Abstract: SA-OR082
Safety and Preliminary Efficacy Findings from a Phase 2A Randomized, Double-Blind, Placebo-Controlled Trial of Setanaxib in Patients with Alport Syndrome
Session Information
- High-Impact Clinical Trials - 2
November 08, 2025 | Location: Hall A, Convention Center
Abstract Time: 10:30 AM - 10:45 AM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits
Authors
- Gale, Daniel P., University College London, London, United Kingdom
- Agraz Pamplona, Irene, Vall d'Hebron Institute of Research, Barcelona, Spain
- Arslan, Zainab, Great Ormond Street Hospital for Children, London, United Kingdom
- Esteban de la Rosa, Rafael José, Hospital Universitario Virgen de las Nieves, and Instituto de Investigación Biosanitaria ibs, Granada, Spain
- Hall, Matthew, Nottingham University Hospitals, Nottingham, United Kingdom
- Krejci, Karel, University Hospital and Faculty of Medicine Palacký University Olomouc, Olomouc, Czechia
- Morales, Enrique, Hospital Universitario 12 de Octubre, Madrid, Spain
- Safranek, Roman, Charles University and University Hospital Hradec Kralove, Hradec Kralove, Czechia
- Tesar, Vladimir, General University Hospital, Charles University, Prague, Czechia
- Torra, Roser, Fundació Puigvert, Institut de Recerca Sant Pau (IR-Sant Pau), Departament de Medicina, Universitat Autònoma de Barcelona, RICORS2040 renal, Barcelona, Spain
- Viklicky, Ondrej, Institute for Clinical and Experimental Medicine, Prague, Czechia
- Carlsson, Carl Stefan, Calliditas Therapeutics AB, Stockholm, Sweden
- Levine, Aaron, Calliditas Therapeutics AB, Stockholm, Sweden
- Lennon, Rachel, Royal Manchester Children’s Hospital, Manchester, United Kingdom
Background
Alport syndrome (AS) is a rare genetic disease resulting in collagen IV abnormalities and is marked by interstitial fibrosis and declining kidney function. Fibrosis prevention may preserve kidney function. We report safety and preliminary efficacy findings with setanaxib, an enzyme-driven hydrogen peroxide-depleting agent with anti-fibrotic properties, in patients (pts) with AS.
Methods
In this Phase 2a trial (NCT06274489), 20 pts (12–40 years) with genetically confirmed AS, UPCR ≥0.8 g/g, eGFR ≥30 mL/min/1.73 m2 and at risk of disease progression despite background therapy were randomized 2:1 to receive oral setanaxib (seta; 800 mg BID [18–40 years]/800 + 400 mg/day [12–17 years]; n=13) or placebo (pbo; n=7) plus background therapy for 24 weeks (wks). Primary endpoints were serious adverse events (SAEs) and AEs of special interest (AESIs); secondary endpoints included changes in UPCR and eGFR from baseline. After 24 wks, pts were followed for 4 wks on background therapy alone. Of the background therapies allowed, 16 pts were on ACEis (11 seta, 5 pbo), 11 on SGLT2is (7 seta, 4 pbo) and 10 on both (7 seta, 3 pbo).
Results
One randomized pt in the pbo group withdrew consent before treatment start. AEs occurred at similar frequencies in both treatment groups. Primary endpoints were met: 1 seta group pt had an SAE of acute cholecystitis that was not deemed treatment related by the investigator, and no AESIs were reported. The seta group had a 15% mean UPCR reduction at 24 wks vs pbo. Two (15.4%) seta group pts had a UPCR reduction of ≥25% from baseline at 24 wks, vs none in the pbo group. An ad hoc analysis showed that 5 (38.5%) seta group pts had a UPCR reduction of ≥10% vs baseline, vs 1 (16.7%) pbo group pt. The seta group also had a 27% mean UPCR reduction at 4 wks post dosing vs pbo. There was a 5% mean reduction in eGFR with seta vs pbo at 24 wks and a 4% reduction at 4 wks post dosing.
Conclusion
In pts with AS, setanaxib plus background therapy had an acceptable safety profile with a trend towards UPCR reduction after 24 wks of dosing and at 4 wks post dosing vs background therapy alone.
Funding
- Commercial Support – Calliditas Therapeutics