Abstract: PO1980
Sparsentan for Treatment of Pediatric Patients with Selected Proteinuric Glomerular Diseases: Design of the Phase 2 EPPIK Study
Session Information
- Pediatric Nephrology: AKI, Dialysis, Transplant, CKD, and Nephrotic Syndrome
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1700 Pediatric Nephrology
Authors
- Trachtman, Howard, NYU School of Medicine, New York, New York, United States
- Saleem, Moin, University of Bristol & Bristol Royal Hospital for Children, Bristol, United Kingdom
- Coppo, Rosanna, Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
- Rheault, Michelle N., University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
- He, Ping, Travere Therapeutics Inc, San Diego, California, United States
- Komers, Radko, Travere Therapeutics Inc, San Diego, California, United States
Background
Sparsentan is a novel Dual Endothelin Angiotensin Receptor Antagonist (DEARA) being investigated for focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN). It is a dual acting, highly selective antagonist of both the endothelin A receptor (ETAR) and the angiotensin II subtype 1 receptor (AT1R). The Phase 2 EPPIK study will examine the long-term antiproteinuric and nephroprotective potential and safety of sparsentan in pediatric patients with FSGS, minimal change disease (MCD), IgAN, IgA vasculitis (IgAV), and Alport syndrome (AS).
Methods
The global, open-label, single-arm, multicenter study will evaluate the safety, efficacy, and pharmacokinetics (PK) of sparsentan in ~57 patients (aged ≥1 to <18 years), including ~30 with FSGS and/or MCD (population 1) and ~27 with IgAN, IgAV, or AS (population 2) over 108 weeks (Figure). See Table for inclusion/exclusion criteria. Sparsentan will be administered in a novel liquid formulation at a dose adjusted to body weight.
Results
Primary endpoints include safety (incidence of treatment-emergent adverse events) and change in urine protein/creatinine ratio (UP/C) from baseline over 108 weeks of sparsentan treatment. Secondary endpoints include PK outcomes, change from baseline over 108 weeks in albumin/creatinine ratio and eGFR, and the proportion of patients with FSGS/MCD who achieve partial remission (UP/C ≤1.5 g/g and >40% reduction in UP/C).
Conclusion
This Phase 2 study will evaluate the long-term safety, antiproteinuric, and nephroprotective effects of sparsentan in pediatric patients.
Table. Key Inclusion and Exclusion Criteria
| Inclusion All: eGFR ≥30 mL/min/1.73m2; mean seated blood pressure 5th to 95th percentile for age/sex/height |
| Population 1: Male/female age ≥1 and <18 years; UP/C ≥1.5 g/g at screening despite history or ongoing corticosteroid/immunosuppressive drugs; biopsy-proven FSGS/MCD or FSGS/MCD-associated genetic mutation in a podocyte protein |
| Population 2: Male/female age ≥2 and <18 years; UP/C ≥1.0 g/g at screening; biopsy-confirmed IgAN/IgAV nephritis or AS-associated genetic mutation |
| Exclusion All: Weighs <7.3 kg at screening; secondary FSGS/MCD/IgAN/IgAV; significant cardiovascular or hepatic conditions; new immunosuppressive therapy within 6 months of screening or not on stable dose of chronic therapy ≥1 month before screening |
Funding
- Commercial Support –