Abstract: SA-PO902
Sparsentan and Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) in the PROTECT Open-Label Extension (OLE) Substudy and SPARTACUS: Trials in Progress
Session Information
- Glomerular Diseases: Therapeutics
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Ayoub, Isabelle, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Komers, Radko, Travere Therapeutics Inc, San Diego, California, United States
- Mercer, Alex, JAMCO Pharma Consulting, Stockholm, Sweden
- Preciado, Priscila, Travere Therapeutics Inc, San Diego, California, United States
- Tang, Sydney C.W., The University of Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong
- Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background
Sparsentan (SPAR) is a nonimmunosuppressive, single-molecule, dual endothelin and angiotensin II receptor antagonist (DEARA). In the phase 3 PROTECT study, SPAR is compared to active control irbesartan in patients with immunoglobulin A nephropathy (IgAN). Subgroup analyses from the DAPA-CKD and EMPA-KIDNEY studies indicate SGLT2i reduce the risk of progression to kidney failure in patients with IgAN. The combination of SGLT2i and DEARA may provide therapeutic benefit due to potentially additive kidney protection. The double-blind period of PROTECT did not permit SGLT2i; however, an OLE substudy has been initiated which randomizes patients on stable SPAR to SGLT2i or no SGLT2i. The ongoing SPARTACUS study allows patients on stable SGLT2i to receive SPAR. These studies will evaluate the safety and effect of concomitant SPAR and SGLT2i in patients with IgAN.
Methods
The PROTECT OLE substudy is investigating the safety and effect of SGLT2i add-on with SPAR as compared to SPAR alone in patients with IgAN. SPARTACUS is a phase 2 study of SPAR safety and effect in IgAN patients on a stable dose of an SGLT2i. The Figure reports study designs and relevant inclusion criteria.
Results
The PROTECT OLE substudy and SPARTACUS safety and effect endpoints are reported in the Table, and results from these studies may be expected by late 2024 and early 2025, respectively.
Conclusion
The PROTECT OLE substudy and SPARTACUS study will evaluate the safety and effect of concomitant SPAR and SGLT2i in patients with IgAN.
Table. PROTECT OLE Substudy and SPARTACUS Endpoints
| Endpoints | PROTECT OLE Substudy | SPARTACUS |
| Safety endpoints | TEAEs | TEAEs SAEs AEs leading to treatment discontinuation AEs of interest |
| Primary effect endpoints | Mean change from baseline in UP/C and UA/C at Week 12 Achievement of urinary protein excretion <0.3 g/day at Week 12 Change in absolute and percent change from baseline in eGFR at Week 12 | Change from baseline in UA/C at Week 24 |
| Secondary effect endpoint | - | Achievement of UA/C <0.2 g/g at Week 24 |
| AE, adverse event; BP, blood pressure; eGFR, estimated glomerular filtration rate; SAE, serious adverse event; TEAE, treatment-emergent adverse event; UA/C, urine albumin to creatinine ratio; UP/C, urine protein to creatinine ratio. | ||
Funding
- Commercial Support – Travere Therapeutics, Inc.