Abstract: FR-OR108
Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients with Focal Segmental Glomerulosclerosis (FSGS): Results from the Phase 3 DUPLEX Trial
Session Information
- High-Impact Clinical Trials
November 03, 2023 | Location: Hall A, Pennsylvania Convention Center
Abstract Time: 10:30 AM - 10:45 AM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Rheault, Michelle N., University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Trachtman, Howard, University of Michigan, Ann Arbor, Michigan, United States
- Diva, Ulysses, Travere Therapeutics, San Diego, California, United States
- Komers, Radko, Travere Therapeutics, San Diego, California, United States
Group or Team Name
- On behalf of the DUPRO steering committee and DUPLEX investigators.
Background
SPAR is a dual endothelin angiotensin receptor antagonist (DEARA) that reduced proteinuria in patients with FSGS in the phase 2 DUET trial. DUPLEX evaluated the antiproteinuric and nephroprotective potential of SPAR vs active control IRB in patients with FSGS. DUPLEX met its interim efficacy endpoint (FSGS partial remission endpoint [FPRE]), with 42% of patients achieving FPRE with SPAR vs 26% with IRB at 36 wk. Here, we present results from the primary analysis.
Methods
In this phase 3 randomized trial, patients (ages 8-75 y) with FSGS, excluding secondary causes, with a urine protein/creatinine ratio (UP/C) ≥1.5 g/g and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 at screening were randomized 1:1 to SPAR or IRB (target dose, 800 and 300 mg/d, respectively) for 108 wk. The primary endpoint was eGFR slope. Other efficacy endpoints are listed in the Table. Safety was assessed and evaluated by a data monitoring committee.
Results
371 patients were randomized to SPAR (n=184) or IRB (n=187). After 108 wk, SPAR showed a 50% reduction in UP/C vs 32% with IRB, with more than twice as many patients achieving complete remission of proteinuria (Table). The differences in eGFR total and chronic slope for SPAR vs IRB were 0.3 and 0.9 mL/min/1.73 m2 per year (P>.05). Additional efficacy results are listed in the Table. SPAR was well tolerated, with a safety profile comparable to IRB.
Conclusion
In the largest randomized trial in FSGS to date, SPAR achieved a clinically meaningful reduction in proteinuria, although the eGFR slope–based primary endpoints were not met. Overall, results support the potential clinical benefit of SPAR for FSGS. Dr Rheault and Dr Trachtman contributed equally.
Funding
- Commercial Support – Travere Therapeutics