Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates

Liver Transplant Clinical Trial

— COLT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06075745
• Other study ID #: DAIT CTOT-44
• Status: Recruiting
• Phase: Phase 2
• Start date: March 5, 2024
• Est. completion date: February 28, 2028

Study information

• Verified date: April 2024
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 416
• Est. completion date: February 28, 2028
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

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

Related Conditions & MeSH terms

• Cytomegalovirus Infections
• Liver Transplant

Intervention

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

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham, School of Medicine	Birmingham	Alabama
United States	Northwestern University, Feinberg School of Medicine	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University School of Medicine	Durham	North Carolina
United States	University of California, San Diego School of Medicine	La Jolla	California
United States	University of Miami, Jackson Memorial Hospital	Miami	Florida
United States	Vanderbilt University School of Medicine	Nashville	Tennessee
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Sciences University	Portland	Oregon
United States	Stanford University	Redwood City	California
United States	Mayo Clinic, Rochester - College of Medicine and Science	Rochester	Minnesota
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington Medical Center: Transplantation	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Percent of participants with pre-transplant treatment emergent serious adverse events (TESAE)		Within 100 days after initial dose
Primary	Percent of participants with pre-transplant treatment emergent serious adverse events (TESAE)		Within 28 days after each dose
Primary	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
Primary	Percent of participants with treatment emergent serious adverse events (TESAE)	Grade >= 4 severity	Throughout the study
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Time to onset of investigator-reported Cytomegalovirus (CMV) disease		By 6 months post-transplant (Tx)
Secondary	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)
Secondary	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)

External Links

•   Clinical Trials in Organ Transplantation