Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study

Howard Trachtman, Jai Radhakrishnan, Michelle N. Rheault, Charles E. Alpers, Jonathan Barratt, Hiddo J.L. Heerspink, Irene L. Noronha, Vlado Perkovic, Brad Rovin, Hernán Trimarchi, Muh Geot Wong, Alex Mercer, Jula Inrig, William Rote, Ed Murphy, Patricia W. Bedard, Sandra Roth, Stewart Bieler, Radko Komers

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS). Methods: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics blinded to treatment allocation are reported descriptively. Results: The primary analysis population includes 371 patients (336 adult, 35 pediatric [<18 years]) who were randomized and received study drug (median age, 42 years). Patients were White (73.0%), Asian (13.2%), Black/African American (6.7%), or Other race (7.0%); and from North America (38.8%), Europe (36.1%), South America (12.7%), or Asia Pacific (12.4%). Baseline median UP/C was 3.0 g/g; 42.6% in nephrotic-range (UP/C >3.5 g/g [adults]; >2.0 g/g [pediatrics]). Patients were evenly distributed across estimated glomerular filtration rate (eGFR) categories corresponding to chronic kidney disease (CKD) stages 1 to 3b. Thirty-three patients (9.4% of 352 evaluable samples) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function, 27 (7.7%) had P/LP collagen gene (COL4A3/4/5) variants, and 14 (4.0%) had high-risk APOL1 genotypes. Conclusions: Patient enrollment in DUPLEX, the largest interventional study in FSGS to date, will enable important characterization of the treatment effect of sparsentan in a geographically broad and clinically diverse FSGS population.

Original languageEnglish (US)
Pages (from-to)1020-1030
Number of pages11
JournalKidney International Reports
Volume9
Issue number4
DOIs
StatePublished - Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 International Society of Nephrology

Keywords

  • dual endothelin angiotensin receptor antagonist
  • focal segmental glomerulosclerosis
  • pediatric
  • race
  • randomized controlled clinical trial
  • sparsentan

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