Kidney Week

Abstract: PUB573

A Phase 2b Dose-Finding Study to Evaluate Effects of Balcinrenone/Dapagliflozin vs. Dapagliflozin in Patients with CKD and Albuminuria

Session Information

• Publication Only

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Mark, Patrick Barry, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom

Patrick Barry Mark, MBChB, PhD

• Eriksson, Anna, Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Anna Eriksson, MD, PhD

• Guzman, Nicolas Jose, Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States

Nicolas Jose Guzman, MD

• De Sousa Amorin, Erika, Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Erika De Sousa Amorin

• Leonsson Zachrisson, Maria, Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Maria Leonsson Zachrisson, MD, PhD

• Gasparyan, Samvel B., Biometrics, Late Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Samvel B. Gasparyan, PhD

• Jiang, Yunyun, Biometrics, Late Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States

Yunyun Jiang, MS, PhD

• Heerspink, Hiddo Jan L., Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink, PhD

Background

Despite current standard of care with SGLT2i being recommended 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 selective mineralocorticoid receptor (MR) modulator, expected to maintain the cardio-renal treatment benefits of MR antagonists with a reduced risk of hyperkalaemia. The combined usage of balcinrenone and dapagliflozin is therefore expected to provide complementary and additive kidney and cardiovascular protection. MIRACLE Phase II study (NCT04595370) in heart failure (HF) and CKD suggested potential for reduced albuminuria and low risk of hyperkalaemia with balcinrenone/dapagliflozin.

Methods

This Phase IIb, international, randomized, double-blind, parallel-group trial is enrolling adult patients with CKD, albuminuria and potassium 3.5 to ≤5mmol/L (NCT06350123; Figure). Participants will be randomised 1:1:1 to three treatment arms: balcinrenone/dapagliflozin 15/10mg, balcinrenone/dapagliflozin 40/10mg and dapagliflozin 10mg 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 urinary albumin-to-creatinine ratio (UACR), compared with dapagliflozin, as well as safety and tolerability. eGFR will be monitored throughout the study, to assess any acute changes and its reversibility.

Results

The primary endpoint is the relative change in UACR from baseline to week 12. Safety and tolerability will be assessed from adverse events (including AEs of special interest; hyperkalaemia, adverse renal events and hypotension), vital signs and safety laboratory parameters throughout the study.

Conclusion

The MIRO-CKD study will assess 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

• Commercial Support – AstraZeneca