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

This clinical trial will study the effects of aficamten (versus placebo) on the quality of life, exercise capacity, and clinical outcomes of patients with non-obstructive hypertrophic cardiomyopathy.

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.