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

Prior treatment

• Have AFF on the screening ECG and are currently taking digoxin
• Are receiving intravenous inotropes or intravenous vasopressors ≤ 3 days prior to screening
• Are receiving mechanical hemodynamic support or mechanical ventilation ≤ 7 days prior to screening
• Are receiving intravenous diuretics, intravenous vasodilators, or supplemental oxygen therapy ≤ 12 hours prior to screening (except for nocturnal supplemental oxygen for sleep apnea or heart failure)
• Have previously had a solid organ transplant
• Are receiving treatment in another investigational device or drug study or are within 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 to breastfeed during treatment with IP or within 5 days after the end of treatment with IP

Other illness

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

Lab values

• Have had any event or procedure that may have resulted in a change in ejection fraction, including, but not limited to, acute coronary syndrome and/or any coronary revascularization, cardiac surgery, valve surgery, any coronary revascularization, and/or cardiac resynchronization, or cardiac contractility modulation therapy within 3 months of screening
• Have an estimated glomerular filtration rate (eGFR) \< 20 mL/min/1.73m2 or receiving dialysis at screening

Other

• Any of the following criteria will exclude potential patients from the study:
• Are admitted to a long-term care facility or hospice
• Have a projected survival of \< 12 months due to non-cardiovascular causes based on clinical judgment

• 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 minimum of 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) ≥ 1000 pg/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) ≥ 3000 pg/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 to screening. For the purposes of a qualifying HF event, subcutaneous furosemide will be treated as equivalent to intravenous furosemide Or
  • Had outpatient escalation of oral diuretics due to worsening signs and symptoms of heart failure plus one of two additional criteria sustained for at least 1 week: (1) at least 50% or 1.5-fold increase in daily loop-diuretic-equivalent dose; (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 prior to screening
• Systolic blood pressure ≤ 140 mmHg