Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (SEQUOIA-HCM)

Key Inclusion Criteria:

* Males and females between 18 and 85 years of age, inclusive, at screening.
* Body mass index \<35 kg/m2.
* Diagnosed with HCM per the following criteria:

* Has LV hypertrophy and 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 of:

* ≥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
* Has resting LVOT-G ≥30 mmHg and post-Valsalva LVOT G ≥50 mmHg during screening as determined by the echocardiography core laboratory.
* LVEF ≥60% at screening as determined by the echocardiography core laboratory.
* NYHA Functional Class II or III at screening.
* Hemoglobin ≥10g/dL at screening.
* Respiratory exchange ratio (RER) ≥1.05 and pVO2 ≤90% predicted on the screening CPET per the core laboratory.
* Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been on stable doses for \>6 weeks prior to randomization and anticipate remaining on the same medication regimen during the trial. Patients treated with disopyramide must also be concomitantly treated with a beta blocker and/or calcium channel blocker.

Key Exclusion Criteria:

* Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis).
* Significant valvular heart disease (per investigator judgment).

* Moderate-severe valvular aortic stenosis.
* Moderate-severe mitral regurgitation not due to systolic anterior motion of the mitral valve.
* 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).
* Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or has plans for either treatment during the trial period.
* Documented paroxysmal atrial fibrillation during the screening period.
* Paroxysmal or permanent atrial fibrillation is only excluded IF:

* rhythm restoring treatment (eg, direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤6 months prior to screening.
* rate control and anticoagulation have not been achieved for at least 6 months prior to screening.
* History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening.
* Has received prior treatment with CK-3773274 or mavacamten.