Calliditas Therapeutics (Calliditas), an Asahi Kasei company, announced that primary safety endpoints of a Phase 2a, randomized, double-blind, placebo-controlled trial of setanaxib in patients with Alport syndrome were presented in a High-Impact Clinical Trials session at the American Society of Nephrology Kidney Week in Houston, Texas, on Saturday, November 8. Alport syndrome is a rare genetic kidney disease resulting from mutations in collagen type IV genes that can lead to progressive loss of kidney function and end-stage kidney disease. This Phase 2a trial (NCT06274489) enrolled 20 patients aged 12-40 years with genetically confirmed Alport syndrome, a urine protein-creatinine ratio (UPCR) of 0.8 g/g, and an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m2. Patients were randomized 2:1 to receive oral setanaxib (800 mg BID [18-40 years]/800 + 400 mg/day [12-17 years, n=13; or placebo, n=7) plus background therapy for 24 weeks, with a four-week follow-up period on background therapy alone.
The primary endpoints were serious adverse events (SAEs) and adverse events of special interest (AESIs); secondary endpoints included the change in UPCR and eGFR from baseline. The primary safety endpoints were met with AEs occurring at similar frequencies in both treatment groups, and no AESIs were reported. One SAE was reported for a patient in the setanaxib group that was not deemed treatment-related.
Patients receiving setanaxib had a 15% mean reduction in UPCR at 24 weeks and a 27% mean reduction in UPCC at four weeks post-dosing compared to placebo. At Week 24, two patients (15.4%) in the setanaxib Group achieved a 25% reduction in UPCR from baseline, compared with none in the placebo group. There was a 5% mean reduction in eGFR with setanaxib at 24 weeks and a 4% reduction at four weeks post-dosed versus placebo.
Further research is needed to investigate setanaxib's clinical efficacy and confirm its benefit/risk profile in a larger Alport syndrome patient population.
