Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM

Phase 3

Completed

• Conditions: Obstructive Hypertrophic Cardiomyopathy (oHCM)
• Interventions: Drug: Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg); Drug: Placebo to match aficamten; Drug: Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg); Drug: Placebo to match metoprolol succinate

• Registration Number: NCT05767346
• Lead Sponsor: Cytokinetics

Brief Summary

The purpose of this study is to compare the efficacy and safety of aficamten (CK-3773274) compared with metoprolol succinate in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-02
• Study First Submitted QC: 2023-03-02
• Study First Posted: 2023-03-14
• Study Start: 2023-06-20
• Primary Completion: 2025-02-28
• Study Completion: 2025-03-28
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

• Participants who meet all the following criteria at screening may be included in the trial:

  • Males and females between 18 to 85 years of age, inclusive, at screening

  • Body mass index < 35 kg/m2

  • Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography -

    • Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease and

    • Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory:

      1. ≥ 15 mm in one or more myocardial segments OR
      2. ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM

  • NYHA class II or III

  • Has a KCCQ-CSS score of ≤ 90 at screening

  • Has a screening echocardiogram with the following determined by the echocardiography core laboratory:

    • Resting LVOT-G > 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND
    • LVEF ≥ 60%

  • Hemoglobin ≥ 10g/dL

  • Respiratory exchange ratio (RER) ≥ 1.05 and peak oxygen uptake (pVO2) < 100% predicted on the screening CPET per the core laboratory

  • Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks

Exclusion Criteria

• Any of the following criteria will exclude potential participants from the trial:

  • Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM

  • History of intolerance or medical contraindication to beta blocker therapy

  • Resting SBP of > 160 mmHg

  • Resting heart rate of > 100 bpm

  • Significant valvular heart disease

    1. Moderate-severe valvular aortic stenosis or fixed subaortic obstruction
    2. Mitral regurgitation not due to systolic anterior motion of the mitral valve (per Investigator judgment)

  • Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)

  • History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any time during their clinical course

  • Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)

  • Documented room air oxygen saturation reading < 90% at screening

  • Planned septal reduction treatment that cannot be deferred during the trial period

  • History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening

  • History of paroxysmal or persistent atrial fibrillation or atrial flutter. Atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed.

  • Current or recent (< 4 weeks) therapy with disopyramide

  • History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening

  • Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metoprolol succinate up to 200 mg plus placebo for aficamten	Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg)	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.
Aficamten up to 20 mg plus placebo for metoprolol	Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg)	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.
Aficamten up to 20 mg plus placebo for metoprolol	Placebo to match metoprolol succinate	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.
Metoprolol succinate up to 200 mg plus placebo for aficamten	Placebo to match aficamten	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.

Primary Outcome Measures

Name	Time	Method
Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET)	Baseline to Week 24	Effect of aficamten compared with metoprolol succinate on exercise capacity in patients with symptomatic oHCM

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class	Baseline to Week 24	Effect of aficamten compared with metoprolol succinate on NYHA Functional Classification
Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)	Baseline to Week 24	Effect of aficamten compared with metoprolol succinate on participant health status
Change in left ventricular mass index (LVMI)	Baseline to Week 24	Effect of aficamten on mass of the heart as compared with metoprolol succinate
Change in left atrial volume index (LAVI)	Baseline to Week 24	Effect of aficamten on size of the heart as compared with metoprolol succinate
Change from baseline values in NT-proBNP	Baseline to Week 24	Effect of aficamten on NT-proBNP as compared with metoprolol succinate
Change in post-Valsalva LVOT-G	Baseline to Week 24	Effect of aficamten on post-Valsalva LVOT-G as compared with metoprolol succinate

Trial Locations

Locations (71)

Alaska Heart and Vascular Institute; 🇺🇸 Anchorage, Alaska, United States

Mayo Clinic; 🇺🇸 Phoenix, Arizona, United States

UC San Diego Health - Sulpizio Cardiovascular Center; 🇺🇸 La Jolla, California, United States

Cedars-Sinai Medical Center (Smidt Heart Institute); 🇺🇸 Los Angeles, California, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

AdventHealth; 🇺🇸 Orlando, Florida, United States

Emory Clinic; 🇺🇸 Atlanta, Georgia, United States

Piedmont Fayette Hospital; 🇺🇸 Fayetteville, Georgia, United States

Northwestern University; 🇺🇸 Evanston, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

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