NCT02547220终止3 期
A Randomized Double-blind Placebo-controlled Study to Evaluate the Efficacy and Safety of Cinryze® (C1 Esterase Inhibitor [Human]) for the Treatment of Acute Antibody-mediated Rejection in Kidney Transplant Patients
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Shire
- 入组人数
- 39
- 试验地点
- 47
- 主要终点
- Percentage of Participants With New or Worsening Transplant Glomerulopathy (TG) at Month 6 Post-Treatment
研究概览
简要总结
The main purpose of the study is to evaluate the efficacy of CINRYZE administered with plasmapheresis, plasma exchange, or immune adsorption treatments and sucrose-free immunoglobulin (IVIg) for the treatment of acute antibody-mediated rejection (AMR) of renal allograft in kidney transplant recipients as measured by the proportion of participants with new or worsening transplant glomerulopathy (TG) at 6 months after treatment initiation.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be greater than or equal to (>=) 18 and less than or equal to (<=) 70 years of age.
- •Weigh >= 45 kg with a body mass index (BMI) less than (<) 35 kilogram (kg)/meter (m)^2 at screening.
- •Have human leukocyte antigen (HLA) donor-specific antibody (DSA) identified at the time of diagnosis of AMR. If it is anticipated that the local DSA results will not be available within the screening period, previously obtained local DSA results can be used to assess eligibility, if obtained after kidney transplant and within 30 days prior to the qualifying AMR episode. In any instance, a local DSA test should still be performed at the time of AMR diagnosis.
- •Have a first qualifying episode of AMR in the participant's current renal allograft between 72 hours (h) and 12 months after transplant defined by a renal allograft biopsy demonstrating neutrophil and/or monocyte infiltration in the peritubular capillaries (PTC) and/or glomeruli with or without evidence of 4th complement protein degradation product (C4d) deposition by immunohistopathology according to 2013 Banff criteria.
- •Have achieved adequate renal function defined as: Pre-AMR baseline estimated glomerular filtration rate calculated by the Modification of Diet in Renal Disease (eGFRMDRD) >=20 millilitre (mL)/minute (min) /1.73m^2 for a qualifying AMR episode occurring <=21 days after transplant or pre-AMR baseline eGFRMDRD >=30 mL/min/1.7m^2 for a qualifying AMR episode occurring greater than (>) 21 days after transplant. The pre-AMR baseline is the highest eGFRMDRD value obtained following the kidney transplant and within 30 days prior to the qualifying AMR episode. If more than 1 eGFRMDRD value is available, a mean of the 2 highest values (at least 1 day apart and both prior to the AMR episode) will be used as the pre-AMR baseline value. If no eGFRMDRD was obtained within 30 days prior to biopsy, it can be evaluated within a 60 day period.
- •Receive first dose of investigational product after 7 days after the kidney transplant procedure and within 7 days after the qualifying renal allograft biopsy procedure that was positive for AMR.
- •Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
- •If female and of child-bearing potential, must have a negative urine pregnancy test confirmed by a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at the Screening Visit and must have a negative urine pregnancy test at the Day 1 visit.
- •Agree to comply with any applicable contraceptive requirements of the protocol.
排除标准
- •Have received pediatric en bloc kidney transplant.
- •Have primary Focal Segmental Glomerulosclerosis, rapidly progressive glomerulonephritis, membrano-proliferative glomerulonephritis type 1 (including C3 glomerulopathy), "dense deposit disease", or thrombotic microangiopathy as the cause of native kidney failure.
- •Have prior or concurrent non-renal solid organ transplant or hematopoietic stem cell transplant (HSCT) or have more than 2 completed kidney transplant procedures (note: 1 double kidney transplant procedure is considered to be 1 procedure).
- •Have a known neoplastic lesion in the transplanted allograft
- •Have, any ongoing infection that causes hemodynamic compromise or as determined by the investigator, any surgical or medical condition that could interfere with the administration of investigational product, interpretation of study results, or could compromise participant safety, including (as determined by the transplanting surgeon and documented in the operative report) any major technical complications of the renal artery, renal vein, or ureteral anastomosis
- •Have ongoing treatment for hepatitis C virus (HCV) infection.
- •Have had a recent myocardial infarction (MI) within the past 6 months and/or at the time of screening are treated with anticoagulants and/or antiplatelet agents (excluding aspirin) for a previous myocardial infarction.
- •Have a history of: abnormal bleeding, clotting events or disorders (excluding a history of clotted hemodialysis access or superficial thrombophlebitis in the absence of medically confirmed coagulopathy), any coagulopathy (documented or clinically suspected) For example, participants should be excluded if they have a history of renal allograft arterial or venous thrombosis, deep vein thrombosis, pulmonary embolism, ischemic cerebrovascular accident (stroke) or transient ischemic attack (TIA), any large vessel thrombosis.
- •Have a history of allergic reaction to CINRYZE or other blood products.
- •Have had any change in androgen therapy (example, danazol, oxandrolone, stanozolol, testosterone), tranexamic acid, epsilon-aminocaproic acid, or other fibrinolytics within 3 months before the first dose of investigational product.
- •Have participated in the active dosing phase of any other investigational drug study within 30 days prior to dosing with investigational product.
- •Have any of the following local laboratory values reported prior to dosing with investigational product: Within 24 h prior to participant dosing, white blood cell (WBC) count <0.5×109/litre (L) or >20×109/L (the value of >20×109/L should be excluded if obtained during steroid treatment), Within 24 h prior to participant dosing platelet count <25×109/L or >600×109/L
- •Be pregnant or breastfeeding.
- •Have received any of the following agents within 1 month prior to the first dose of investigational product: Sucrose-containing intravenous immunoglobulin (IVIg), Any C1 inhibitor (C1 INH) (plasma-derived [example, CINRYZE®, Berinert®, Cetor®] or recombinant [example, Rhucin®]), Eculizumab (Soliris®), Ecallantide (Kalbitor®).
研究组 & 干预措施
Cinryze®
Experimental
Participants will receive 5000 Units of CINRYZE (50 millilitre [mL] of CINRYZE/ 50 mL of normal saline) on Day 1 and 2500 Units of CINRYZE (25 mL of CINRYZE/ 75 mL of normal saline) on Day 3, 5, 7, 9, 11, and 13 respectively.
干预措施: Cinryze® (Biological)
Placebo
Placebo Comparator
Participants will receive 7 doses of matched placebo over 13 days of treatment.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With New or Worsening Transplant Glomerulopathy (TG) at Month 6 Post-Treatment
时间窗: Month 6
New or worsening TG at month 6 by the standard score was defined as an increase in one or more between qualifying biopsy and 6-month biopsy. New or worsening TG was measured by Banff 2013 criteria (standard score) using allograft glomerulopathy (Cg0-Cg3): Cg0- No GBM double contours by light microscopy (LM) or electron microscopy (EM); Cg1- no GBM double contours by LM but GBM double contours in at least 3 glomerular capillaries by EM; Cg2- Double contours affecting 26 to 50% of peripheral capillary loops in the most affected of nonsclerotic glomeruli; Cg3- Double contours affecting more than 50% of peripheral capillary loops in the most affected of nonsclerotic glomeruli with a score range of 0 (no allograft glomerulopathy) and 3 (severe glomerulopathy). Percentage of participants with new or worsening TG at Month 6 post-treatment was reported.
次要结局
- Number of Participants With All-Cause Graft Failure at Month 48(Month 48)
- Time to All-Cause Graft Failure up to Month 48(Up to Month 48)
- Time to Graft Failure Due to Antibody-Mediated Rejection (AMR) Episodes up to Month 48(Up to Month 48)
- Number of Participants With Resolution of the Qualifying Antibody-Mediated Rejection (AMR) Episodes at Month 48(Month 48)
- Time to Resolution of Qualifying Antibody-Mediated Rejection (AMR) Episodes up to Month 48(Up to Month 48)
- Change From Baseline in Renal Function up to Month 48(Baseline, up to Month 48)
- Change From Baseline With Pre-Antibody-Mediated Rejection (AMR) in Renal Function up to Month 48(Pre-AMR Baseline, up to Month 48)
- Change From Pre-Antibody-Mediated Rejection (AMR) Baseline in Histopathology Per Banff Criteria at Month 6(Pre-AMR Baseline, Month 6)
- Number of Participants With Proteinuria Levels at Month 48(Month 48)
- Number of Participants Who Were Alive at Month 36(Month 36)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From start of study drug administration up to study termination (Month 36))
- Number of Participants With All-Cause Graft Failure at Month 6(Month 6)
- Number of Participants With Graft Failure Due to Antibody-Mediated Rejection (AMR) Episodes at Month 48(Month 48)
- Time to All-Cause Mortality up to Month 48(Up to Month 48)
研究者
研究点 (47)
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