Early Signals of the Transition From Immune Quiescence to Activation in the Liver Allograft Microenvironment and in the Circulation (RTB-018)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 12
- 主要终点
- Achieving successful 50 percent Immunosuppression (IS) reduction
研究概览
简要总结
This is a prospective multi-center, longitudinal study to determine efficacy of 50 percent Immunosuppression (IS) reduction. One hundred fully eligible participants will reduce IS by 50 percent in two steps. Liver tests will be checked every 0.5 months through month 4, once a month through month 12, and every other month through month 18. Liver transplant (LTx) center visits will take place at screening, months 6, 12 and 18 after initiating IS dose reduction. A protocol driven liver biopsy to adjudicate the endpoint will be performed at 18 months. The duration of the study from time of starting IS dose reduction to the primary endpoint assessment is 18 months.
The primary objective is to assess the efficacy of 50 percent IS dose reduction in children with Liver transplants (LTxs)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 13 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant and parent or guardian must be able to understand and provide informed assent and consent, respectively
- •Recipient of a living or deceased donor Liver transplant (LTx) at <7 years of age
- •> 3 years but <7 years after LTx at the time of study enrollment
- •Stable liver tests defined as baseline serum alanine aminotransferase (ALT) level < 30 IU/l and gamma-glutamyl transferase (GGT) level < 50 IU/l (based on the average of the 3 most recent values prior to screening; all must be within 1 year of screening; 2 must be within 6 months of screening)
- •No Acute rejection (AR) or chronic rejection within 12 months of enrollment
- •Tacrolimus monotherapy for > 6 months with baseline 12-hour trough levels <8 ng/mL (based on the average of 3 values prior to screening; all must be within 1 year of screening; 2 must be within 6 months of screening)
- •Participants of childbearing potential must have a negative pregnancy test upon study entry
排除标准
- •Liver transplant (LTx) for autoimmune disease, including autoimmune hepatitis or primary sclerosing cholangitis
- •LTx for hepatitis B or hepatitis C
- •Recipient of any other organ transplant or liver re-transplant, except for patients who have a repeat LTx within 30 days of first LTx who are eligible for enrollment
- •>=50 percent dose increase in tacrolimus within 12 months of enrollment
- •Discontinued a second Immunosuppression (IS) agent within 12 months of enrollment
- •Systemic illness requiring chronic or recurrent use of IS for which there is a risk of reactivation if tacrolimus is reduced
- •Use of medication to treat systemic conditions which in the judgement of the investigator could influence results of the study
- •Active or chronic infection requiring treatment
- •Inability or unwillingness to comply with the study protocol
- •Use of investigational drug within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of enrollment
- •Has any condition that, in the opinion of the investigator, will interfere with safe participation in the trial
研究组 & 干预措施
IS dose reduction
Eligible participants will reduce immunosuppression (IS) by 50 percent in two steps. For subjects taking tacrolimus once daily:
- reduce dose to 75 percent of initial dose for 6 weeks
- reduce dose to 50 percent of initial dose
For subjects taking tacrolimus twice daily:
- reduce evening such that the total daily dose is 75 percent of the initial dose for 6 weeks
- stop evening dose
For participants taking different doses of tacrolimus in the morning and evening, the clinical site will confer will the protocol chair and PI to determine the schedule for IS reduction
干预措施: Immunosuppression Reduction (Drug)
结局指标
主要结局
Achieving successful 50 percent Immunosuppression (IS) reduction
时间窗: At 18 months
Defined as meeting both biochemical and histological criteria of stability
次要结局
- Clinical severity of Acute rejection (AR) episodes(At 18 months)
- Histological severity of Acute rejection (AR) episodes(At 18 months)
- The proportion of participants who experience Acute rejection (AR)(At 18 months)
- Achieving clinically successful 50 percent Immunosuppression (IS) reduction(At 18 months)
- Proportion of Acute Rejection (AR) Episodes Within Each Banff Severity Category(At 18 months)