Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM

Inclusion Criteria: * Between 18-85 years of age * Body mass index \< 40 kg/m2 * Diagnosed with nHCM and has a screening echocardiogram with the following: * End-diastolic left ventricular (LV) wall thickness: * ≥ 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 AND * Resting LVOT-G \< 30 mmHg AND Valsalva LVOT-G \< 50 mmHg AND * LVEF ≥ 60% * Participants with a history of intracavitary obstruction are eligible. * NYHA class II or III * Respiratory exchange ratio of ≥ 1.00 at screening by cardiopulmonary exercise testing (CPET) and predicted peak oxygen uptake (pVO2) ≤ 90% for age and sex * KCCQ-CSS score of ≤ 85 * NT-proBNP of: * NT-pro BNP ≥ 300 pg/mL or NT-proBNP ≥ 900 pg/mL if in atrial fibrillation or atrial flutter OR * For Black participants, an NT-pro BNP ≥ 225 pg/mL or NT-proBNP ≥ 675 pg/mL if in atrial fibrillation or atrial flutter Exclusion Criteria: * Significant valvular heart disease (per Investigator judgment) * Moderate or severe valvular aortic stenosis or fixed subaortic obstruction * Moderate or severe mitral regurgitation * Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics nHCM (eg, Noonan syndrome, Fabry disease, amyloidosis) * Known current unrevascularized coronary artery stenosis of ≥ 70% or documented history of myocardial infarction. * History of LV systolic dysfunction (LVEF \< 45%) or stress cardiomyopathy * Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations) * Documented room air oxygen saturation reading \< 90% at screening or history of significant chronic obstructive pulmonary disease or severe/significant pulmonary hypertension * History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 3 months prior to screening * History of resistant hypertension (persistently elevated blood pressure despite maximal doses of 3 or more classes of medications for hypertension control) * Screening diastolic blood pressure ≥ 100 mmHg * Received prior treatment with aficamten * Received treatment with mavacamten within 3 months prior to screening (must be discussed with the medical monitor prior to screening) * Undergone septal reduction therapy \< 6 months prior to screening * Is being considered for or is likely to be considered for heart transplant listing or left ventricular assist device placement during the study period * Paroxysmal or permanent atrial fibrillation is excluded only if: * rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤ 3 months prior to screening * rate control and anticoagulation have not been achieved for at least 3 months prior to screening.