Aficamten for Pediatric Hypertrophic Cardiomyopathy

(CEDAR-HCM Trial)

Recruiting at 42 trial locations

Overseen By Cytokinetics MD

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

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 This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a medication called aficamten for children with obstructive hypertrophic cardiomyopathy (oHCM), a condition that hinders the heart's ability to pump blood properly. Participants will receive either aficamten or a placebo (a pill with no active medicine) for a set period, after which all participants will eventually receive aficamten. This trial suits children aged 12 to under 18 who have been diagnosed with oHCM and experience symptoms affecting their daily life. As a Phase 2, Phase 3 trial, it evaluates aficamten's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to important research.

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.

Is there any evidence suggesting that aficamten is likely to be safe for children with hypertrophic cardiomyopathy?

Research has shown that aficamten is well-tolerated in past studies. In one study, participants who took aficamten for 48 weeks experienced fewer symptoms and less heart blockage. Importantly, they tolerated it well, with no need to stop due to side effects. Another study found no major heart problems or treatment interruptions from issues like worsening heart failure, where the heart can't pump enough blood.

These findings indicate that aficamten has demonstrated a good safety profile in adults, with few serious side effects reported. While these studies focused on adults, they offer initial reassurance about the treatment's safety as researchers now study it in children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypertrophic cardiomyopathy?

Researchers are excited about aficamten for pediatric hypertrophic cardiomyopathy because it offers a novel approach compared to standard treatments like beta-blockers or calcium channel blockers. Aficamten is unique because it targets cardiac myosin directly, potentially improving heart muscle function by reducing excessive contraction, which is the hallmark of hypertrophic cardiomyopathy. Unlike conventional therapies that manage symptoms, aficamten's mechanism of action aims to address the underlying cause, providing a more targeted, potentially more effective treatment option.

What evidence suggests that aficamten might be an effective treatment for hypertrophic cardiomyopathy?

Research shows that aficamten holds promise for treating obstructive hypertrophic cardiomyopathy (oHCM). Studies have found that aficamten significantly reduces heart blockage and related symptoms. Participants in this trial may receive aficamten, which helps the heart beat less forcefully, leading to quick symptom relief. Importantly, the effects of aficamten can be quickly reversed, enhancing its safety. Overall, clinical trials have demonstrated that aficamten is effective and well tolerated over long periods. ^{1 2 3 4 6}

Who Is on the Research Team?

Cytokinetics MD

Principal Investigator

Cytokinetics

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Aficamten

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.

How Is the Trial Designed?

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, for another 52 weeks during the open-label extension period, and for an additional 144 weeks during the long-term extension period.

Group II: Placebo Placebo Group 2 Interventions

Participants in this arm will receive a single daily oral dose of placebo for 12 weeks during the double-blinded period and then will receive aficamten for 52 weeks during the open-label extension period, followed by an additional 144 weeks of aficamten during the long-term extension period.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06412666

NCT06412666 | A Study to Evaluate the Effect of Aficamten ...

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

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40540987/

48-Week Results From FOREST-HCM

Aficamten treatment over 48 weeks was well tolerated and associated with substantial and durable relief of obstruction and symptom burden.

3.

jacc.org

jacc.org/doi/10.1016/j.jacc.2024.09.003

Impact of Aficamten on Disease and Symptom Burden in ...

Treatment with aficamten, a novel cardiac myosin inhibitor, in patients with oHCM was associated with broad clinical efficacy, including rapid ...

4.

clinicaltrials.ucsf.edu

clinicaltrials.ucsf.edu/trial/NCT06412666

Aficamten in Pediatric Patients With Symptomatic ...

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

5.

ahajournals.org

ahajournals.org/doi/10.1161/JAHA.124.035993

Dosing and Safety Profile of Aficamten in Symptomatic ...

While aficamten was effective at relieving obstruction by reducing cardiac contractility, its effects are rapidly reversible, which implies that ...

6.

ir.cytokinetics.com

ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Presents-New-Data-Related-to-Aficamten-at-the-HFSA-Annual-Scientific-Meeting-2025/default.aspx

Cytokinetics Presents New Data Related to Aficamten at ...

Additional Data from MAPLE-HCM Show Aficamten Significantly Improves Measures of Maximal and Submaximal Exercise Capacity and Recovery ...