Omecamtiv Mecarbil for Heart Failure

(COMET-HF Trial)

Recruiting at 171 trial locations

Overseen By Cytokinetics MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cytokinetics

Must be taking: Loop diuretics

Must not be taking: Digoxin

Disqualifiers: Acute coronary syndrome, Dialysis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

1800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, omecamtiv mecarbil (a cardiac myosin activator), to determine its effectiveness for people with heart failure, particularly those with a very weak heart pump (reduced ejection fraction). The study aims to assess whether the drug can reduce the likelihood of hospitalization, heart transplant, or life-threatening situations. Participants will receive either the drug or a placebo (a harmless pill with no active ingredient) and will be monitored for specific heart-related events. Suitable candidates for this trial include individuals who have managed heart failure for at least three months and experience serious symptoms, such as frequent hospital visits due to heart failure. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for heart failure.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking digoxin and have atrial fibrillation. You must also be on standard heart failure treatments for at least 30 days before joining the study.

Is there any evidence suggesting that omecamtiv mecarbil is likely to be safe for humans?

Research has shown that omecamtiv mecarbil is generally safe for people with heart failure. In studies, patients did not report major side effects from the drug. It reduced the time to the first heart failure event or death from heart-related issues, potentially lowering the risk of serious heart problems. As a Phase 3 trial, earlier trials found the treatment safe enough for testing in more people. This phase is crucial for confirming the drug's safety and effectiveness before approval for wider use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Omecamtiv Mecarbil is unique because it works by directly enhancing cardiac muscle contractility, which is different from most heart failure treatments that primarily focus on reducing blood pressure or managing fluid levels. This drug targets the heart muscle to improve its ability to pump blood more effectively, addressing the root cause of heart failure rather than just the symptoms. Researchers are excited about Omecamtiv Mecarbil because it offers a new mechanism of action that could improve outcomes for patients with heart failure, potentially leading to fewer hospitalizations and a better quality of life.

What evidence suggests that omecamtiv mecarbil might be an effective treatment for heart failure?

Studies have shown that omecamtiv mecarbil, which participants in this trial may receive, can improve heart function in patients with severe heart failure and a very low ejection fraction (the heart's ability to pump blood). Research indicates that this drug may reduce the risk of serious heart problems, such as hospitalization or death. Data from previous studies highlight its potential to enhance heart health for these patients. Additionally, findings suggest that omecamtiv mecarbil strengthens heart muscle contractions, aiding in more effective blood pumping. This treatment could offer a promising option for those facing severe heart failure. ^{1 2 5 6 7}

Who Is on the Research Team?

Cytokinetics MD

Principal Investigator

Cytokinetics

Are You a Good Fit for This Trial?

This trial is for people with chronic heart failure who have a severely reduced ejection fraction, which means their hearts are not pumping blood well. Participants should meet specific health criteria but the provided details on eligibility are incomplete.

Inclusion Criteria

* 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

* Have a left ventricular ejection fraction (LVEF) \< 30% measured within the prior 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either omecamtiv mecarbil or placebo twice daily until at least 850 participants experience a HF event or CV death

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Omecamtiv Mecarbil

Trial Overview

The study is testing Omecamtiv Mecarbil (OM), an experimental drug, to see if it can help reduce complications from heart failure like hospital stays, needing a transplant, or risk of death. Some participants will receive OM while others will get a placebo for comparison.

How Is the Trial Designed?

Group I: Omecamtiv Mecarbil Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Published Research Related to This Trial

In a study involving 20 healthy subjects, the bioavailability of omecamtiv mecarbil (OM) was assessed using two novel minitablet formulations, showing that the slow-release minitablets had similar bioavailability to the adult matrix formulation, indicating they could be effective for pediatric use.

The fast-release minitablets demonstrated even higher bioavailability compared to the adult formulation, with no serious adverse events reported, suggesting a favorable safety profile for these new formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative Bioavailability of Omecamtiv Mecarbil Pediatric Minitablet Formulations in Healthy Adult Subjects. Trivedi, A., Mackowski, M., Jafarinasabian, P., et al.[2021]

In a real-life study of 118 patients with acute myeloid leukemia (AML) in France, venetoclax combined with hypomethylating agents or low-dose cytarabine showed promising efficacy, with overall response rates of 51.9% and 41.2%, respectively.

The median progression-free survival was 4.0 months for venetoclax with hypomethylating agents and 3.4 months with low-dose cytarabine, indicating that while effective, treatment complexity necessitates harmonization of practices across treatment centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective, real-life study of venetoclax plus azacitidine or low-dose cytarabine in French patients with acute myeloid leukemia ineligible for intensive chemotherapy. Laloi, L., Billotey, NC., Dumas, PY., et al.[2023]

In a study of 35 patients with advanced blood disorders, the combination of venetoclax and hypomethylating agents resulted in a composite complete remission rate of 42.9% and a median overall survival of 9.7 months, indicating its potential efficacy for patients unfit for intensive chemotherapy.

Patients with complex karyotypes had significantly poorer outcomes, with a median overall survival of only 3.7 months, while those with SRSF2 mutations showed a higher remission rate (80%) but no significant difference in overall survival, highlighting the need for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with hypomethylating agent for the treatment of advanced myeloproliferative neoplasms and acute myeloid leukemia with extramedullary disease. Sanber, K., Ye, K., Tsai, HL., et al.[2023]

In the GALACTIC-HF trial, omecamtiv mecarbil showed consistent cardiovascular benefits for Black patients with heart failure, similar to those observed in White patients, indicating its efficacy across racial groups.

The study included 562 Black patients, representing 6.8% of total enrollment, and found no significant safety concerns, suggesting that omecamtiv mecarbil is a safe treatment option for diverse populations with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omecamtiv Mecarbil in Black Patients With Heart Failure and Reduced Ejection Fraction: Insights From GALACTIC-HF. Lanfear, DE., Njoroge, JN., Adams, KF., et al.[2023]

In the GALACTIC-HF trial involving 8232 patients, omecamtiv mecarbil significantly reduced the risk of worsening heart failure events and cardiovascular death, showing similar efficacy in both hospitalized and outpatient settings.

Hospitalized patients had a higher rate of worsening heart failure events compared to outpatients, but omecamtiv mecarbil was effective in lowering this risk regardless of whether treatment was initiated during hospitalization or as an outpatient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Omecamtiv Mecarbil in Hospitalized Patients as Compared With Outpatients With HFrEF: An Analysis of GALACTIC-HF. Docherty, KF., McMurray, JJV., Diaz, R., et al.[2023]

In a study of 33 untreated acute myeloid leukemia (AML) patients receiving off-label venetoclax/azacitidine, the complete remission rate was 63.3%, which is lower than the 84.9% rate observed in a clinical trial cohort, although the difference was not statistically significant (P = .081).

The median overall survival for off-trial patients was 381 days, significantly shorter than the 880 days for trial patients (P = .041), indicating that while off-trial use is feasible, it may lead to inferior outcomes compared to clinical trial settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia. Winters, AC., Gutman, JA., Purev, E., et al.[2020]

Omecamtiv mecarbil, an oral medication for heart failure, has a long half-life of 33 hours and a clearance rate of 11.7 L/h, indicating it can be effectively dosed without frequent administration.

The study involving 4261 heart failure patients showed that factors like body weight and kidney function have a modest effect on drug exposure, suggesting that no dose adjustments are necessary for different patient subpopulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic Properties of Omecamtiv Mecarbil in Healthy Subjects and Patients With Heart Failure With Reduced Ejection Fraction. Chen, PW., Trivedi, A., Lee, E., et al.[2022]

Omecamtiv mecarbil is safe for heart failure patients, showing no increase in death or serious adverse events compared to placebo across eight studies.

The drug may improve heart function by significantly reducing heart rate and potentially enhancing left ventricular ejection fraction and systolic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of omecamtiv mecarbil for heart failure: A systematic review and meta-analysis. Alqatati, F., Elbahnasawy, M., Bugazia, S., et al.[2022]

Omacetaxine mepesuccinate demonstrated significant efficacy in chronic myeloid leukemia (CML) patients who were resistant or intolerant to two or more tyrosine kinase inhibitors, achieving a major cytogenetic response in 20% of patients, with some responses lasting over 17 months.

The treatment was generally well-tolerated, with the most common severe side effects being hematologic issues like thrombocytopenia (67%) and neutropenia (47%), indicating that while there are risks, the benefits in terms of response rates are clinically meaningful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous omacetaxine mepesuccinate in patients with chronic-phase chronic myeloid leukemia previously treated with 2 or more tyrosine kinase inhibitors including imatinib. Cortes, JE., Nicolini, FE., Wetzler, M., et al.[2021]

In the GALACTIC-HF study involving 8232 patients, omecamtiv mecarbil significantly reduced the risk of cardiovascular death or heart failure events in patients with low systolic blood pressure (SBP ≤100 mmHg), showing a hazard ratio of 0.81, indicating a strong efficacy in this high-risk group.

Importantly, omecamtiv mecarbil did not affect SBP levels over time and was well tolerated, meaning it did not increase the risk of adverse events compared to placebo, making it a safe option for patients with heart failure and low blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of omecamtiv mecarbil in heart failure with reduced ejection fraction according to blood pressure: the GALACTIC-HF trial. Metra, M., Pagnesi, M., Claggett, BL., et al.[2023]

Citations

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jacc.org/doi/10.1016/j.jacc.2021.04.065

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Omecamtiv mecarbil significantly decreased the primary endpoint of the time-to-first heart failure event or cardiovascular death in the overall trial population ...

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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) ...