Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction

Inclusion Criteria:

Adult patients who meet all the following criteria at screening may be included in the study:

• Are between ≥ 18 years and ≤ 85 years at the signing of informed consent

• Have a history of chronic HFrEF, defined as requiring treatment for HF for a minimumof 3 months prior to screening

• Are receiving oral loop diuretics on a regular schedule

• Patients without AFF on screening ECG:

• LVEF < 30% within 6 months of screening

• Elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) ≥ 1000pg/mL (BNP ≥ 300 pg/mL)

• Patients with AFF on screening ECG:

• LVEF < 25% within 6 months of screening

• Elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) ≥ 3000pg/mL (BNP ≥ 900 pg/mL)

• Not currently taking digoxin

• Meet one of the following criteria for a recent HF event:

• Are currently hospitalized with the primary reason of HF

• Had an HF event (as defined in the primary endpoint) within 12 months prior toscreening. For the purposes of a qualifying HF event, subcutaneous furosemidewill be treated as equivalent to intravenous furosemide Or

• Had outpatient escalation of oral diuretics due to worsening signs and symptomsof heart failure plus one of two additional criteria sustained for at least 1week: (1) at least 50% or 1.5-fold increase in daily loop-diuretic-equivalentdose; (2) the addition of a new diuretic class to a loop diuretic.

• Are established on regional standard-of-care HF therapies for at least 30 days priorto screening

• Systolic blood pressure ≤ 140 mmHg

Exclusion Criteria:

Any of the following criteria will exclude potential patients from the study:

• Have AFF on the screening ECG and are currently taking digoxin

• Have had any event or procedure that may have resulted in a change in ejectionfraction, including, but not limited to, acute coronary syndrome and/or any coronaryrevascularization, cardiac surgery, valve surgery, any coronary revascularization,and/or cardiac resynchronization, or cardiac contractility modulation therapy within 3 months of screening

• Are admitted to a long-term care facility or hospice

• Have a projected survival of < 12 months due to non-cardiovascular causes based onclinical judgment

• Are receiving intravenous inotropes or intravenous vasopressors ≤ 3 days prior toscreening

• Are receiving mechanical hemodynamic support or mechanical ventilation ≤ 7 daysprior to screening

• Are receiving intravenous diuretics, intravenous vasodilators, or supplementaloxygen therapy ≤ 12 hours prior to screening (except for nocturnal supplementaloxygen for sleep apnea or heart failure)

• Have an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 or receivingdialysis at screening

• Have previously had a solid organ transplant

• Are receiving treatment in another investigational device or drug study or arewithin 30 days of ending such investigational treatment at screening

• Have received omecamtiv mecarbil in a previous clinical trial

• Are pregnant or planning pregnancy during the study period, or planning tobreastfeed during treatment with IP or within 5 days after the end of treatment withIP

• Have primary infiltrative cardiomyopathy (e.g. cardiac amyloidosis) or severestenotic valvular disease