This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-861 administered once daily for 12 weeks in subjects with heart failure with reduced ejection fraction (HFrEF) who are on a stable, guideline-directed medical therapy for heart failure.

Inclusion Criteria:

• Has a clinical diagnosis of symptomatic heart failure (HF) ≥90 days prior to the Screening Visit;
• Is in New York Heart Association (NYHA) functional class II or III at the Screening Visit;
• Is on stable, guideline-directed therapy for HF, consistent with American Heart Association (AHA), American College of Cardiology (ACC), Heart Failure Society of America (HFSA) or European Society of Cardiology (ESC) guidelines for ≥4 weeks prior to the Screening Visit (with at least half of maximal labeled dose of renin-angiotensin-aldosterone system (RAAS) inhibitors and β-blockers, if tolerated);
• Has left ventricular ejection fraction (LVEF) ≤35% at the Screening Visit;
• Has a serum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) level ≥600 pg/mL (or ≥900 pg/mL if the subject has atrial fibrillation or atrial flutter) at the Screening Visit.

Exclusion Criteria:

• Has a confirmed acute myocardial infarction (MI) (i.e., Type 1) or unstable angina within 90 days prior to the Screening Visit;
• Has a history of coronary revascularization (percutaneous coronary intervention [PCI] and/or coronary artery bypass graft [CABG]) or other cardiovascular surgery within 90 days prior to the Screening Visit or planned cardiovascular surgery during the study through the Follow-up Visit);
• Has started cardiac resynchronization therapy (CRT) within 90 days prior to the Screening Visit or has planned CRT during the study through the Follow-up Visit;
• Has clinically significant congenital heart disease, active myocarditis or constrictive pericarditis;
• Has current acute decompensated HF requiring additional treatment with diuretics, vasodilators and/or inotropic medications at the Screening Visit;
• Has clinically significant chronic renal insufficiency (i.e., estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation) at the Screening Visit.