Recombinant Human C1 Inhibitor for the Treatment of Early Antibody-Mediated Rejection in Renal Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Efficacy will be defined as renal allograft survival 6 months following treatment for AMR. Renal allograft loss will be defined as either (1) subject death, (2) return to dialysis for greater than 30 days, or (3) re-transplantation.
研究概览
简要总结
The purpose of this study will be to assess the safety, tolerability, and efficacy of rhC1INH in renal transplant recipients with biopsy-confirmed antibody-mediated rejection (AMR) within 30 days of renal transplantation. This study will combine the investigational drug rhC1INH with a standard regimen of plasmapheresis (PP) and intravenous immune globulin (IVIG) and compare this to PP and IVIG alone.
详细描述
This is an Investigator-initiated, prospective, open-label, randomized, adaptive design study to enroll 30 adult renal transplant recipients with biopsy-confirmed AMR within 30 days post transplantation. After informed consent is obtained and study eligibility is confirmed, subjects will be enrolled immediately after biopsy confirmation of AMR and positive donor specific antibody (DSA). Subjects will then be randomized into one of two treatment groups (SOC [control] or rhC1INH). An initial cohort of 8 subjects (3 SOC, 5 rhC1INH) will receive intensive safety monitoring of the coagulation system and for thromboembolic events.
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
- 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
- •Recipients of renal transplantation within 30 days prior to enrollment.
- •AMR documented by light microscopic changes and immunohistochemical C4d staining on renal biopsy within 30 days post-transplant.
- •Positive DSA as detected by magnetic microbeads using a Luminex® system.
- •Age ≥ 18 years.
- •Women of child-bearing potential (CBP) must have negative pregnancy test at screening.
- •Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study and for 3 months following discontinuation of assigned treatment.
- •Subjects must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.
排除标准
- •Recipients of multi-organ transplants.
- •Recipients with previous early AMR.
- •Recipients with a known hypersensitivity to C1INH, rabbit anti-thymocyte globulin, or any rabbit protein.
- •History of malignancy within 3 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
- •Subjects who are positive for hepatitis C, hepatitis B surface antigen, or HIV at the time of transplant.
- •Subjects who are actively taking an investigational drug.
- •Subjects with a history of a psychological illness or condition that could interfere with the subject's ability to understand the requirements of the study.
- •Female subjects who are pregnant or nursing.
- •Subjects with hemodynamic instability, as defined by a mean arterial pressure (MAP) <60 mmHg or >110 mmHg; or requirement of vasopressors to maintain a MAP of 60 mmHg; or requirement of IV vasodilators for hypertensive emergency; or acute pulmonary edema.
- •Subjects with known active infection at the time of enrollment.
- •Biopsy-confirmed concurrent cellular rejection requiring polyclonal antibody therapy (i.e., all Grades other than Banff 1a and 1b will be excluded).
研究组 & 干预措施
Standard of Care (PP + IVIG)
Plasmapheresis and IVIG 100mg/kg every other day x 5 treatments
干预措施: plasmapheresis and IVIG (Procedure)
PP + IVIG + rhC1INH
Plasmapheresis + 100mg/kg IVIG every other day x 5 treatments plus rhC1Inh 100u/kg IV daily x 7 consecutive days (once daily on PP days, twice daily on non-PP days).
干预措施: recombinant C1 inhibitor (Drug)
结局指标
主要结局
Efficacy will be defined as renal allograft survival 6 months following treatment for AMR. Renal allograft loss will be defined as either (1) subject death, (2) return to dialysis for greater than 30 days, or (3) re-transplantation.
时间窗: 6 month
次要结局
未报告次要终点