Phase 2 study for people with Heart Disease

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria:

• Age 40-84 years (both inclusive) at the time of signing the informed consent.

• Documented symptomatic heart failure (HF) diagnosed greater than or equal to (≥) 180 days prior to screening with at least weekly need for oral diuretic treatment, and New York Heart Association class II-III at screening.

• Clinically stable and on optimized doses and unchanged drug classes of guideline-directed HF therapy ≥ 45 days prior to randomisation.

• Left ventricular ejection fraction (LVEF) less than (<) 50 percent (%) as assessed by echocardiography at screening, measured by central laboratory.

• Left ventricular hypertrophy or left ventricular dilatation assessed by echocardiography at screening measured by central laboratory with any of the following:

  1. LVMi greater than (>)88 g/m^2 for female participants and >102 g/m^2 for male participants using the truncated ellipsoid method.
  2. LVMi >95 g/m^2 for female participants and >115 g/m^2 for male participants, using the linear method (cube formula).
  3. Left ventricular end-diastolic diameter indexed to body surface area (LVEDDi) >3.1 cm/m^2 for female participants and >3.0 cm/m^2 for male participants.

• Body mass index 18.5-40 kilogram per meter square (kg/m^2) (both inclusive) and body weight less than or equal to (≤) 140 kilogram (kg). Body mass index is calculated in the electronic case report form based on height and body weight at the screening visit (visit 1).

• N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥ 300 picograms per milliliter (pg/mL); NT-proBNP ≥600 pg/mL if atrial fibrillation/flutter is present at time of screening, measured by central laboratory.

Exclusion Criteria:

• Estimated Glomerular Filtration Rate (eGFR) less than (<) 30 milliliter/minute/ 1.73-meter square (mL/min/1.73 m^2) at time of screening, measured by central laboratory.
• Participants with an episode of acute kidney failure or acute kidney injury, at the discretion of the investigator,within 90 days prior to randomisation.
• Myocardial infarction, unstable angina pectoris or HF hospitalization within 30 days prior to screening.
• Participants receiving intravenous HF medications within 45 days prior to randomisation.
• Planned coronary revascularization, pacemaker/cardioverter-defibrillator/cardiac resynchronization therapy (CRT) implantation, ablation of cardiac arrythmias or valve repair/replacement at the time of randomisation.
• Stroke or transient ischemic attack within 12 months prior to randomisation.
• Participants with potential disruption of the blood-brain barrier (e.g., multiple sclerosis), in the opinion of the investigator.
• Known history of severe liver disease and/or alanine aminotransferase or aspartate aminotransferase greater than (>) 2.5x upper limit of normal at screening, measured by central laboratory.
• Known genetic (or highly suspected due to family history) cause of increased cardiac mass (including dilated cardiomyopathy, Fabry disease and likely pathogenic or pathogenic variants within hypertrophic cardiomyopathy (HCM).
• Participants with suspected or diagnosed cardiac amyloidosis or sarcoidosis.