Clinical trial NCT01613118
Conditions: Focal Segmental Glomerulosclerosis
Keywords: Primary FSGS Nephrotic syndrome Steroid Resistant
Sponsor: Travere Therapeutics, Inc.
Start date: 2014-03-01; Completion date: 2024-03-25
Enrollment: 109 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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).

Detailed description:
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.

Arms: arm 1: 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. arm 2: 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. arm 3: 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. arm 4: 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. arm 5: 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.
Interventions: intervention 1: RE-021 (Sparsentan) intervention 2: Irbesartan
Intervention descriptions: intervention 1: Oral, once-daily intervention 2: Oral, once-daily

Protocol documents: