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Kidney Week

Abstract: FR-OR109

Pivotal Results of the Phase 3 PROTECT Trial of Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients with Immunoglobulin A Nephropathy (IgAN)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Rovin, Brad H., Division of Nephrology, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
  • Diva, Ulysses, Travere Therapeutics, San Diego, California, United States
  • Komers, Radko, Travere Therapeutics, San Diego, California, United States
  • Perkovic, Vlado, University of New South Wales Sydney, Sydney, New South Wales, Australia

Group or Team Name

  • On behalf of the DUPRO steering committee and PROTECT investigators
Background

SPAR, a dual endothelin angiotensin receptor antagonist (DEARA), showed a significantly greater reduction in urine protein excretion vs IRB in patients (pts) with biopsy-proven IgAN in an interim 36-wk analysis of the PROTECT trial (−49.8% vs −15.1%, respectively; P<.0001) (Heerspink et al. Lancet. 2023). Based on these data, SPAR was granted accelerated approval in the US for adults with primary IgAN at risk of rapid disease progression. We will present the pivotal double-blind PROTECT trial results on the efficacy and safety of SPAR vs IRB. These results will be available after database lock in Sep 2023.

Methods

PROTECT is a phase 3, international, randomized, double-blind, parallel-group, active-controlled trial evaluating the efficacy and safety of SPAR vs IRB in adults with IgAN at high risk of progression to kidney failure despite maximized treatment with an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker. Pts with biopsy-proven IgAN, urine protein excretion ≥1.0 g/d, and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 were randomized 1:1 to SPAR 400 mg/d or IRB 300 mg/d for up to 110 wk. The final analysis will report the 2-year rate of eGFR change (chronic and total slope), kidney composite endpoint (rate of >40% eGFR decline, kidney failure, or death), change in proteinuria by visit, rates of complete (<0.3 g/d) and partial (<1.0 g/d) proteinuria remission, and long-term safety and tolerability. Analyses used will be a mixed model random coefficients analysis (eGFR slope), mixed model for repeated measures (change in proteinuria), and logistic regression model (remission and composite endpoints).

Results

A total of 404 pts were randomized to SPAR (n=202) or IRB (n=202). We will present eGFR chronic and total slopes over 2 years, incidence of the kidney composite endpoint, percent change from baseline in urine protein-creatinine ratio through wk 110, and proportion of pts who achieved complete or partial proteinuria remission at any time within 110 wk. Safety and tolerability data will be presented.

Conclusion

The phase 3 trial results on kidney function and outcomes, proteinuria, and safety with SPAR vs IRB over 2 years may significantly impact the treatment landscape of pts with IgAN.

Funding

  • Commercial Support – Travere Therapeutics