Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis

Phase 2

Completed

• Conditions: Focal Segmental Glomerulosclerosis
• Interventions: Drug: RE-021 (Sparsentan); Drug: Irbesartan

• Registration Number: NCT01613118
• Lead Sponsor: Travere Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2012-06-04
• Study First Submitted QC: 2012-06-05
• Study First Posted: 2012-06-06
• Study Start: 2014-03
• Primary Completion: 2016-06
• Results First Submitted: 2020-12-10
• Results First Submitted QC: 2021-07-06
• Results First Posted: 2021-07-27
• Study Completion: 2024-03-25
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 109

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RE-021 (Sparsentan) 200 mg - Double-Blind Period	RE-021 (Sparsentan)	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.
RE-021 (Sparsentan) 400 mg - Double-Blind Period	RE-021 (Sparsentan)	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.
RE-021 (Sparsentan) 800 mg - Double-Blind Period	RE-021 (Sparsentan)	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.
Irbesartan 300 mg - Double-Blind Period	Irbesartan	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.
RE-021 (Sparsentan) - Open-Label Extension Period	RE-021 (Sparsentan)	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.

Primary Outcome Measures

Name	Time	Method
Percent Change in Urine Protein/Creatinine (Up/C)	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Achieving FSGS Partial Remission Endpoint (FPRE)	8 weeks	The secondary efficacy endpoint is the proportion of FSGS patients achieving FPRE (experiencing a UP/C ratio ≤1.5 g/g and \>40% reduction from baseline in Up/C) at Week 8 over a range of dose levels compared to treatment with irbesartan as active control.

Trial Locations

Locations (33)

Temple University School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Marshfield Clinic Research Foundation; 🇺🇸 Marshfield, Wisconsin, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Clinical Advancement Center; 🇺🇸 San Antonio, Texas, United States

Los Angeles Biomedical Research Institute; 🇺🇸 Torrance, California, United States

Balboa Nephrology Medical Group; 🇺🇸 San Diego, California, United States

University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States

Miami Children's Hospital; 🇺🇸 Miami, Florida, United States

University of Iowa Children's Hospital; 🇺🇸 Iowa City, Iowa, United States

Renal and Transplant Associates of New England, PC; 🇺🇸 Springfield, Massachusetts, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

SUNY Stony Brook Hospital; 🇺🇸 Stony Brook, New York, United States

Akron Nephrology Associates; 🇺🇸 Akron, Ohio, United States

The Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Northeast Clinical Research Center; 🇺🇸 Bethlehem, Pennsylvania, United States

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pennsylvania, Perelman School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Southern Utah Kidney and Hypertension Center; 🇺🇸 Saint George, Utah, United States

Catholic Health Initiatives Franciscan; 🇺🇸 Tacoma, Washington, United States

General Teaching Hospital Prague; 🇨🇿 Prague, Czechia

NYU Langone Medical Center; 🇺🇸 New York, New York, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Azienda Ospedaliero Universitaria Policlinico di Bari; 🇮🇹 Bari, Italy

Azienda Ospedaliero Universitaria Careggi; 🇮🇹 Firenze, Italy

IRCCS Istituti Clinici Maugeri; 🇮🇹 Pavia, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Rome, Italy

Colorado Kidney Care; 🇺🇸 Denver, Colorado, United States

The Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

UNC Kidney Center, Pediatrics; 🇺🇸 Chapel Hill, North Carolina, United States

University North Carolina (UNC) Kidney Center; 🇺🇸 Chapel Hill, North Carolina, United States

Unversity of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States