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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cytokinetics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

23 Jun 2025 → ongoing

Decision date (initial)

2025-06-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Cytokinetics, Inc.

External identifiers

EU CT number

2024-519219-32-00

ClinicalTrials.gov

NCT06736574

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the 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 objectives 7

1. 1. To evaluate the effect of omecamtiv mecarbil compared with placebo on risk of HF outcomes including left ventricular assist device implantation, cardiovascular death, HF event and stroke
2. 2. To evaluate the effect of omecamtiv mecarbil compared with placebo on HF hospitalization
3. 3. To evaluate the 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 heart failure event within the last 3 months
4. 4. To evaluate the effect of omecamtiv mecarbil compared with placebo on the risk of irreversible morbidity/mortality related to HFrEF
5. 5. To evaluate the effect of omecamtiv mecarbil compared with placebo on risk of CV mortality
6. 6. To evaluate the effect of omecamtiv mecarbil compared with placebo on risk of stroke
7. 7. To evaluate the effect of omecamtiv mecarbil compared with placebo on risk of all-cause mortality

Conditions and MedDRA coding

Heart Failure With Reduced Ejection Fraction

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board

EMA paediatric investigation plan (PIP)

EMEA-624973-PIP20-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. 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 decompensation - 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

Exclusion criteria 1

1. 1. •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 ejection fraction, including, but not limited to, acute coronary syndrome, and/or any coronary revascularization, cardiac surgery, valve surgery, 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 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 (except for nocturnal supplemental oxygen for sleep apnea or heart failure) • 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 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 •Have primary infiltrative cardiomyopathy (e.g. cardiac amyloidosis) or severe stenotic valvular disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to the first event of the following components: • CV death • HF event

Secondary endpoints 7

1. 1. Time to first HF event, CV death, LVAD implantation/cardiac transplantation or stroke
2. 2. Time to the first HF hospitalization
3. 3. Time to the first HF event, CV death, LVAD implantation/cardiac transplant, or stroke in a subgroup of patients with severe heart failure (LVEF < 30%, NYHA class 3-4, HF event within the last 3 months)
4. 4. Time to the first event of the following components: CV death, LVAD implantation/cardiac transplantation, and strok
5. 5. Time to CV death
6. 6. Time to first event of stroke
7. 7. Time to all-cause death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cytokinetics Inc.

Sponsor organisation

Cytokinetics Inc.

Address

350 Oyster Point Boulevard

City

South San Francisco

Postcode

94080-1912

Country

United States

Scientific contact point

Organisation

Cytokinetics Inc.

Contact name

Medical Director, Clinical Research, Cardiovascular

Public contact point

Organisation

Cytokinetics Inc.

Contact name

Medical Affairs

Third parties 12

Locations

6 EU/EEA countries · 77 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 66 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications