Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study.
DUPLEX, the largest interventional FSGS trial to date, enrolled 371 biopsy-proven or genetically defined FSGS patients to test the dual endothelin–angiotensin receptor antagonist sparsentan against irbesartan, establishing a geographically and clinically diverse baseline population.
Background
Focal segmental glomerulosclerosis (FSGS) frequently progresses to end-stage kidney disease and lacks approved targeted therapies. Sparsentan is a novel, non-immunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist (DEARA) being evaluated for its antiproteinuric and nephroprotective potential. DUPLEX (NCT03493685) is the largest interventional study in FSGS conducted to date.
Study design
DUPLEX is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study comparing sparsentan 800 mg once daily with irbesartan 300 mg once daily. Eligible patients were aged 8 to 75 years (USA/UK) or 18 to 75 years elsewhere, weighing at least 20 kg, with biopsy-proven FSGS or a documented podocyte-protein genetic mutation and a urine protein-to-creatinine ratio (UP/C) of 1.5 g/g or higher. The primary analysis population comprised 371 patients (336 adults and 35 pediatric).
Key findings
The enrolled population had a median age of 42 years and was predominantly White (73.0%), with Asian (13.2%), Black/African American (6.7%), and Other (7.0%) participants drawn from North America, Europe, South America, and Asia Pacific. Baseline median UP/C was 3.0 g/g, with 42.6% in the nephrotic range, and patients were distributed across eGFR categories corresponding to CKD stages 1 to 3b. Genetic analysis identified pathogenic or likely pathogenic podocyte gene variants in 9.4% of evaluable samples, collagen (COL4) variants in 7.7%, and APOL1 high-risk genotypes in 4.0%.
Clinical implications
By characterizing a large, geographically broad, and clinically diverse FSGS cohort, DUPLEX enables robust assessment of the treatment effect of dual endothelin–angiotensin receptor blockade across both primary and genetic forms of FSGS. The detailed baseline profile, including genetic subgroups often resistant to conventional therapy, supports interpretation of the trial's subsequent efficacy and safety outcomes.
Category
Research
Source
Kidney Int Rep
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