Aficamten for Pediatric Hypertrophic Cardiomyopathy

(CEDAR-HCM Trial)

Recruiting at 27 trial locations

Overseen By Cytokinetics MD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Cytokinetics

Must be taking: Beta blockers, Verapamil

Must not be taking: Anthracyclines, Monoclonal antibodies

Disqualifiers: Valvular heart disease, Atrial fibrillation, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy, safety and PK of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

Will I have to stop taking my current medications?

The trial requires that participants on beta blockers, verapamil, diltiazem, or disopyramide have been on stable doses for more than 4 weeks before joining. It doesn't specify if you need to stop other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Aficamten for pediatric hypertrophic cardiomyopathy?

Aficamten has shown promise in reducing heart muscle overactivity and improving heart function in adults with hypertrophic cardiomyopathy, a condition where the heart muscle becomes too thick. In studies with cats, Aficamten helped improve heart function without serious side effects, suggesting it might be effective for similar heart conditions in humans. ^{1 2 3 4 5}

Is Aficamten safe for humans?

Aficamten has been shown to be safe and well-tolerated in healthy adults, with mild side effects reported in some participants. No serious adverse effects were observed in clinical trials, and it has a favorable safety profile compared to other treatments for hypertrophic cardiomyopathy. ^{1 2 3 4 5}

How is the drug Aficamten unique for treating pediatric hypertrophic cardiomyopathy?

Aficamten is unique because it is a novel cardiac myosin inhibitor that directly targets the heart muscle's contractility, reducing hypercontractility and improving heart function, unlike traditional treatments that mainly manage symptoms. It has a shorter half-life and fewer drug interactions compared to similar drugs, making it potentially more convenient and safer for long-term use. ^{1 2 3 4 5}

Research Team

Cytokinetics MD

Principal Investigator

Cytokinetics

Eligibility Criteria

This trial is for young people aged 12 to under 18 with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). They must have a certain level of heart function and obstruction, be in NYHA Class II or higher, and on stable doses of specific heart medications. Genetic testing should confirm oHCM or assume it if no other conditions are present. Participants need to weigh at least 35 kg after the initial cohort.

Inclusion Criteria

Completed Period 1. If unable to complete Period 1 due to circumstances not related to compliance or safety, the Medical Monitor may review and determine eligibility

LVEF ≥ 55% after washout

My heart condition limits my physical activity.

Exclusion Criteria

I don't have any other serious health issues that could affect my safety in the trial.

I have had or will have an ICD implant within 6 weeks of screening or during the trial.

History of congenital heart disease other than oHCM

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Randomized, double-blind, placebo-controlled treatment period to assess efficacy, safety, and tolerability of aficamten

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Open-label extension trial to assess long-term safety, efficacy, and tolerability of aficamten

52 weeks

Monthly visits (in-person)

Treatment Details

Interventions

• Aficamten (Myosin Inhibitor)

Trial Overview The study tests Aficamten's effectiveness, safety, and pharmacokinetics (how the drug moves through the body) in pediatric patients with oHCM. It compares Aficamten against a placebo – an inactive substance designed to test if the real drug works.

Participant Groups

Group I: Aficamten Experimental Treatment 1 Intervention

Participants in this arm will receive a single daily oral dose of aficamten with dose levels (5 mg to 20 mg) guided by echocardiography assessments, for 12 weeks during the double-blinded period, and then for another 52 weeks during the open-label extension period.

Group II: Placebo Placebo Group 2 Interventions

Participants in this arm will receive placebo for 12 weeks during the double-blinded period, and then will receive aficamten for 52 weeks during the open-label extension period.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Findings from Research

Aficamten was found to be safe and well-tolerated in a phase 1 study involving 28 healthy Chinese adults, with no serious adverse events reported and only mild treatment-emergent adverse events occurring in 50% of participants.

The pharmacokinetics of aficamten were dose-proportional and similar to those observed in Western populations, supporting its potential for further clinical trials in patients with obstructive hypertrophic cardiomyopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study. Zhao, X., Liu, H., Tian, W., et al.[2023]

Aficamten (CK-274) is a novel cardiac myosin inhibitor designed to treat hypercontractility in genetic hypertrophic cardiomyopathies, showing a predicted human half-life suitable for once-daily dosing and achieving steady state within two weeks.

In a phase I clinical trial, aficamten confirmed its predicted pharmacokinetic properties, indicating a wide therapeutic window and minimal interaction with cytochrome P450 enzymes, which suggests a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. Chuang, C., Collibee, S., Ashcraft, L., et al.[2021]

Mavacamten has been approved by the FDA as a novel treatment for symptomatic obstructive hypertrophic cardiomyopathy (HCM), showing improved clinical outcomes by targeting cardiac contractility at the sarcomere level.

Aficamten, another cardiac myosin inhibitor currently in phase III clinical trials, represents a promising new therapy for HCM, indicating a shift in management strategies from traditional negative inotropic agents to more targeted treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aficamten-A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy. Patel, J., Wang, A., Naidu, SS., et al.[2023]

A single oral dose of the myosin inhibitor aficamten (2 mg/kg) in five cats with hypertrophic cardiomyopathy (HCM) led to significant changes in cardiac function, including reduced left ventricular fractional shortening and improved left ventricular dimensions without major side effects.

The results suggest that while aficamten can effectively alter cardiac function in HCM, a lower dose may be more optimal, indicating the need for further studies to refine dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a single dose of Aficamten (CK-274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model. Sharpe, AN., Oldach, MS., Kaplan, JL., et al.[2023]

Aficamten is a new cardiac myosin inhibitor that effectively lowers left ventricular outflow tract (LVOT) gradients and improves heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), showing significant results within 2 weeks and sustained effects for up to 48 weeks based on the REDWOOD-HCM study.

Compared to traditional treatments like beta-blockers and calcium channel blockers, aficamten directly targets the underlying disease mechanism by reducing hypercontractility and improving diastolic function, while also having a shorter half-life and fewer drug interactions, making it a safer and more convenient option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy. Sebastian, SA., Padda, I., Lehr, EJ., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study. [2023]

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

Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. [2021]

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

Aficamten-A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a single dose of Aficamten (CK-274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy. [2023]