Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant Candidates (CTOT-44)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 416
- 试验地点
- 37
- 主要终点
- Percent of participants with pre-transplant treatment emergent adverse events (TEAE)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
- •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:
- •Anaphylaxis or other severe reaction (Grade 4) considered definitely or probably attributable to dose 1
- •Receipt of liver transplant prior to dose 2
- •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
- •Receipt of a clinical vaccine < 14 days before or planned to receive a clinical vaccine <14 days after the study agent
研究组 & 干预措施
Vaccine Arm
Participants in this arm will receive two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine
干预措施: CMV-MVA Triplex (Drug)
Placebo Arm
Participants will receive two doses of matching placebo of the Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine
干预措施: Placebo for CMV-MVA Triplex (Drug)
结局指标
主要结局
Percent of participants with pre-transplant treatment emergent adverse events (TEAE)
时间窗: 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 solicited adverse reactions
时间窗: Within 7 days of each dose
Consisting of local reactions including: injection site pain, swelling, erythema (redness); systemic reactions: fever, headache, muscle ache, fatigue)
Percent of participants with pre-transplant treatment emergent serious adverse events (TESAE)
时间窗: Within 28 days after each dose
Percent of participants with treatment emergent serious adverse events (TESAE)
时间窗: Throughout the study
Grade \>= 4 severity
Total days of Cytomegalovirus (CMV) active antiviral therapy (AVT) in CMV seropositive donor (D+) and seronegative (R-) and (D+R-) liver transplant recipients
时间窗: Within the first 100 days post-transplantation
Percent of participants with pre-transplant treatment emergent serious adverse events (TESAE)
时间窗: Within 100 days after initial dose
次要结局
- 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))