🇸 Birmingham, Alabama, United States

University of California, San Diego School of Medicine; 🇺🇸 La Jolla, California, United States

Stanford University; 🇺🇸 Redwood City, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

University of Miami, Jackson Memorial Hospital; 🇺🇸 Miami, Florida, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

Northwestern University, Feinberg School of Medicine; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States

University of Michigan Medical Center; 🇺🇸 Ann Arbor, Michigan, United States

Mayo Clinic, Rochester - College of Medicine and Science; 🇺🇸 Rochester, Minnesota, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Duke University School of Medicine; 🇺🇸 Durham, North Carolina, United States

Oregon Health & Sciences University; 🇺🇸 Portland, Oregon, United States

University of Pennsylvania School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Vanderbilt University School of Medicine; 🇺🇸 Nashville, Tennessee, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

University of Washington Medical Center: Transplantation; 🇺🇸 Seattle, Washington, United States