A trial to compare the efficacy and safety of aficamten (CK-3773274) compared with metoprolol succinate in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow obstruction

Prior treatment

• 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 prior to signing of informed consent) therapy with disopyramide
• History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening

Other illness

• History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening
• History of intolerance or medical contraindication to beta blocker therapy
• Resting heart rate of > 100 beats per minute (bpm) at the time of screening
• "Significant valvular heart disease a. Moderate-severe valvular aortic stenosis or fixed subaortic obstruction b. 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)

Lab values

• Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM
• Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten
• History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any time during their clinical course

Other

• Resting SBP of > 160 mmHg at the time of screening
• 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

• Males and females between 18 to 85 years of age, inclusive, at the signing of informed consent
• Body mass index < 35 kg/m2, Qualification of BMI for study eligibility is only required at the participant’s first screening visit.
• "Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography: a. Has LV hypertrophy with non-dilated LV chamber in the absence of other cardiac disease and b. 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"
• KCCQ score ≤90 at Screening Visit 2
• "Has a screening echocardiogram with the following as determined by the echocardiography core laboratory: a. Resting LVOT-G > 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND b. LVEF ≥ 60% at screening"
• Hemoglobin ≥ 10g/dL at screening
• Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks