Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation: A Randomized, Open-Label, Pilot Intervention Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Baseline eGFR (Estimated Glomerular Filtration Rate)
研究概览
简要总结
This study is designed to assess the effectiveness of eculizumab in recipients of kidney transplantation with donor-specific antibodies (DSA) and worsening kidney function and to assess if eculizumab improves endothelial cell injury in the kidney.
The investigators hypothesize that complement inhibition with eculizumab will reduce allograft injury, resulting from less complement-mediated injury of endothelial cells and less endothelial cell activation.
详细描述
This study will address the clinical challenge that currently exists in the management of kidney transplant recipients who have developed de novo DSA, have deteriorating graft function, yet have no established treatment alternative.
This is a randomized, open-label, pilot intervention trial. Post transplant patients with deteriorating renal function (defined as 20% reduction in GFR) will be screened for the development of DSA and biopsied for the presence of C4d deposition. All patients with DSA and those meeting inclusion/exclusion criteria will undergo protocol renal biopsy and will be assessed for C4d deposition. Participants will be randomized to treatment with eculizumab plus standard of care (SOC) or SOC only. Randomization will be stratified by C4d status (C4d+/C4d-) with 10 subjects (7 eculizumab, 3 SOC only) in each stratum.
Eculizumab is an antibody that has been developed to inhibit the complement protein C5. Eculizumab will be delivered via IV according to the following schedule:
- Eculizumab Induction 600mg IV every 7 days for 4 doses
- Eculizumab 900mg IV 7 days later
- Eculizumab Maintenance 900mg IV every 14 days for total of 26 weeks
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Kidney transplant recipients greater than 6 months from the date of transplant
- •Must be on standard immunosuppression: tacrolimus, mycophenolate mofetil, prednisone and have stable tacrolimus trough levels over past 3 months
- •Deteriorating renal function, as defined by 20% reduction in GFR (MDRD calculation)
- •Presence of DSA, as defined as MFI > 1100
- •Renal biopsy demonstrating no diffuse, irreversible end-stage organ injury (i.e. stage IV Fibrosis)
- •Renal biopsy demonstrating C4d deposition (stratum 1) or no C4d deposition (stratum 2)
排除标准
- •History of CMV, BK, HSV or other viral infections
- •History of chronic, recurrent bacterial infections
- •Evidence of tubulitis on renal biopsy or other morphological features of acute cellular rejection or acute humoral rejection
- •Renal biopsy demonstrating diffuse, irreversible end-stage organ injury
- •Absolute GFR < 25 (MDRD calculation)
- •Inability to provide informed consent
- •History of poor vascular access
- •Refusal to use double barrier contraception during study participation
- •Patients actively enrolled in other clinical trials
研究组 & 干预措施
Eculizumab
eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF [mycophenolate mofetil
], prednisone)
干预措施: eculizumab (Drug)
结局指标
主要结局
Baseline eGFR (Estimated Glomerular Filtration Rate)
时间窗: Baseline
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6
时间窗: Months 2,3,4,5,6
Primary statistical analysis of change from baseline was conducted with mixed effects modeling providing calculated estimates.
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR)
时间窗: 6 months
These data were calculated by mean 6-month eGFR minus baseline mean eGFR divided by baseline eGFR. Presented below are the between groups results. These results were derived from the results in the outcome "Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6".
次要结局
未报告次要终点
研究者
Sanjay Kulkarni
Associate Professor
Yale University