Aficamten for Hypertrophic Cardiomyopathy

(ACACIA-HCM Trial)

Not currently recruiting at 189 trial locations

Overseen By Cytokinetics MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cytokinetics

Must not be taking: Aficamten, Mavacamten

Disqualifiers: Valvular heart disease, Coronary artery stenosis, others

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: 72 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called aficamten for individuals with non-obstructive hypertrophic cardiomyopathy, a condition where the heart muscle thickens excessively. The goal is to assess how aficamten affects quality of life, exercise ability, and overall health compared to a placebo (a substance with no active medicine). Participants will receive either aficamten or a placebo for up to 72 weeks. Suitable candidates have experienced heart-related symptoms for some time but do not have significant heart valve issues or similar conditions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have been treated with mavacamten within 3 months prior to screening, this must be discussed with the medical monitor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found aficamten to be well tolerated over 48 weeks, with most participants experiencing no serious side effects. The research demonstrated that aficamten can relieve symptoms of obstructive hypertrophic cardiomyopathy, a condition where the heart muscle thickens excessively.

Another study showed that aficamten reduces the heart's excessive squeezing force, which can be problematic in this condition. The safety data for aficamten appears promising, indicating it is generally safe to use.

Overall, these studies suggest aficamten is a safe option, but individual experiences may vary. Always discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

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

Aficamten is unique because it specifically targets the heart muscle's contractility in hypertrophic cardiomyopathy, a condition where the heart muscle becomes abnormally thick. Unlike standard treatments like beta-blockers, calcium channel blockers, or surgical interventions, aficamten works by directly modulating the heart's myosin motor proteins, potentially reducing excessive contractions more precisely. Researchers are excited about aficamten because it offers a novel approach that may improve heart function and symptoms with a simple oral dose, providing a less invasive and potentially more effective option for patients.

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

Research has shown that aficamten, which participants in this trial may receive, may help relieve symptoms in people with hypertrophic cardiomyopathy, a condition where the heart muscle becomes too thick. In one study, 82% of participants experienced at least one level of improvement in heart function during physical activity. Another study found that aficamten significantly reduced heart blockage, leading to better heart performance and fewer symptoms. The treatment was also well tolerated, causing few side effects. Overall, early findings suggest that aficamten could improve the quality of life for people with this condition. ^{1 5 6 7 8}

Who Is on the Research Team?

Cytokinetics MD

Principal Investigator

Cytokinetics

Are You a Good Fit for This Trial?

Adults aged 18-85 with non-obstructive hypertrophic cardiomyopathy (nHCM), specifically those who are somewhat limited in physical activity but not bedridden. They must have a body mass index under 40, no recent heart surgeries or treatments with similar drugs, and be able to exercise on a treadmill or bicycle.

Inclusion Criteria

Your NT-proBNP levels meet certain requirements.

My heart condition mildly or moderately affects my daily activities.

You can join the study if you have not had a blockage in a body cavity.

Exclusion Criteria

I have a condition that causes thickening of the heart muscle, similar to nHCM.

My heart's pumping strength is below normal.

I have low oxygen levels without extra oxygen or severe lung/blood pressure issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive aficamten or placebo with dose levels guided by echocardiography assessments

72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aficamten
• Placebo

Trial Overview The trial is testing Aficamten against a placebo to see if it improves life quality, exercise ability, and health outcomes for people with nHCM. Participants will either receive the actual drug or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Aficamten Experimental Treatment 1 Intervention

Participants in this arm will receive a single daily oral dose of 5 mg, 10 mg, 15 mg, or 20 mg of aficamten with dose levels guided by echocardiography assessments, for up to 72 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants in this arm will receive placebo, for up to 72 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

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

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 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]

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]

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]

Aficamten significantly reduced left ventricular outflow tract (LVOT) gradients in patients with obstructive hypertrophic cardiomyopathy (oHCM), showing mean differences of -40 mm Hg and -43 mm Hg at rest, and -36 mm Hg and -53 mm Hg with Valsalva, compared to placebo.

The treatment was well-tolerated with no interruptions, and while there were modest reductions in ejection fraction, aficamten led to a 62% reduction in the cardiac biomarker N-terminal pro-B-type natriuretic peptide, indicating potential improvements in heart function and symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy. Maron, MS., Masri, A., Choudhury, L., et al.[2023]

Citations

1. 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.

2. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.1c01290

Discovery of Aficamten (CK-274), a Next-Generation Cardiac ... The preclinical data supported progression of aficamten into phase 1 studies where steady state was reached within 14 days of dosing and the wide therapeutic ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.038758

Safety and Efficacy of Mavacamten and Aficamten in ... In MAVA‐LTE, 5.6% of patients on mavacamten were reported to develop heart failure without a concurrent reduction in LVEF <50%, whereas 0.4% of ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213177925004202

Aficamten Treatment for Symptomatic Obstructive ... A total of 82% experienced ≥1 NYHA functional class improvement; 31% experienced a 20-point improvement in Kansas City Cardiomyopathy Questionnaire–Clinical ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2022.10.020

Phase 2 Study of Aficamten in Patients With Obstructive ... Aficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms.

6. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.035993

Dosing and Safety Profile of Aficamten in Symptomatic ... Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05186818

Study Details | NCT05186818 | Aficamten vs Placebo in ... The purpose of this study is to evaluate the efficacy and safety of aficamten (CK-3773274) versus placebo in adults with symptomatic hypertrophic cardiomyopathy ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1071916425004312

Safety and Efficacy of Aficamten in Patients With ... Efficacy and safety of aficamten in symptomatic nonobstructive hypertrophic cardiomyopathy: results from the REDWOOD-HCM trial, cohort 4. J ...