A Phase III Study to Evaluate the Effect of Balcinrenone/Dapagliflozin in Patients With CKD Stage 3b and 4 (BalanceD-CKD)

Prior treatment

• Recent (within 90 days prior to screening) or ongoing dialysis, or likely to require dialysis within 3 months following randomisation
• T1DM, except:
  • For US only: patients with T1DM treated with SGLT2i for at least 4 months prior to screening, without DKA during that period, and who have experience with ketone monitoring are eligible.
  • For Japan only: patients with T1DM treated with dapagliflozin 10 mg for at least 4 months prior to Screening, without DKA during the period of dapagliflozin treatment are eligible for inclusion.
• Major cardiac or valvular surgery, acute coronary syndrome (myocardial infarction or unstable angina), stroke, transient ischaemic attack within 12 weeks prior to screening.
• Clinically significant acute kidney injury within 12 weeks prior to the screening.
• New York Heart Association functional HF class IV at screening, or hospitalisation for heart failure within 4 weeks prior to screening.
• Any clinical condition requiring systemic immunosuppression therapy other than maintenance therapy (stable for at least 3 months) prior to screening.
• Solid organ or bone marrow transplant or a plan for transplant within 6 months following randomisation.

Other illness

• Autosomal dominant polycystic kidney disease.
• Severe hepatic impairment (Child-Pugh Class C).
• Adrenal insufficiency.

Lab values

• HbA1c \> 9% at screening
• Any use of the following medications and supplements:
  • MRAs
  • Aldosterone analogues
  • Aldosterone synthase inhibitors
  • Any use of potassium binders within 2 weeks prior to screening. Use is allowed after randomisation.
  • Strong or moderate inducers or inhibitors of CYP3A4, prohibited at least one week prior to randomisation

Other

• UACR ≥ 5000 mg/g or UPCR ≥ 7000 mg/g at screening.
• SBP \> 180 mmHg or DBP \> 110 mmHg at screening.
• SBP \< 90 mmHg at screening.

• Age ≥ 18 years
• Diagnosis of CKD and at least one of the following:
  • eGFR ≥ 15 to \< 45 mL/min/1.73 m2 AND: UACR ≥ 30 mg/g (central laboratory) or UACR ≥ 100 mg/g (local laboratory ) or UPCR ≥ 200 mg/g (local laboratory).
  • eGFR ≥ 15 to \< 30 mL/min/1.73 m2 and UACR \< 30 mg/g (local or central laboratory UACR value).
• Serum/plasma K+ ≤ 5.0 mmol/L
• Maximum tolerated dose of an ACEi or an ARB, unless contraindicated or not tolerated. The dose should be stable for at least 4 weeks before screening.