Aficamten vs Metoprolol for Hypertrophic Cardiomyopathy

(MAPLE-HCM Trial)

Recruiting at 70 trial locations

Overseen By Cytokinetics MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cytokinetics

Must not be taking: Disopyramide, Beta blockers

Disqualifiers: Hypertension, Atrial fibrillation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 24 weeks

175 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares a new drug, aficamten, with a common heart medication, metoprolol succinate, in adults with a specific heart condition that causes symptoms and blood flow blockage. Aficamten helps the heart muscle relax, while metoprolol succinate slows and eases the heart's pumping. Metoprolol has been widely used since 1975.

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 have a medical need for beta blockers or calcium-channel blockers that you can't stop. If you've taken mavacamten, you must stop it for at least 8 weeks before joining.

What data supports the effectiveness of the drug Metoprolol succinate for treating heart conditions?

Metoprolol succinate is effective in managing chronic heart failure, as it helps reduce the risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (a measure of how well the heart pumps blood). ^{1 2 3 4 5}

Is Metoprolol succinate safe for humans?

Metoprolol succinate is generally considered safe for humans and is commonly used to treat heart failure, with studies showing it has similar effects to carvedilol in reducing mortality in heart failure patients. ^{1 4 5 6 7}

How does the drug Aficamten differ from Metoprolol succinate for treating hypertrophic cardiomyopathy?

Aficamten is a novel drug specifically designed to target the underlying cause of hypertrophic cardiomyopathy by reducing excessive heart muscle contraction, whereas Metoprolol succinate is a beta-blocker that primarily manages symptoms by slowing the heart rate and reducing blood pressure. ^{1 4 7 8 9}

Research Team

Scientific Leadership

Principal Investigator

Cytokinetics

Eligibility Criteria

Adults aged 18-85 with symptomatic hypertrophic cardiomyopathy and obstruction in the heart's left ventricle can join. They should have a BMI under 35, be class II or III for heart symptoms, and meet specific heart imaging criteria. Exclusions include high blood pressure at rest, certain other heart conditions, intolerance to beta blockers, recent severe arrhythmias or fainting episodes.

Inclusion Criteria

You need to have a specific type of heart test that shows certain results.

My heart condition was confirmed by a heart scan or ultrasound.

My heart condition mildly or moderately affects my daily activities.

Exclusion Criteria

I am scheduled for a heart procedure that can't be postponed.

I have a history of irregular heartbeats.

I have taken disopyramide in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either aficamten or metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Aficamten (CK-3773274)
• Metoprolol succinate

Trial Overview The trial is testing Aficamten against Metoprolol Succinate to see which is better for adults with obstructive hypertrophic cardiomyopathy. Participants will receive varying doses of either drug or matching placebos to compare effectiveness and safety.

Participant Groups

Group I: Aficamten up to 20 mg plus placebo for metoprolol Experimental Treatment 2 Interventions

Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks.

Group II: Metoprolol succinate up to 200 mg plus placebo for aficamten Active Control 2 Interventions

Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

In a meta-analysis of 30,943 patients treated with carvedilol and 69,925 patients treated with metoprolol, carvedilol was found to reduce all-cause mortality compared to metoprolol tartrate, suggesting a potential advantage for carvedilol in this specific comparison.

However, when comparing carvedilol to metoprolol succinate, there were no significant differences in all-cause mortality or hospitalizations, indicating that both medications may be equally effective for patients with heart failure with reduced ejection fraction (HFrEF).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of the effects of carvedilol versus metoprolol on all-cause mortality and hospitalizations in patients with heart failure. Briasoulis, A., Palla, M., Afonso, L.[2018]

In a study of 974 patients with heart failure and reduced left ventricular function, atenolol showed a lower unadjusted mortality rate (3.2%) compared to metoprolol tartrate (7.5%) and was comparable to carvedilol (4.2%).

After adjusting for patient characteristics, atenolol was associated with a significantly lower risk of death compared to metoprolol tartrate, suggesting it may be an effective treatment option for heart failure, warranting further randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival among patients with left ventricular systolic dysfunction treated with atenolol. Kapoor, JR., Heidenreich, PA.[2016]

Carvedilol, unlike metoprolol, antagonizes multiple adrenoreceptors involved in heart failure and also reduces oxidative stress, suggesting it may offer superior benefits for patients with heart failure.

Despite the potential advantages of carvedilol, the actual use of beta-blockers like carvedilol and metoprolol in heart failure patients remains low, partly due to a lack of clinical trials directly comparing their efficacy at optimal doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical differences among beta-adrenoreceptor antagonists in myocardial failure: debating the MERIT of COMET. McBride, BF., White, CM.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Carvedilol or sustained-release metoprolol for congestive heart failure: a comparative effectiveness analysis. [2018]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Effect of metoprolol CR/XL on remodeling of the heart and cardiac rhythm disturbances after myocardial infarction in patients with chronic heart failure]. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Extended-release metoprolol succinate in chronic heart failure. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Meta-analysis of the effects of carvedilol versus metoprolol on all-cause mortality and hospitalizations in patients with heart failure. [2018]

5. Georgia (Republic) pubmed.ncbi.nlm.nih.gov

METOPROLOL SUCCINATE: GENETIC ASPECTS OF INDIVIDUAL SENSITIVITY AND EFFICACY IN PATIENTS WITH OBESITY AND CHRONIC HEART FAILURE. [2019]

6. France pubmed.ncbi.nlm.nih.gov

[Clinical symptoms of mitral valve prolapse. Treatment with metoprolol (author's transl)]. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Survival among patients with left ventricular systolic dysfunction treated with atenolol. [2016]

8. England pubmed.ncbi.nlm.nih.gov

Critical differences among beta-adrenoreceptor antagonists in myocardial failure: debating the MERIT of COMET. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Effect of carvedilol vs metoprolol succinate on mortality in heart failure with reduced ejection fraction. [2019]