A Phase 2 Multicenter, Randomized, Open Label, Parallel Assignment, Pilot Study to Assess the Efficacy and Safety of Reparixin Following Islet Transplantation in Patients With Type 1 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- The Percentage of Insulin-independent Patients Following Single Infusion Islet Cell Transplantation at Day 75 +/- 5
研究概览
简要总结
Inhibition of CXCL8 activity might represent a relevant therapeutic target to prevent injury occurring after pancreatic islet transplantation. Reparixin is a novel and specific inhibitor of CXCL8. This study is designed to explore the efficacy of reparixin in preventing graft dysfunction after islet transplantation in type 1 diabetes patients (T1D).
详细描述
Pancreatic islet transplantation has become a feasible option in the treatment of T1D which offers advantages over whole pancreas transplantation. However to date insulin independence can be obtained in most cases only after the patient has received repeated infusions from several donors. A non-specific immune response, mediated predominantly by innate inflammatory processes, coupled with specific cellular immune responses, possibly promoted by early inflammation, play a major role in the loss of transplanted islets from the liver. PMNs have been found to be the predominant cell types infiltrating in vitro the islets. In this regard, CXCL8 has been shown to be expressed by human islets and could play a crucial role in triggering the inflammatory reaction. Thus, CXCL8 might represent a relevant therapeutic target to prevent early graft failure. The efficacy of reparixin in improving graft outcome in mice models of intrahepatic islet transplantation, as well as the safety shown in human phase 1 and 2 studies, provide a rationale for a clinical study aimed at evaluating the effect of reparixin in preventing graft dysfunction after islet transplantation in T1D patients.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Reparixin
Reparixin + Immunosuppression
Reparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.
Reparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.
For immunosoppression regimen see the other arm description.
干预措施: Reparixin (Drug)
结局指标
主要结局
The Percentage of Insulin-independent Patients Following Single Infusion Islet Cell Transplantation at Day 75 +/- 5
时间窗: day 75 +/- 5 post-transplant
Insulin-independence was defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycemic control, as defined by: * HbA1c level of less than 7%; * glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than 3 times a week (based on measuring capillary glucose level a minimum of 7 times in a 7-day period); * glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than 4 times a week (based on measuring capillary glucose level a minimum of 21 times in a 7-day period).
次要结局
未报告次要终点