a study to evaluate the efficacy, safety, and tolerability of myk-224 in participants with symptomatic obstructive hypertrophic cardiomyopathy

Conditions: Cardiomyopathy, Hypertrophic

Summary: the purpose of this study is to characterize the safety, tolerability, efficacy, pharmacokinetics (pk), and pharmacodynamics (pd) of myk-224 in participants with obstructive hypertrophic cardiomyopathy (ohcm)


Eligibility criteria:
inclusion criteria: * has adequate acoustic windows, to enable accurate ttes as determined by the echocardiography core laboratory. * men or women diagnosed with ohcm consistent with current american college of cardiology foundation/american heart association and european society of cardiology guidelines, satisfying both of the following criteria: * has unexplained left ventricular (lv) hypertrophy with nondilated ventricular chambers in the absence of other cardiac (eg, hypertension, aortic stenosis) or systemic disease and with maximal lv wall thickness ≥ 15 millimeter (mm) (or ≥ 13 mm with positive family history of hypertrophic cardiomyopathy or with a known disease-causing mutation), as determined by core laboratory interpretation. and -- has a lvot peak gradient during screening as assessed by echocardiography of ≥ 50 millimeters of mercury (mm hg) at rest, or ≥ 30 mm hg at rest and ≥ 50 mm hg with valsalva maneuver (confirmed by echocardiography core laboratory interpretation). * has resting lvef ≥ 60% at the screening visit as determined by echocardiography core laboratory. * new york heart association (nyha) functional class ii or iii symptoms at screening. * has a valid measurement of lvot post-exercise peak gradient at screening as determined by echocardiography core laboratory. exclusion criteria: * presence of any medical condition that precludes exercise stress testing. * history of syncope or sustained ventricular tachyarrhythmia within 6 months prior to screening. * known infiltrative or storage disorder causing cardiac hypertrophy that mimics hcm, such as fabry disease, amyloidosis, or noonan syndrome with left ventricular hypertrophy. * prior treatment with mavacamten or aficamten. an exception may be made in cases where myosin inhibitor use was not within 4 months of the screening visit, and with the agreement of both the investigator and the medical monitor. * has been successfully treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation \[asa\]) within 6 months prior to screening or plans to have either of these treatments during the study (note: individuals with an unsuccessful myectomy or percutaneous asa procedure performed \> 6 months prior to screening may be enrolled if study eligibility criteria for lvot gradient criteria are met). * implantable cardioverter-defibrillator (icd) placement or pulse generator change within 2 months prior to screening or planned new icd placement during the study (pulse generator changes, if needed during the study are allowed). * has a history of resuscitated sudden cardiac arrest (any time) or known history of appropriate implantable cardioverter-defibrillator (icd discharge for life-threatening ventricular arrhythmia within 6 months prior to screening. * has paroxysmal, atrial fibrillation with atrial fibrillation present per the investigator's evaluation of the participant's ecg at the time of screening. * has persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to screening and/or not adequately rate controlled within 6 months prior to screening (note: participants with persistent or permanent atrial fibrillation who are anticoagulated and adequately rate-controlled are allowed). * has qt interval with fridericia correction (qtcf) \> 500 msec when qrs interval \ 520 msec when qrs ≥ 120 msec if participant has left bundle branch block or any other 12-lead ecg abnormality considered by the investigator to pose a risk to participant safety (eg, second-degree atrioventricular block type ii). * has known moderate or severe (per investigator's judgment) aortic valve stenosis at screening. * history of lv systolic dysfunction (lvef \< 45%) at any time during their clinical course. * clinically significant pulmonary disease associated with exertional dyspnea. * has known significant unrevascularized obstructive coronary artery disease (\>70% stenosis in one or more main epicardial coronary arteries) or history of myocardial infarction note: participants with prior coronary artery bypass grafting (cabg) or percutaneous coronary interventions (pcis) are allowed if the procedure was performed at least 12 weeks prior to screening * prior treatment with cardiotoxic agents such as anthracyclines (eg, doxorubicin) or similar other protocol-defined criteria apply.

Keywords: obstructive hypertrophic cardiomyopathy myk-224 bms-986435 hcm