#3318 PHASE II DOSE-SELECTION, RANDOMISED DOUBLE-BLIND TRIAL OF THE ASI, BI 690517, ALONE AND IN COMBINATION WITH EMPA IN PEOPLE WITH CKD

Abstract Background and Aims Elevated aldosterone levels are associated with chronic kidney disease (CKD) progression and adverse kidney and cardiovascular disease outcomes. Therapy with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) improves clinical outcomes, yet elevated aldosterone levels often persist. BI 690517 is a first-in-class, selective aldosterone synthase inhibitor (ASi) that may reduce deleterious mineralocorticoid receptor-dependent and -independent actions of aldosterone. Coadministration of BI 690517 with a sodium–glucose cotransporter-2 inhibitor could mitigate the risk of hyperkalaemia. This study is investigating the efficacy and safety of three doses of BI 690517, alone and in combination with empagliflozin (EMPA), on top of an ACEi or ARB, for treatment of CKD with or without type 2 diabetes. Method A randomised, double-blind, placebo-controlled, parallel-dose Phase II trial (NCT05182840) in adults with or without type 2 diabetes who had an estimated glomerular filtration rate (eGFR) ≥30 and <90 mL/min/1.73 m2, urine albumin:creatinine ratio (UACR) ≥200 and <5000 mg/g, and serum potassium ≤4.8 mmol/L on stable background therapy with an ACEi or ARB. After an 8-week run-in period to assigned background therapy (EMPA 10 mg or matched placebo randomised 1:1), participants were randomised 1:1:1:1 to BI 690517 (low, medium or high dose) or matched placebo for 14 weeks. Primary outcome was the change in UACR measured in a first morning void (UACRFMV) from baseline to Week 14. Secondary outcomes were the proportion of participants with ≥15 and 30% decreases in UACRFMV. Safety outcomes and changes in eGFR and serum potassium were also evaluated. Results Recruitment is complete, with 1719 participants from 168 sites in 29 countries screened. In total, 714 were randomised and entered the run-in period (last randomisation on 30 December 2022). The trial is currently ongoing; data on baseline characteristics will become available and shared. Conclusion This study will provide key data on the potential synergistic kidney-protective effects and safety of combination therapy with BI 690517 plus EMPA, as well as data on monotherapy, for CKD with or without type 2 diabetes. Findings will inform BI 690517 dose selection for further clinical trial development.