Long-term Safety of Aficamten for Hypertrophic Cardiomyopathy

(FOREST-HCM Trial)

Recruiting at 91 trial locations

Overseen By Cytokinetics, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Cytokinetics

Must not be taking: Mavacamten

Disqualifiers: Atrial fibrillation, Septal reduction, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

900 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken mavacamten within 56 days before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug aficamten for hypertrophic cardiomyopathy?

Aficamten has been shown to safely reduce heart muscle obstruction and improve heart failure symptoms in patients with hypertrophic cardiomyopathy, with benefits observed as early as two weeks and sustained up to 48 weeks. It works by reducing excessive heart muscle contraction and improving heart relaxation, making it a promising option compared to other treatments. ^{1 2 3 4 5}

Is aficamten safe for humans?

Aficamten has been shown to be safe and well-tolerated in both patients with hypertrophic cardiomyopathy and healthy participants, with no serious side effects reported in studies. In a study with healthy Chinese adults, mild side effects were noted, but no serious adverse events occurred. ^{1 2 3 4 5}

How is the drug aficamten different from other treatments for hypertrophic cardiomyopathy?

Aficamten is unique because it is a cardiac myosin inhibitor that directly targets the heart's muscle fibers to reduce excessive contraction, unlike traditional treatments that mainly manage symptoms. It has a shorter half-life and fewer drug interactions compared to similar drugs, making it a potentially safer and more convenient option for patients. ^{1 2 3 5 6}

What is the purpose of this trial?

This trial is focused on collecting data about the safety and tolerability of a new medication called aficamten. The study involves people who are using this medication to see if it remains safe and well-tolerated over an extended period.

Research Team

Cytokinetics, MD

Principal Investigator

Cytokinetics

Eligibility Criteria

This trial is for individuals who have completed a previous Cytokinetics study with CK-3773274 and have a left ventricular ejection fraction (LVEF) of 55% or higher. It's not open to those who've had certain heart treatments, recent atrial fibrillation, or an investigational drug/device within the last month.

Inclusion Criteria

You have already taken part in a Cytokinetics study involving CK-3773274.

Your heart function is good, with a measurement of at least 55% at the screening visit.

Exclusion Criteria

I received a necessary shock from my defibrillator within the last 30 days.

I've had heart surgery or a procedure to reduce heart muscle thickness after my last CK-3773274 trial.

I recently developed a type of irregular heartbeat and started treatment for it less than 30 days ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a daily dose of aficamten, titrated to their maximum tolerated dose

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Open-label extension

Participants continue to receive aficamten to collect long-term safety and tolerability data

Long-term

Treatment Details

Interventions

• CK-3773274

Trial Overview The trial is focused on gathering long-term safety data for Aficamten (CK-3773274), which will be administered in doses ranging from 5 to 20 mg. This is an open-label study where all participants receive the drug.

Participant Groups

Group I: Aficamten up to 20 mg Experimental Treatment 1 Intervention

Patients in this arm take daily dose of aficamten. Each patient will start at the lowest prespecified dose and titrate up to their maximum tolerated dose.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Findings from Research

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]

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]

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]

The SEQUOIA-HCM trial, involving 282 participants, is evaluating the safety and efficacy of aficamten compared to placebo in patients with obstructive hypertrophic cardiomyopathy (oHCM) over a 24-week period, aiming to improve functional capacity and reduce symptoms.

Despite advancements in managing oHCM that have lowered hospitalization and mortality rates, patients still experience significant quality of life issues, highlighting the need for effective new therapies like aficamten.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design. Coats, CJ., Maron, MS., Abraham, TP., 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]

References

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

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

2. 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]

3. 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]

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

Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design. [2023]

5. 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]

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

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