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

Cytokinetics

Status and phase

Enrolling

Phase 3

Conditions

Heart Failure With Reduced Ejection Fraction

Heart Failure

Treatments

Drug: Placebo

Drug: Omecamtiv Mecarbil (OM)

Study type

Interventional

Funder types

Industry

Identifiers

NCT06736574

2024-519219-32-00 (EU Trial (CTIS) Number)

CY 1033

Details and patient eligibility

About

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.

Full 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.

Enrollment

1,800 estimated patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

1,800 participants in 2 patient groups, including a placebo group

Omecamtiv Mecarbil

Experimental group

Description:

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.

Treatment:

Drug: Omecamtiv Mecarbil (OM)

Placebo

Placebo Comparator group

Description:

Participants randomized to placebo will receive placebo twice daily until at least 850 participants experience a HF event or CV death, whichever comes first.

Treatment:

Drug: Placebo