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

Summary

The sparsentan Phase 3 DUPLEX trial was the largest interventional focal segmental glomerulosclerosis (FSGS) trial to date¹*

Background

Focal segmental glomerulosclerosis (FSGS) is defined as a histological lesion characterized by segmental accumulation of the glomerular extracellular matrix.² This results in capillary obliteration and glomerular scarring.²

Patients with FSGS often present with nephrotic syndrome and a varying degree of proteinuria.² Patients with FSGS are typically treated with renin angiotensin system inhibitors (RASi) in combination with immunosuppressive regimens.^3,4 But there is still an unmet need for more tolerable and effective treatments.⁵

Sparsentan is a non-immunosuppressive, single-molecule dual endothelin and angiotensin receptor antagonist.^6,7

Aim

The objective of the Phase 3 DUPLEX study was to evaluate the long-term efficacy and safety of sparsentan compared with the active comparator irbesartan in FSGS.¹ This manuscript aims to describe the baseline characteristics of the enrolled patients.¹

Read more about the efficacy and safety findings from the DUPLEX trial and its post hoc analyses of proteinuria thresholds and the effect on progression to kidney failure.

Approach

DUPLEX was a large, international, randomized, double-blind, interventional Phase 3 study of sparsentan in FSGS.¹ Patients were randomized to receive sparsentan 800 mg or irbesartan 300 mg.¹ Key eligibility criteria included¹:

Those with a known secondary cause of FSGS or serological test findings diagnostic of another primary or secondary glomerular disease were excluded.¹

Baseline characteristics were analyzed, including by race and geographic region.¹ Evaluating by race and geography may help characterize differences in FSGS presentation.¹ Analysis also included genotype testing and mapping of pathogenic variants in podocyte proteins associated with FSGS.¹

Findings

Demographic and clinical baseline characteristics

The enrolled population (N=371) primarily consisted of White adults (73%, 271/371) from North America (38.8%, 144/371) and Europe (36.1%, 134/371) with a median age of 42 years (range: 27.0-56.0).¹

The median age at diagnosis was 37 years (interquartile range: 23.0-51.0).¹ Key baseline clinical and laboratory assessments included¹:

There was a wide distribution across eGFR ranges corresponding to chronic kidney disease (CKD) stages 1 to 3b.¹

Clinical and laboratory findings varied by race and geographic regions.¹

Genetic baseline characteristics

Of the 352 patients with evaluable samples, 9.4% (33/352) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function.¹

P/LP variants of collagen genes were identified in 7.7% (27/352) of patients, and 4.0% (14/352) of patients had APOL1 high risk variants.¹

Key takeaway

Baseline characteristics were geographically broad and clinically diverse.¹ The sparsentan phase 3 DUPLEX trial identified the treatment effect of sparsentan across a heterogeneous FSGS patient population.¹

Footnotes

Sparsentan is not FDA-approved for the treatment of FSGS.

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; FDA, Food and Drug Administration; FSGS, focal segmental glomerulosclerosis; P/LP, pathogenic or likely pathogenic; RASi, renin angiotensin system inhibitor; UPCR, urine protein-to-creatinine ratio.

*As of July 2024.

MA-SP-24-0055 | June 2025