POS-452 SAFETY AND EFFICACY OF ANG-3070 IN PATIENTS WITH PRIMARY PROTEINURIC KIDNEY DISEASE: A PHASE 2 STUDY DESIGN

Abstract

Primary proteinuric kidney diseases (PPKDs) are among the leading causes of end-stage kidney disease (ESKD). Receptor tyrosine kinases, including platelet-derived growth factor receptor and discoidin domain receptors 1 and 2, are thought to play a role in the progression of PPKDs to ESKD. ANG-3070, a selective oral tyrosine kinase inhibitor, has demonstrated beneficial effects in chronic kidney disease animal models. Here we describe the design of a proof-of-concept study of ANG-3070 in the treatment of patients with PPKD who have persistent proteinuria while on standard of care (SOC). Planned enrollment is 100 patients for this 12-week, randomized, double-blind, placebo-controlled study. Eligible patients have biopsy-proven PPKD and persistent proteinuria (≥1 g/day) while on SOC, which may include maximum tolerated RAAS inhibitors. Patients will be randomized 1:1:1:1 to ANG-3070 200 mg or 400 mg once daily, or 300 mg twice daily, or placebo (Figure). The primary endpoint is the percentage change in 24-hr urinary protein at Week 12 compared to baseline. Key secondary endpoints evaluated at Week 12 include percentage change in 24-hr urinary albumin, number of patients with complete remission in proteinuria (24-hr urinary protein <300 mg), number of patients with partial remissions in proteinuria (24-hr urinary protein reduction of ≥50% from baseline and a 24-hr urinary protein <3.5 g if baseline 24-hr urinary protein >3.5 g), number of patients with ≥50% reduction in 24-hr urinary protein from baseline, and number of patients with ≥50% reduction in 24-hr urinary albumin from baseline. An independent data monitoring committee will review safety throughout the study. Enrollment will begin in 2021. This phase 2 study will provide data about the safety and efficacy of different dosing regimens of ANG-3070 in PPKD patients that will inform the design of a phase 3 study.