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

A Phase III, Randomised, Double-blind, Study to Evaluate the Effect of Balcinrenone/Dapagliflozin Compared With Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Chronic Kidney Disease (Stage 3b and 4)

The purpose of this study is to evaluate the efficacy, safety and tolerability of balcinrenone in fixed combination with dapagliflozin, compared with dapagliflozin, in patients with CKD Stage 3b and 4 (eGFR ≥ 15 to < 45 mL/min/1.73 m2) administered orally once daily in addition to SoC.

This is a population with high unmet medical need and an increased risk of CKD progression, who are frequently excluded from interventional trials.

This is a Phase III, multicentre, randomised, double-blind, double-dummy, parallel-group, active-controlled, event-driven study in participants with CKD Stage 3b and 4.

The purpose of this study is to determine if balcinrenone/dapagliflozin, compared with dapagliflozin, administered as a capsule once daily on a background of standard of care (SoC) therapy, reduces the risk of CV death, death from kidney failure, kidney failure, sustained ≥ 50% decline from baseline in eGFR, and HF events in adults with CKD Stage 3b and 4. The study will also assess safety and tolerability of balcinrenone/dapagliflozin.

Eligible patients will randomly be assigned with a 1:1 ratio to receive once daily administration of one capsule and one tablet of one of the following treatments:

1. Balcinrenone/dapagliflozin 15 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet
2. Dapagliflozin 10 mg tablet and matching placebo for balcinrenone/dapagliflozin capsule The study will be conducted at approximately 550 sites in approximately 30 countries, globally.

Inclusion Criteria:

• Age ≥ 18 years

• Diagnosis of CKD and at least one of the following:

  1. 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).
  2. 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.

Exclusion Criteria:

• Recent (within 90 days prior to screening) or ongoing dialysis, or likely to require dialysis within 3 months following randomisation

• 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.

• HbA1c > 9% at screening

• T1DM, except:

  1. 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.
  2. 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.

• Autosomal dominant polycystic kidney disease.

• Major cardiac or valvular surgery, acute coronary syndrome (myocardial infarction or unstable angina), stroke, transient ischaemic attack within 12 weeks prior to screening.

• Severe hepatic impairment (Child-Pugh Class C).

• Adrenal insufficiency.

• 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.

• Any use of the following medications and supplements:

  1. MRAs
  2. Aldosterone analogues
  3. Aldosterone synthase inhibitors
  4. Any use of potassium binders within 2 weeks prior to screening. Use is allowed after randomisation.
  5. Strong or moderate inducers or inhibitors of CYP3A4, prohibited at least one week prior to randomisation