#1585 Design and baseline characteristics of MIRO-CKD: a phase IIb, randomised, double-blind clinical trial to evaluate effects of balcinrenone in combination with dapagliflozin vs. dapagliflozin in patients with CKD

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Abstract Background and Aims Despite clinical benefits of sodium glucose co-transporter-2 inhibitors (SGLT2i), recommended by current guidelines for the treatment of chronic kidney disease (CKD), there is still an unmet need for managing residual risk of disease progression. Balcinrenone is a novel mineralocorticoid receptor (MR) antagonist, which based on pre-clinical data maintained the cardio-renal benefits of MR antagonists, without increasing the risk of hyperkalaemia. The combined use of balcinrenone and dapagliflozin is expected to provide complementary and additive kidney and cardiovascular protection. The MIRO-CKD study tests the hypothesis that the combination of balcinrenone with dapagliflozin is superior to dapagliflozin alone in reducing albuminuria in patients with CKD. Method MIRO-CKD is a phase IIb, international, randomised, double-blind, parallel-group trial in adults with CKD (estimated glomerular filtration rate [eGFR] ≥25 to <60 mL/min/1.73 m2), albuminuria (urinary albumin-to-creatinine ratio [UACR] >100 to ≤5000 mg/g) and potassium ≥3.5 to ≤5 mmol/L (NCT06350123), where participants have been randomised 1:1:1 to three treatment arms: balcinrenone/dapagliflozin 15 mg/10 mg, balcinrenone/dapagliflozin 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. This study will evaluate the effect of balcinrenone/dapagliflozin on UACR (primary endpoint), compared with placebo/dapagliflozin, as well as safety and tolerability and pharmacokinetics. eGFR will be monitored throughout the study, to assess any acute changes as well as its reversibility. Results Between 1 May 2024 and 18 December 2024, 613 patients were screened and 324 were randomised across 15 countries in Asia, Europe, North and South America. When entering the study, approximately 53% of patients were taking SGLT2i, 26% angiotensin converting enzyme inhibitors (ACEi) and 57% angiotensin receptor blockers (ARB). The patient population are at increased risk of CKD progression by having CKD stage 3 or 4 and albuminuria with a median UACR of 365.5 mg/g. In addition, approximately 53% of enrolled participants had type 2 diabetes mellitus (T2DM). A significant proportion (58%) have CKD stage 3b-4 indicating an increased risk of kidney failure and hyperkalaemia. Conclusion MIRO-CKD is a fully recruited global phase IIb trial enrolling a contemporary CKD population at increased risk of disease 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 with the aim to identify an optimal dose for a future phase III study in patients with CKD. Funding AstraZeneca.

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