CK-4021586 for Heart Failure

(AMBER-HFpEF Trial)

Recruiting at 23 trial locations

Overseen By Cytokinetics MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cytokinetics

Must be taking: Beta-blockers, ACE/ARB, SGLT2-inhibitors, GLP-1 agonist

Disqualifiers: Malignancy, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CK-4021586, an experimental drug for people with heart failure who have a normal ejection fraction. This means their heart pumps normally, but they still experience symptoms. Researchers aim to find the best dose of CK-4021586 by comparing different amounts of the drug over 12 weeks. Participants will be divided into groups receiving either the drug or a placebo (a substance with no therapeutic effect) for comparison. Ideal candidates for this trial have been diagnosed with heart failure, experience symptoms like shortness of breath, and maintain a stable medication regimen. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of a potentially effective treatment.

Will I have to stop taking my current medications?

The trial requires that if you are taking beta-blockers, ACE/ARB, ARNI, or SGLT2-inhibitors, you must be on a stable dose for more than 4 weeks before joining. If you're on a GLP-1 agonist, you need to be on a stable dose for more than 24 weeks with no plans to change it during the study.

Is there any evidence suggesting that CK-4021586 is likely to be safe for humans?

Research has shown that CK-4021586 has been tested for safety in humans before. An earlier study advanced it to the current stage because it showed promise in patients with heart failure with preserved ejection fraction (HFpEF), indicating it was safe enough for further testing.

Animal studies provide additional information. Tests with cats showed CK-4021586 had positive short-term effects and was tolerated without major issues. While these results don't directly apply to humans, they offer more insight into its potential safety.

The current study of CK-4021586 is in Phase 2, indicating it has demonstrated sufficient safety in earlier trials to be tested in more people. This phase typically focuses on determining the right dose, so safety remains a key focus. Overall, the treatment has shown enough safety promise to warrant further testing. ^{1 2 3 4 5}

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

Researchers are excited about CK-4021586 for heart failure because it offers a fresh approach compared to traditional treatments like ACE inhibitors, beta-blockers, and diuretics. Most current options focus on reducing symptoms and preventing disease progression. CK-4021586, however, is believed to work by enhancing the heart's performance directly, potentially improving heart function more effectively. This unique mechanism could mean better outcomes for patients, offering hope for a more robust treatment option in managing heart failure.

What evidence suggests that CK-4021586 might be an effective treatment for heart failure?

Research has shown that CK-4021586, the investigational treatment in this trial, could be promising for heart conditions. It helps the heart avoid excessive squeezing, which can be problematic in certain heart conditions. Similar drugs, such as aficamten, have benefited individuals with heart muscle issues. Early results indicate that CK-4021586 can enhance heart function and is generally well-tolerated by patients. These findings offer hope for its effectiveness in treating heart failure with preserved ejection fraction (HFpEF). ^{1 3 4 6 7}

Who Is on the Research Team?

Cytokinetics MD

Principal Investigator

Cytokinetics

Are You a Good Fit for This Trial?

Adults aged 40-85 with symptomatic heart failure (HFpEF), having a left ventricular ejection fraction (LVEF) ≥60% and classified as NYHA functional class II or III. Participants must have stable doses of certain heart medications for at least 4 weeks, a BMI under 40 kg/m2, and specific levels of NT-proBNP depending on their rhythm status.

Inclusion Criteria

Screening echocardiography with LVEF ≥ 60%

Body mass index < 40 kg/m2

I have heart failure and my symptoms are mild to moderate.

Exclusion Criteria

History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion

Other protocol-defined Inclusion/Exclusion criteria apply.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CK-4021586 or placebo daily, guided by echocardiography assessments, for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CK-4021586

Trial Overview The AMBER-HFpEF trial is testing the safety and tolerability of different doses of CK-4021586 compared to a placebo in patients with HFpEF. This Phase 2 study aims to find the right dose by randomly assigning participants to receive either the drug or placebo.

How Is the Trial Designed?

Group I: CK-4021586 - Cohort 3 Experimental Treatment 1 Intervention

Participants may receive 450 mg or 600 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.

Group II: CK-4021586 - Cohort 2 Experimental Treatment 1 Intervention

Participants may receive 300 mg or 450 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.

Group III: CK-4021586 - Cohort 1 Experimental Treatment 1 Intervention

Participants may receive 150 mg or 300 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.

Group IV: Placebo - Cohort 3 Placebo Group 1 Intervention

Participants will receive placebo daily for up to 12 weeks.

Group V: Placebo - Cohort 2 Placebo Group 1 Intervention

Participants will receive placebo daily for up to 12 weeks.

Group VI: Placebo - Cohort 1 Placebo Group 1 Intervention

Participants will receive placebo daily for up to 12 weeks.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Published Research Related to This Trial

Heart failure (HF) is classified into four types based on left ventricular ejection fraction (LVEF), and despite advancements in treatment, it still has a poor prognosis with high rates of mortality and hospitalization.

Recent large-scale clinical trials have shown that new pharmacological agents, such as sacubitril/valsartan and SGLT2 inhibitors, are effective in improving outcomes for chronic heart failure, highlighting the need for continued development of innovative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the pharmacological therapy of chronic heart failure: Evidence and guidelines. Tsutsui, H.[2022]

Chronic heart failure is increasingly common and requires standardized, evidence-based therapies, including improvements in established medications like beta blockers and mineralocorticoid receptor antagonists.

New pharmacological developments, particularly angiotensin receptor blockers and neprilysin inhibitors (ARNI), offer innovative treatment options, alongside addressing common comorbidities such as atrial fibrillation and hyperkalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic heart failure : current guideline recommendations and innovations]. Ewen, S., Mahfoud, F., Böhm, M.[2018]

Chronic heart failure is a major health issue in the U.S. and Europe, with new treatment guidelines now including ivabradine and valsartan/sacubitril, which target heart function through different mechanisms.

Ongoing clinical trials are exploring new drug candidates like non-steroidal mineralocorticoid receptor antagonists and guanylate cyclase activators, indicating a promising future for innovative therapies in heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of heart failure: From basic science to novel therapies. Lother, A., Hein, L.[2021]

Novel heart failure treatments, including SGLT2 inhibitors and ARNI, significantly reduce mortality and morbidity, even in patients with poor renal function, highlighting their efficacy across various heart failure types.

Despite concerns about worsening renal function, these therapies are essential for improving patient outcomes, and the 2021 ESC guidelines recommend their early initiation and titration to maximize benefits in heart failure with reduced ejection fraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal effects of guideline-directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology. Mullens, W., Martens, P., Testani, JM., et al.[2022]

Participation in heart failure (HF) performance improvement registries, such as ADHERE and OPTIMIZE-HF, has led to significant enhancements in the use of guideline-recommended therapies for HF, improving patient care in both hospital and outpatient settings.

These registries have not only improved adherence to quality measures but have also resulted in better clinical outcomes for patients with HF, helping to reduce disparities in care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving quality of care and outcomes for heart failure. -Role of registries-. Fonarow, GC.[2022]

Citations

1. ir.cytokinetics.com ir.cytokinetics.com/press-releases/press-release-details/2024/Cytokinetics-Announces-Data-From-Phase-1-Study-of-CK-4021586-09-09-2024/default.aspx

Cytokinetics Announces Data From Phase 1 Study of CK- ... Data from a Phase 2 clinical trial of aficamten in patients with non-obstructive HCM show that aficamten was well tolerated, improved patient ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06793371

AMBER-HFpEF: Assessment of CK-4021586 in a Multi- ... These data include demographics, such as age, sex/gender, race and ethnicity, and study-specific measures (for example, systolic blood pressure, prior ...

3. nature.com nature.com/articles/s41598-024-62840-3

Cardiac myosin inhibitor, CK-586, minimally reduces ... A single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function.

4. firstwordpharma.com firstwordpharma.com/story/5904151

Cytokinetics Highlights Progress in Cardiac Myosin ... CK-4021586 (CK-586) is a novel, selective, oral, small molecule cardiac myosin inhibitor designed to reduce the hypercontractility associated ...

5. synapse.patsnap.com synapse.patsnap.com/article/cytokinetics-releases-phase-1-study-data-on-ck-4021586

Cytokinetics Releases Phase 1 Study Data on CK-4021586 Previous studies with aficamten, another myosin inhibitor from Cytokinetics, have shown beneficial outcomes in patients with HCM, including ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06793371

AMBER-HFpEF: Assessment of CK-4021586 in a Multi- ... Also called a data safety and monitoring board, or DSMB. Early ... CK-4021586 in Adults With Symptomatic Heart Failure With Preserved Ejection Fraction.

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/568869

AMBER-HFpEF: Assessment of CK-4021586 in a Multi- ... Inclusion Criteria: Males and females ≥ 40 years and ≤ 85 years of age at screening. Diagnosed with HF with NYHA functional class II or III.