Efficacy and safety of balcinrenone and dapagliflozin for CKD: design and baseline characteristics of the MIRO-CKD trial.

Abstract

Background and hypothesis: Despite benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2i) recommended for treatment of chronic kidney disease (CKD), there is still an unmet need for managing renal residual risk. Based on pre-clinical data, balcinrenone is a novel mineralocorticoid receptor antagonist that maintains cardio-renal benefits without increasing hyperkalaemia risk. Use of balcinrenone and dapagliflozin is expected to provide complementary and additive kidney and cardiovascular protection. The MIRO-CKD study tests the hypothesis that balcinrenone with dapagliflozin is superior to dapagliflozin alone in reducing albuminuria in patients with CKD.

Methods: MIRO-CKD is a double-blind, active-controlled, phase 2b study evaluating the efficacy and safety of balcinrenone/dapagliflozin in 300 adults (planned) with CKD, eGFR 25-60 mL/min/1.73m2 and serum potassium within normal range. Participants are being randomized 1:1:1 to balcinrenone/dapagliflozin 15 mg/10 mg, 40 mg/10 mg or placebo/dapagliflozin 10 mg for 12 weeks, followed by an 8-week wash-out period to assess off-drug effects. The primary endpoint is the change in log-transformed urinary albumin-to-creatinine ratio (UACR) from baseline to Week 12. Other outcomes include pharmacokinetics, safety and tolerability.

Results: 614 patients were screened and 324 were randomized across 15 countries in Asia, Europe, North and South America. 56.2% of participants were taking SGLT2i and 87.1% renin angiotensin aldosterone system inhibitors at enrolment. The patient population are at increased risk of CKD progression by having CKD stage 3/4 and albuminuria (median UACR: 365.5 mg/g; mean eGFR: 42.2 mL/min/1.73m2). 56.5% of participants had type 2 diabetes mellitus.

Conclusions: MIRO-CKD is a fully recruited global trial enrolling a contemporary CKD population at increased risk of progression and with an increased risk of hyperkalaemia based on their reduced kidney function. The study will assess the efficacy, safety and tolerability of the combination of balcinrenone and dapagliflozin to identify an optimal dose for a future phase 3 study in patients with CKD.