🎯 BACKGROUND

• Focal segmental glomerulosclerosis (FSGS) is a major cause of kidney failure worldwide, with no approved treatments
• Angiotensin II and endothelin-1 play crucial roles in glomerular injury, leading to proteinuria and kidney damage in FSGS
• Inhibitors of the renin-angiotensin-aldosterone system (RAAS) and endothelin-1 receptor antagonists can effectively reduce proteinuria
• Sparsentan, a novel dual endothelin-angiotensin receptor antagonist, has shown promising results in clinical trials
• In the phase 2 DUET trial, sparsentan demonstrated superior efficacy in reducing proteinuria compared to irbesartan after 8 weeks
• This 108-week, randomized, phase 3 clinical trial comparing sparsentan with irbesartan in FSGS patients has been conducted to assess long-term efficacy and safety

🔎 METHODOLOGY

TRIAL DESIGN

• Multicenter, double-blind trial comparing sparsentan with irbesartan in FSGS patients
• Eligibility criteria:
  • Age: 8 to 75 years
  • Biopsy-confirmed FSGS or documented pathogenic variant in podocyte protein
  • Urinary protein-to-creatinine ratio ≥1.5
  • eGFR ≥30 ml/min/1.73 m²
• Exclusion: FSGS resulting from other causes
• 2-week washout period for patients on RAAS inhibitors
• Randomization:
  • 1:1 ratio: sparsentan (800 mg/day) vs. irbesartan (300 mg/day)
  • Duration: up to 108 weeks
  • Stratified by urinary protein-to-creatinine ratio and eGFR
• Final visit: Week 112 (4 weeks post-treatment)
• Trial oversight: Designed and funded by Travere Therapeutics

EFFICACY END POINTS

• Surrogate efficacy end point (36-week interim analysis): FSGS partial remission of proteinuria
  • Defined as urinary protein-to-creatinine ratio ≤1.5 and >40% reduction from baseline
  • Chosen for its ability to predict kidney function preservation and long-term outcomes
• Primary end point: eGFR slope (rate of change in eGFR per year)
  • Selected as a predictor of progression to kidney failure
  • Total eGFR slope: Day 1 to Week 108 (primary in US, secondary outside US)
  • Chronic eGFR slope: Week 6 to Week 108 (primary outside US, secondary in US)