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

• Status: Not yet recruiting
• Trial end date: 2025-10-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cytokinetics
• Treatments: Metoprolol

Criteria

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 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

• 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