Abstract BACKGROUND AND AIMS Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease worldwide. Despite optimized standard of care treatment, up to 40% of individuals with IgAN develop kidney failure requiring dialysis or kidney transplantation, consequently seriously affecting their quality of life and mortality. Treatments that reduce proteinuria and risk of kidney disease progression are urgently needed for IgAN. Sparsentan is a novel Dual Endothelin Angiotensin Receptor Antagonist (DEARA) being investigated for IgAN. The Phase 3 PROTECT study is examining the potential long-term antiproteinuric and nephroprotective potential and safety of sparsentan compared with an active control, angiotensin receptor blocker (ARB) irbesartan, in adults with IgAN. Here we report the baseline characteristics for all patients enrolled in the PROTECT trial. METHOD PROTECT is an ongoing, global, Phase 3, multicenter, randomized, double-blind, parallel-group, active controlled study designed to evaluate the efficacy and safety of sparsentan versus the active control irbesartan in adults with IgAN with overt proteinuria despite receiving maximized treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or ARB. The study duration is 270 weeks: a double-blind period of 114 weeks followed by an open-label extension period of up to 156 weeks. The primary efficacy endpoint is the change from baseline in urine protein/creatinine ratio (UP/C) based on a 24-h urine sample at Week 36. Key inclusion and exclusion criteria are shown in Table 1. Patients took their last dose of maximized standard-of-care treatment with ACEi and/or ARB therapy the day before randomization. Patients were randomized 1:1 to sparsentan or irbesartan (target dose 400 and 300 mg/day, respectively), stratified by screening eGFR and urine protein excretion values. The blinded and aggregated baseline characteristics of all the patients enrolled in the PROTECT trial are summarized descriptively. RESULTS A total of 406 patients from clinical sites in 18 countries, including sites in North America, Europe and Asia Pacific, were enrolled in PROTECT and 404 patients were included in the primary analysis population. Selected demographic and clinical characteristics are reported in Table 2. CONCLUSION PROTECT is the largest interventional trial testing a novel drug to date in IgAN. Patients with IgAN enrolled in the PROTECT trial display demographic and clinical characteristics consistent with those previously reported in the broader high-risk IgAN patient population. The presentation despite implementation of optimized standard of care treatment demonstrates the burden of IgAN and the unmet need for novel therapies in this patient population.