A Randomized, Double-blind, Placebo-controlled Clinical Study to Evaluate Mavacamten in Adults with Cardiomyopathy

Prior treatment

• Medical Conditions - Known infiltrative or storage disorder causing cardiac hypertrophy that mimics nHCM such as amyloidosis, Fabry disease, or Noonan syndrome with LV hypertrophy Note: Investigators should not screen participants who have comprehensive Echo features suggestive of amyloidosis, including abnormal global longitudinal strain in the setting of an appropriate clinical picture which could include low voltage on ECG and severely elevated NT-proBNP or BNP - History of unexplained syncope within 6 months prior to screening - History of sustained ventricular tachyarrhythmia (> 30 seconds) within 6 months prior to Screening - Paroxysmal or persistent (non-permanent) AF detected at the time of screening. Permanent AF is allowed if the participant is anticoagulated and the investigator considers the heart rate adequately controlled - CV diseases or treatments that in the opinion of the investigator increase the unpredictability of or change the participants' clinical course. - Acute heart failure from 4 weeks prior to screening up to randomization - Coronary artery disease requiring intervention, including myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischemia or new ischemic ECG changes), coronary artery bypass graft surgery, or other major CV surgery, stroke, or transient ischemic attack in the past 90 days - Women who are breastfeeding or pregnant. Prior/Concomitant Therapy - Any adjustments of beta-blockers, verapamil, or diltiazem within 2 weeks prior to Screening and up to the day of randomization - Concomitant use of strong inhibitors of cytochrome P450 (CYP) 2C19 Note: Use should be discontinued for a minimum of 5 elimination halflives prior to first dose of study intervention. Other Exclusion Criteria - Any other serious condition that in the opinion of the investigator could prevent participation in the study and follow-up, including active infection with COVID-19 from 4 weeks prior to screening up to randomization - Completed a study with an investigational device < 30 days prior to screening or an investigational drug < 5 half-lives prior to screening - Participants who have completed a study with mavacamten or aficamten -Enrolled in another study and receiving any investigational treatment (device or drug) other than the study intervention given in this study.

• Participants must be at least 18 years old or local age of majority at the time of signing the informed consent 2. Female participants must adhere to highly effective contraceptive methods or have documented proof that they are not of childbearing potential 3. No additional contraceptive measures are required to be used for male participants 4. Diagnosis of HCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines. 5. Peak LVOT pressure gradient < 30 mmHg at rest and < 50 mmHg with provocation (Valsalva maneuver and stress echocardiography) 6. CPET: Documented oxygen saturation at rest >90% at Screening. Able to perform an upright cardiopulmonary stress test (CPET) and has a respiratory exchange ratio (RER) ≥ 1.0 at Screening per central reading. If the RER is between 0.91 and 1.0, the participant may be enrolled if the central CPET laboratory determines that peak exercise has been achieved. Participants with subpeak performance may not be enrolled as described in the CPET Laboratory Manual. 7. New York Heart Association (NYHA) Class II or III 8. NT-proBNP≥200 pg/mL or BNP≥70 pg/mL 9. LVEF ≥60 % on screening echocardiography measured by Central Echocardiography Laboratory 10. KCCQ-23 CSS Score ≤ 85 at screening