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.
Brief Title
Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With 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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
(650) 624-2929
Central Contact Email
medicalaffairs@cytokinetics.com
Completion Date
Completion Date Type
Estimated
Conditions
Heart Failure
Heart Failure With Reduced Ejection Fraction
Eligibility Criteria
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
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
Inclusion Criteria
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
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
Gender
All
Gender Based
false
Keywords
CK-1827452
omecamtiv mecarbil
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
85 Years
Minimum Age
18 Years
NCT Id
NCT06736574
Org Class
Industry
Org Full Name
Cytokinetics
Org Study Id
CY 1033
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Trial to Assess Efficacy and Safety of Omecamtiv Mecarbil in Patients With Symptomatic Heart Failure With Severely Reduced Ejection Fraction (COMET-HF)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Time to the first of event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke
Outcome Time Frame
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
Secondary Ids
Secondary Id
2024-519219-32-00
Secondary Outcomes
Outcome Description
Effect of omecamtiv mecarbil compared with placebo on risk of CV death and HF event
Outcome Time Frame
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
Outcome Measure
Time to the first event of CV death or HF event
Outcome Description
Effect of omecamtiv mecarbil compared with placebo on risk of HF hospitalization
Outcome Time Frame
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
Outcome Measure
Time to the first HF hospitalization
Outcome Description
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
Outcome Time Frame
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
Outcome Measure
Time to the first event of CV death, HF event, LVAD implantation/cardiac transplantation, or stroke in a subgroup of patients with severe HF
Outcome Description
Effect of omecamtiv mecarbil compared with placebo on risk of irreversible morbidity/mortality related to HFrEF
Outcome Time Frame
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
Outcome Measure
Time to the first event of CV death, LVAD implantation/cardiac transplantation, or stroke
Outcome Description
Effect of omecamtiv mecarbil compared with placebo on risk of CV mortality
Outcome Time Frame
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
Outcome Measure
Time to CV death
Outcome Description
Effect of omecamtiv mecarbil compared with placebo on risk of stroke
Outcome Time Frame
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
Outcome Measure
Time to first event of stroke
Outcome Description
Effect of omecamtiv mecarbil compared with placebo on risk of all-cause mortality
Outcome Time Frame
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
Outcome Measure
Time to all-cause death
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
85
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Shivank Madan
Investigator Email
smadan@montefiore.org