Phase III study to evaluate the effect of balcinrenone/dapagliflozin in patients with heart failure

This is a Phase III, international, multi-centre, randomised, double-blind, parallel-group, double-dummy, active-controlled, event-driven study in patients with chronic HF and impaired kidney function who had a recent HF event. The aim is to evaluate the effect of balcinrenone/dapagliflozin vs dapagliflozin, given once daily on top of other classes of SoC, on CV death and HF events.

The purpose of this study is to investigate the effect of balcinrenone/dapagliflozin compared with dapagliflozin, on the risk of CV death, HF event with and without hospitalisation, in patients with chronic HF, impaired kidney function, and who have had a recent HF event.

Eligible patients will randomly be assigned with a 1:1:1 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. Balcinrenone/dapagliflozin 40 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet

3. Dapagliflozin 10 mg tablet and matching placebo for balcinrenone/dapagliflozin capsule

The study is event driven, and the average study duration for a participant is estimated to be 22 months including screening period, 20 months blinded treatment period and a one-month follow-up period on open-label dapagliflozin.

The study will be conducted at approximately 700 sites in approximately 40 countries globally.

Inclusion Criteria:

• Age ≥ 18 years

• Documented diagnosis of symptomatic HF (NYHA functional class II-IV)

• Having had a recent HF event within 6 months (hospitalization or urgent visit)

• Have a LVEF value from an assessment within the last 12 months

• Managed with SoC therapy for HF and renal impairment according to local guidelines

• NT-proBNP must be >300 pg/mL (>600 pg/mL if concomitant atrial fibrillation or atrial flutter)

• Not taking an MRA

• An eGFR ≥ 20 to < 60 mL/min/1.73 m2

• Serum/plasma potassium ≤ 5.0 mmol/L

Exclusion Criteria:

• Acute coronary syndrome (unstable angina or myocardial infarction), stroke or transient ischaemic attack within the previous 3 months prior to enrolment or during the screening period

• Major cardiac surgery, coronary revascularisation or valvular repair or replacement, or implantation of a Cardiac resynchronisation therapy device within 3 months prior to enrolment or during the screening period, or planned to undergo any of these operations

• History of hypertrophic obstructive cardiomyopathy

• Complex congenital heart disease or severe uncorrected primary valvular disease

• Symptomatic bradycardia or second* or third-degree heart block without a pacemaker

• Systolic BP < 90 mmHg, or symptomatic hypotension within the past 24 hours

• Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD or exacerbation of COPD requiring invasive mechanical ventilation assistance within 12 months prior to enrolment

• Type 1 diabetes mellitus

• Kidney replacement therapy in the past 4 weeks, currently requiring kidney replacement or imminent plan to start kidney replacement therapy

• Acute or chronic liver disease with severe impairment of liver function, eg, ascites, oesophageal varices, coagulopathy, and encephalopathy

• Suspected or confirmed COVID-19 infection within the last 4 weeks or hospitalisation for COVID-19 within the last 12 weeks

• Treatment with strong or moderate CYP3A4 inhibitor or inducer