Efficacy and Safety Evaluation of Omecamtiv Mecarbil in Patients with Heart Failure and Severely Reduced Ejection Fraction: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-519219-32-00
- Protocol
- CY 1033
- Sponsor
- Cytokinetics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of omecamtiv mecarbil compared with placebo on the risk of heart failure (HF) outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and severely reduced ejection fraction. This is conducted in the context of guideline-directed medical therapy per local standard of care. The clinical relevance of this objective lies in its potential to improve management strategies for patients with HFrEF, a condition associated with significant morbidity and mortality.
Secondary objectives include:
- Evaluating the effect of omecamtiv mecarbil compared with placebo on the risk of HF outcomes, including left ventricular assist device implantation, cardiovascular death, and stroke.
- Assessing the impact on HF hospitalization.
- Determining the effect on the risk of HF outcomes in patients with severe HF, defined as those with New York Heart Association (NYHA) class 3-4 symptoms and a recent HF event.
- Evaluating the risk of irreversible morbidity/mortality related to HFrEF.
- Assessing the risk of cardiovascular mortality.
- Evaluating the risk of stroke.
- Determining the risk of all-cause mortality.
Participants
The clinical trial involves a total of **1280 participants** diagnosed with **Heart Failure With Reduced Ejection Fraction**. The study population includes both male and female adults aged between 18 and 85 years. Participants were selected based on their history of chronic heart failure, requiring treatment for at least three months prior to screening, and are currently receiving oral loop diuretics. The trial includes individuals with a left ventricular ejection fraction (LVEF) of less than 30% or 25% depending on the presence of atrial fibrillation/flutter, and elevated levels of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). Participants are either currently hospitalized due to heart failure or have experienced a heart failure event within the last six months. They are required to be on standard heart failure therapies for at least 30 days before screening. The study population is characterized by a systolic blood pressure of 130 mmHg or lower and a diastolic blood pressure of 90 mmHg or lower. The trial includes a vulnerable population, ensuring a comprehensive evaluation of the efficacy of omecamtiv mecarbil compared to placebo in this demographic.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **Omecamtiv Mecarbil** in patients with **heart failure with reduced ejection fraction** (HFrEF). The trial aims to assess the impact of Omecamtiv Mecarbil on the risk of heart failure outcomes in patients with severely reduced ejection fraction, in the context of guideline-directed medical therapy. The study is expected to commence recruitment on May 15, 2025, and conclude by December 31, 2027, with an estimated duration of 36 months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age, history of chronic HFrEF, and current treatment regimens. Eligible participants will be randomly assigned to receive either Omecamtiv Mecarbil or a matching placebo, administered orally in the form of film-coated tablets. The maximum daily dose is set at 100 mg, with a total treatment period not exceeding 36 months. Follow-up visits will be scheduled at regular intervals to monitor the participants' health status, adherence to the treatment protocol, and any adverse events. The primary endpoint is the time to the first event of cardiovascular death or heart failure event, with secondary endpoints including time to first heart failure hospitalization and other cardiovascular outcomes.
The end-of-study visit will mark the conclusion of the participant's involvement in the trial, during which final assessments will be conducted to evaluate the long-term effects of the treatment. Participants may be withdrawn from the study prematurely if they experience significant adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial is not classified as a low-intervention study and is conducted in accordance with ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.
Treatment
The clinical trial involves the administration of **Omecamtiv Mecarbil**, a chemically synthesized active substance, provided in the form of a **film-coated tablet**. The pharmaceutical product is manufactured by Cytokinetics Inc. and is identified by the sponsor product code CK-1827452. The medication is administered orally, with a maximum daily dose of 100 mg. The treatment period extends up to 36 weeks. The primary objective is to assess the efficacy and safety of Omecamtiv Mecarbil in patients with symptomatic heart failure with severely reduced ejection fraction. Participant compliance with the dosing schedule is monitored throughout the trial.
In addition to the experimental treatment, a **matching placebo** is utilized as a comparator in this double-blind, randomized, placebo-controlled trial. The placebo is designed to mimic the appearance of the Omecamtiv Mecarbil tablets but does not contain any active pharmaceutical ingredients. The use of a placebo allows for the evaluation of the true efficacy of Omecamtiv Mecarbil by providing a baseline for comparison against the active treatment group. The placebo is administered following the same oral route and dosing schedule as the active medication to maintain the integrity of the study design.
Efficacy
The efficacy of **Omecamtiv Mecarbil** in the clinical trial will be assessed by evaluating its impact on patients with symptomatic heart failure with severely reduced ejection fraction (HFrEF). The primary endpoint for efficacy assessment is the time to the first event of cardiovascular (CV) death or heart failure (HF) event. Secondary endpoints include time to first HF event, CV death, left ventricular assist device (LVAD) implantation or transplantation, stroke, and all-cause death. These endpoints will be measured to determine the effect of the treatment on the risk of HF outcomes.
The trial is designed as a multi-center, double-blind, randomized, placebo-controlled study. Efficacy parameters will be collected and analyzed at various timepoints throughout the study duration, which is estimated to end by December 31, 2027. The trial will involve adult patients who meet specific inclusion criteria, such as having a history of chronic HFrEF and being on guideline-directed medical therapy. The study aims to confirm the effect of Omecamtiv Mecarbil on reducing the risk of HF outcomes in this patient population.
Inclusion and Exclusion 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 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
- •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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 15 May 2025 | 120 |
 Germany | Recruiting | 15 May 2025 | 140 |
 Greece | Recruiting | 15 May 2025 | 150 |
 Italy | Recruiting | 15 May 2025 | 80 |
 Poland | Recruiting | 15 May 2025 | 150 |
 Spain | Recruiting | 15 May 2025 | 170 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Omecamtiv Mecarbil | Test | FILM COATED TABLET | ORAL USE | 100 | 36 | PRD12052946 |
Matching Placebo | Placebo | N/A | — | — | — | N/A |
Omecamtiv Mecarbil | Test | FILM COATED TABLET | ORAL USE | 100 | 36 | PRD12052945 |
Omecamtiv Mecarbil | Test | FILM COATED TABLET | ORAL USE | 100 | 36 | PRD12052947 |