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

Phase 3

Recruiting

• Conditions: Heart Failure; Heart Failure With Reduced Ejection Fraction
• Interventions: Drug: Omecamtiv Mecarbil (OM); Drug: Placebo

• Registration Number: NCT06736574
• Lead Sponsor: Cytokinetics

Brief Summary

The purpose of this study is to find out if the investigational drug called omecamtiv mecarbil can reduce the risk of the effects of heart failure, like hospitalization, transplantation, or death in patients with heart failure and severely reduced ejection fraction.

Detailed Description

This study is designed to evaluate the efficacy and safety of omecamtiv mecarbil in reducing the risk of the primary composite endpoint of cardiovascular (CV) death, first heart failure (HF) event, left ventricular assist device (LVAD) implantation, cardiac transplantation, and stroke in patients with symptomatic heart failure with severely reduced ejection fraction (HFrEF).

Eligible patients will be randomized 1:1 to investigational product (IP) - omecamtiv mecarbil or placebo. The study is event-driven and will conclude when at least 850 participants experience a HF event or CV death, whichever comes first. An interim analysis for futility and efficacy based on the primary composite endpoint is planned when approximately 570 (67%) of the planned 850 first HF events or CV deaths are observed.

Estimated duration of participation: Up to 3 years.

Study Timeline

• Study First Submitted: 2024-12-03
• Study First Submitted QC: 2024-12-13
• Study First Posted: 2024-12-16
• Study Start: 2024-12-19
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-06
• Primary Completion: 2027-09
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1800

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 minimum of 3 months prior to screening

• Are receiving oral loop diuretics

• 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

• Are currently hospitalized with the primary reason of HF, or had an HF event within 6 months prior to screening

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

• Systolic blood pressure ≤ 130 mmHg and diastolic blood pressure ≤ 90 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 acute coronary syndrome, cardiac surgery, valve surgery, any coronary revascularization, and/or cardiac resynchronization 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 on clinical judgment
• 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
• Have an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 or receiving dialysis at screening
• 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 previously received omecamtiv mecarbil
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Omecamtiv Mecarbil	Omecamtiv Mecarbil (OM)	Participants randomized to omecamtiv mecarbil will be dosed based on their omecamtiv mecarbil plasma concentration at 25, 37.5 or 50 mg twice daily until at least 850 participants experience a HF event or CV death, whichever comes first.
Placebo	Placebo	Participants randomized to placebo will receive placebo twice daily until at least 850 participants experience a HF event or CV death, whichever comes first.

Primary Outcome Measures

Name	Time	Method
Time to the first of event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke	From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years	Efficacy of omecamtiv mecarbil compared with placebo on the risk of HF outcomes in patients with symptomatic HFrEF and severely reduced ejection fraction in the setting of guideline-directed medical therapy per local standard of care.

Secondary Outcome Measures

Name	Time	Method
Time to the first event of CV death or HF event	From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years	Effect of omecamtiv mecarbil compared with placebo on risk of CV death and HF event
Time to the first HF hospitalization	From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years	Effect of omecamtiv mecarbil compared with placebo on risk of HF hospitalization
Time to the first event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke in a subgroup of patients with severe HF	From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years	Effect of omecamtiv mecarbil compared with placebo on risk of HF outcomes in patients with severe HF, defined as patients with NYHA class 3-4 symptoms and a HF event within the last 3 months
Time to the first event of CV death, LVAD implantation/cardiac transplantation, or stroke	From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years	Effect of omecamtiv mecarbil compared with placebo on risk of irreversible morbidity/mortality related to HFrEF
Time to CV death	From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years	Effect of omecamtiv mecarbil compared with placebo on risk of CV mortality
Time to first event of stroke	From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years	Effect of omecamtiv mecarbil compared with placebo on risk of stroke
Time to all-cause death	From randomization to the first event of CV death or HF event, whichever occurs first, assessed until the last patient exits the study, estimated to last about 3 years	Effect of omecamtiv mecarbil compared with placebo on risk of all-cause mortality

Trial Locations

Locations (18)

Montefiore Medical Center (Moses Campus); 🇺🇸 Bronx, New York, United States

Advanced Cardiovascular, LLC; 🇺🇸 Alexander City, Alabama, United States

San Diego Cardiac Center; 🇺🇸 San Diego, California, United States

Broward Research Center; 🇺🇸 Miami Beach, Florida, United States

CHF Heart Clinical (Subject Visits & IP Shipments); 🇺🇸 Clearwater, Florida, United States

South Florida Research Solutions, LLC; 🇺🇸 Hollywood, Florida, United States

The University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

Saint Luke's Hospital of Kansas City; 🇺🇸 Kansas City, Missouri, United States

Ocala Cardiovascular Research; 🇺🇸 Ocala, Florida, United States

Cardiovascular Research of Northwest Indiana, LLC.; 🇺🇸 Munster, Indiana, United States

Reid Physician Associates; 🇺🇸 Richmond, Indiana, United States

Advanced Heart Care, LLC; 🇺🇸 Bridgewater, New Jersey, United States

Moses H. Cone Memorial Hospital Operating Corporation d/b/a Cone Health; 🇺🇸 Greensboro, North Carolina, United States

K&R Research LLC; 🇺🇸 Marion, Ohio, United States

Capital Area Research, LLC; 🇺🇸 Camp Hill, Pennsylvania, United States

Monument Health Clinical Research, a department of Monument Health Rapid City Hospital, Inc.; 🇺🇸 Rapid City, South Dakota, United States

Tennessee Center for Clinical Trials; 🇺🇸 Tullahoma, Tennessee, United States

Medresearch Inc; 🇺🇸 El Paso, Texas, United States