A Randomized Double-Blind Placebo-Controlled Pilot Study to Evaluate the Safety and Effect of CINRYZE® (C1 Esterase Inhibitor [Human]) for the Treatment of Acute Antibody-Mediated Rejection in Recipients of Donor-Sensitized Kidney Transplants
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 18
- 试验地点
- 5
- 主要终点
- Change From Baseline in Histopathology Endpoints
研究概览
简要总结
The purpose of this research study is to evaluate the safety, effect, and pharmacology of C1 Esterase Inhibitor (human) in kidney transplant patients with acute Antibody-Mediated Rejection (AMR).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •≥18 years of age.
- •Weigh ≥50 kg.
- •Donor specific antibody identified.
排除标准
- •Any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
- •History of allergic reaction to C1 Esterase Inhibitor or other blood products.
- •Participation in the active dosing phase of any other investigational drug study within 30 days prior to dosing with study drug.
- •Pregnancy or lactation.
- •Receipt of any experimental agents for AMR within 1 month prior to the first dose of study drug.
- •Any infection that causes hemodynamic compromise.
- •History of bleeding or clotting abnormality.
结局指标
主要结局
Change From Baseline in Histopathology Endpoints
时间窗: Within 72 hours prior to first dose of study drug, Day 20
The protocol-specified Day 20 (post-treatment) biopsy was compared to the qualifying biopsy to assess changes in histopathology for light and immunofluorescence microscopy. The Central Pathologist provided the following categorical information from the qualifying biopsy in an AMR Scorecard: C4d Score (0-100), Margination Score (0-100) Glomerulitis Score (0-100), Vasculitis Score (0-100), Glomerulosclerosis Score (0-100), Chronic Glomerulopathy Score (0-100), Interstitial Fibrosis Score (0-100), and the Chronic Vasculitis Score (0-100), with 0 being absence of abnormal histopathology. The "qualifying" renal allograft biopsy was performed as standard of care (SOC) within 12 months after transplant and prior to screening for this study. The first dose of study drug (Day 1) was administered within 72 hours after qualifying biopsy. A negative change from baseline indicates that histopathology has improved. Endpoint includes subjects with both Qualifying and Day 20 Biopsies.
次要结局
- Number of Participants Who Required Salvage Splenectomy(From Day 1 to Day 90)
- Number of Participants With Resolution of The Qualifying Episode of Antibody-Mediated Rejection (AMR)(90 days after start of treatment)
- Change From Baseline in Serum Creatinine(From Day 1 to Days 20 and 90)
- Change From Baseline in Creatinine Clearance(From Day 1 to Days 20 and 90)
- Number of Plasmapheresis Sessions(From Day 1 through Days 20 and 90)
- Number of Participants With Allograft Failure(From the day of enrollment to Day 90)
- Serum Concentrations of C1 Inhibitor (C1 INH) Antigen(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)
- Number of Deaths(From Day 1 to Day 90)
- Serum Concentrations of C1 INH Functional Activity(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)
- Area Under The Concentration-Time Curve (AUC) of C1 INH Antigen(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)
- Time to Maximum Plasma Concentration (Tmax) of C1 INH(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)
- Area Under The Concentration-Time Curve (AUC) of C1 INH Functional Activity(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)