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

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:

≥ 15 mm in one or more myocardial segments OR
≥ 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

Moderate-severe valvular aortic stenosis or fixed subaortic obstruction
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