Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients With Focal Segmental Glomerulosclerosis (FSGS): a Randomized, Double-Blind, Active-Control, Dose-Escalation Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 109
- 试验地点
- 33
- 主要终点
- Percent Change in Urine Protein/Creatinine (Up/C)
研究概览
简要总结
This study will investigate whether RE-021 (Sparsentan), a selective dual-acting receptor antagonist with affinity for endothelin (A type) and angiotensin II receptors (Type 1), is safe and effective in treating patients with focal segmental glomerulosclerosis (FSGS).
详细描述
Focal segmental glomerulosclerosis (FSGS) is a rare glomerular disorder which results in frank proteinuria and in some patients progression to end-stage kidney disease (ESKD) over 5-10 years. Proteinuria reduction is widely regarded to be beneficial and is considered the primary goal of treatment in FSGS and slowing its progressive course (D'Agati, et. al, 2011). Patients are currently treated with angiotensin receptor blockers (ARB) and angiotensin converting inhibitors (ACEI) to lower proteinuria with steroids, calcineurin inhibitors, and other immunosuppressive agents reserved for patients with severe proteinuria and in particular with nephrotic syndrome. Despite these therapies, many patients have nephrotic range proteinuria and new therapeutic agents are needed. Endothelin receptor antagonists (ERA) have been shown to lower proteinuria in clinical trials of diabetic nephropathy and have been speculated to be effective in FSGS.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 8 Years 至 75 Years（Child, 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
RE-021 (Sparsentan) 200 mg - Double-Blind Period
RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 200mg.
Patients at </= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration.
干预措施: RE-021 (Sparsentan) (Drug)
RE-021 (Sparsentan) 400 mg - Double-Blind Period
RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 400mg.
Patients at </= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration.
干预措施: RE-021 (Sparsentan) (Drug)
RE-021 (Sparsentan) 800 mg - Double-Blind Period
RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 800mg.
Patients at </= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration.
干预措施: RE-021 (Sparsentan) (Drug)
Irbesartan 300 mg - Double-Blind Period
The control will be administered irbesartan as a single oral dose of 150mg for the first week before escalating to 300mg for the remaining 7 weeks.
Patients at </= 50kg will receive 150mg irbesartan for the 8 week duration.
干预措施: Irbesartan (Drug)
RE-021 (Sparsentan) - Open-Label Extension Period
Includes all subjects who completed the Double-Blind period and enrolled in the Open-Label Extension period of the study.
All subjects who completed the Double-Blind period were evaluated for response and safety at the Week 8 visit to determine eligibility for continued treatment on their assigned doses in an Open-Label Extension period for up to 496 additional weeks. Subjects treated with irbesartan during the Double-Blind period were offered sparsentan treatment at the dose they would have received according to the Double-Blind dose cohort in which they were enrolled.
干预措施: RE-021 (Sparsentan) (Drug)
结局指标
主要结局
Percent Change in Urine Protein/Creatinine (Up/C)
时间窗: 8 weeks
Primary efficacy objective is to determine the change in UP/C in FSGS patients receiving RE-021 (Sparsentan) from baseline to 8 weeks over a range of dose levels compared to treatment with irbesartan as active control.
次要结局
- Percentage of Patients Achieving FSGS Partial Remission Endpoint (FPRE)(8 weeks)