Sparsentan
Sparsentan is a novel single-molecule dual endothelin (ET-1) and angiotensin receptor antagonist with hemodynamic and anti-inflammatory properties. Overproduction of ET-1 leads to glomerulosclerosis and interstitial fibrosis. ET-1 receptor inhibition is thought to limit the inflammatory, prosclerotic and fibrinogenic actions of ET-1. Sparsentan is now approved by the US Food and Drug Administration for the treatment of adults with IgAN at risk of rapid disease progression and is being investigated for FSGS.
Enroll in this clinical study
How is Spartsentan being studied in FSGS?
In a phase 3 RCT (DUPLEX) of efficacy and safety of longer-term treatment with sparsentan among patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan.
EPPIK is a Phase 2, Open-Label, Single-Arm, Cohort Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Sparsentan Treatment in Pediatric Subjects With Selected Proteinuric Glomerular Diseases.
This is a multicenter, open-label, 112-week study of sparsentan in approximately 67 pediatric subjects aged ≥1 year to <18 years with selected proteinuric glomerular diseases, divided into 3 populations, defined as follows:
Population 1: Subjects with selected proteinuric glomerular diseases associated with FSGS) and Minimal Change Disease (MCD) histological patterns -800 mg Sparsentan oral suspension.
Population 2: Subjects with kidney biopsy-confirmed IgAN, immunoglobulin A vasculitis (IgAV), or Alport syndrome (AS) - 400 mg Sparsentan oral suspension
Population 3: Subjects with kidney biopsy-confirmed IgAN - 400 mg Sparsentan tablets
The primary outcomes of measure are incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), AEs leading to treatment discontinuation, adverse events of interest (AEOIs) and Urine protein/creatinine ratio (UP/C) at week 108.
Eligibility Criteria
Inclusion Criteria for All Subjects (All Three Populations):
A subject must meet all of the following criteria :
The subject or parent/legal guardian is willing and able to provide signed informed consent/assent.
eGFR ≥30 mL/min/1.73 m2 at screening.
mean seated BP between the 5th and 95th percentile for sex and height.
Population 1:
Age ≥1 year at screening and <18 years of age at Day 1
UP/C ≥1.5 g/g (170 mg/mmol) at screening AND one of the following:
Kidney biopsy-proven FSGS or MCD and clinical presentation consistent with primary FSGS or MCD and qualifying proteinuria at screening despite history or ongoing treatment with corticosteroids and/or other immunosuppressive disease-modifying agents.
Documentation of a genetic mutation in a podocyte protein associated with FSGS or MCD.
Kidney biopsy-proven FSGS histological pattern with medical history and clinical presentation consistent with maladaptive cause of the lesion.
Population 2:
Age ≥2 years at screening and <18 years of age at Day 1.
UP/C ≥0.6 g/g (68 mg/mmol) at screening AND one of the following diagnoses:
Kidney biopsy-confirmed IgAN, IgAV, or AS
Diagnosis of AS by genetic testing
Population 3:
age ≥8 years at screening and <18 years of age at Day 1.
UP/C ≥1.0 g/g (113 mg/mmol) at screening AND has kidney biopsy-confirmed IgAN
weight ≥40 kg
Already on ACEI and/or ARB therapy for at least 12 weeks prior to screening
Link to Study website: