International, randomized, double-blind, active-controlled study (134 sites, 18 countries) which examined sparsentan (400 mg daily) vs irbesartan (300 mg daily) in adults (≥18 years) with biopsy proven IgAN and proteinuria (1 gm/day or higher) despite maximized RAS inhibitor treatment for at least 12 weeks. 404 participants (202 sparsentan and 202 irbesartan) were stratified by eGFR (30 to < 60mL/min or >= 60mL/min) and urine protein excretion (≤ 1.75g/day and > 1.75g/day). Primary endpoint was the change from baseline to week 36 in the urine protein-creatinine ratio based on a 24-hour urine sample. At week 36, there was a statistically significant change from baseline in urine protein-creatinine ratio in the sparsentan group (-49.8%) compared to the irbesartan group (-15.1%); there was a between-group relative reduction of 41%. Treatment-emergent adverse events and safety were similar between irbesartan and sparsentan; once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. A two-year double blind period and its analyses will demonstrate whether or not these effects result in long-term nephroprotective potential of sparsentan.
