Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study
Year: 2024
Type: article
Abstract: Introduction The phase 3 DUPLEX trial is evaluating sparsentan, a novel, non-immunosuppressive, 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 8-75 years (USA/UK) and 18-75 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/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 eGFR categories corresponding to chronic kidney disease stages 1-3b. 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.
Source: Kidney International Reports
Authors: 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
Institutions: University of Michigan, Michigan Medicine, Columbia University, University of Minnesota, University of Washington, University of Leicester, Leicester General Hospital, University Medical Center Groningen, University of Groningen, The George Institute for Global Health, Universidade de São Paulo, UNSW Sydney, The Ohio State University Wexner Medical Center, Hospital Británico de Buenos Aires, The University of Sydney, Travere Therapeutics (United States)
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
OpenAlex ID: W4391290112