A 12-Month, Open-Label Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Siplizumab as Induction Therapy in Patients With Autoimmune Liver Diseases Undergoing Liver Transplantation (SET-SAIL)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Serious infection in the first month post-transplant,
研究概览
简要总结
There is a significant unmet need for safe and effective therapeutic approaches to prevent immune-mediated graft injury and its complications in liver transplant (LT) recipients with autoimmune liver disease (AILD) including autoimmune hepatitis and primary sclerosing cholangitis. Siplizumab is an anti-cluster of differentiation 2 (CD2) monoclonal antibody that has demonstrated a favorable safety profile of siplizumab in over 779 human subjects and has been shown to target memory T cells-a key driver in the immune processes surrounding rejection and autoimmunity post LT in AILD. The purpose of this pilot, open-label phase 1 study is to determine the safety of siplizumab for induction in patients with AILD undergoing LT.
Up to eight (8) subjects will receive siplizumab 0.6 mg/kg/dose on the day of transplant (Day 0) and Day 4 post-transplant, for a total of two doses.
All subjects will be followed in the study for 12 months post-LT.
详细描述
The purpose of this study is to evaluate the safety of siplizumab when used as induction immunosuppression in patients with primary sclerosing cholangitis (PSC) or autoimmune hepatitis (AIH) undergoing liver transplantation. Induction immunosuppression drugs are very potent anti-rejection drugs that are given immediately after transplantation to prevent rejection. Siplizumab is investigational, meaning it has not yet been approved for market use for this disease condition by the United States Food and Drug Administration (FDA).
Adult patients (18 years of age and older) listed for LT with the specific AILD diagnoses of PSC or AIH
All subjects will receive 0.6 mg/kg/dose intravenously on the day of transplant (Day 0) intraoperatively and on post-transplant Day 4.
Participation in this study will last approximately 15 months (~ 3 months on the LT waitlist, up to 12 months participation post-LT)
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide informed consent
- •Age ≥ 18 years old
- •Clinical diagnosis of AIH and/or PSC
- •Listed for liver transplantation
- •Epstein-Barr virus (EBV) seropositive within 12 months of screening
排除标准
- •Presence or history of significant liver disease other than AIH or PSC, including viral hepatitis, alcohol-related liver disease and biopsy-proven non-alcoholic steatohepatitis
- •Prior transplant
- •Listed for multiorgan transplant
- •Acute liver failure
- •Known malignancy, including cholangiocarcinoma and hepatocellular carcinoma
- •Other investigational products in the last 30 days or 5 half lives
- •Pregnant/lactating or unwilling to use contraception
- •Leukopenia (WBC less than 2,000/mm3
- •Absolute lymphocyte count < 200/mm3
- •Sero-positive for HIV-1
- •Hepatitis C Virus (HCV) antibody or RNA positive (within 6 months of screening)
- •HBsAg, hepatitis B virus (HBV) DNA or HBcAb positive (within 6 months of screening)
- •Alcohol use exceeding 30g/day for men or 20g/day for women, and/or known phosphatidylethanol (PETH) level >80 in the 3 months prior to LT
- •Untreated latent TB infection as detected by QuantiFERON Gold Plus Interferon Gamma Release Assay (IGRA) (or current standard interferon gamma release assay for TB)
- •Receipt of any live-attenuated vaccine within 2 months of transplant.
- •ADDITIONAL exclusion criteria to be reviewed at the time of transplant
- •Renal failure with dialysis or with estimated glomerular filtration rate (eGFR) < 30 at the time of LT
- •Model for end-stage liver disease (MELD)-Na score >30
- •Donor features of Donation after Cardiac Death (DCD), HCV Ab or nucleic acid testing (NAT+), HBcAb or HBsAg+, or blood types A, B, and O incompatible organ
研究组 & 干预措施
Open Label
subjects will receive 0.6 mg/kg/dose intravenously on the day of transplant (Day 0) intraoperatively and on post-transplant Day 4.
干预措施: Siplizumab (Drug)
结局指标
主要结局
Serious infection in the first month post-transplant,
时间窗: 1 Month post-transplant
viral, bacterial or fungal infection that leads to readmission, prolonged hospitalization, reoperation, intensive care unit admission, graft loss or death.
次要结局
- Incidence of immune-mediated liver injury(12 month Post-transplant)
- Incidence of graft loss or death(12 month Post-transplant)
- Incidence of BPAR(12 month Post-transplant)
- Incidence of treated BPAR(12 month Post-transplant)
- Incidence of refractory BPAR(12 month Post-transplant)
- Incidence of development of donor specific antibodies (DSA)(12 month Post-transplant)
- Incidence of recurrent AILD(12 month Post-transplant)
研究者
Elizabeth C. Verna
Frank Cardile Associate Professor of Medicine
Columbia University