phase 3 trial to evaluate the efficacy and safety of aficamten compared to metoprolol succinate in adults with symptomatic ohcm

Conditions: Obstructive Hypertrophic Cardiomyopathy (oHCM)

Summary: the purpose of this study is to compare the efficacy and safety of aficamten (ck-3773274) compared with metoprolol succinate in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction


Eligibility criteria:
inclusion criteria: * participants who meet all the following criteria at screening may be included in the trial: * males and females between 18 to 85 years of age, inclusive, at screening * body mass index \< 35 kg/m2 * diagnosed with ohcm per the following criteria by cardiac magnetic resonance imaging (cmr) or echocardiography - * has left ventricular (lv) hypertrophy with 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: 1. ≥ 15 mm in one or more myocardial segments or 2. ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of hcm * nyha class ii or iii * has a kccq-css score of ≤ 90 at screening * has a screening echocardiogram with the following determined by the echocardiography core laboratory: * resting lvot-g \> 30 mm hg and/or post-valsalva lvot-g ≥ 50 mmhg at screening and * lvef ≥ 60% * hemoglobin ≥ 10g/dl * respiratory exchange ratio (rer) ≥ 1.05 and peak oxygen uptake (pvo2) \< 100% predicted on the screening cpet per the core laboratory * patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks exclusion criteria: * any of the following criteria will exclude potential participants from the trial: * medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than ohcm * history of intolerance or medical contraindication to beta blocker therapy * resting sbp of \> 160 mmhg * resting heart rate of \> 100 bpm * significant valvular heart disease 1. moderate-severe valvular aortic stenosis or fixed subaortic obstruction 2. mitral regurgitation not due to systolic anterior motion of the mitral valve (per investigator judgment) * known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics ohcm (eg, noonan syndrome, fabry disease, amyloidosis) * 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) * documented room air oxygen saturation reading \< 90% at screening * planned septal reduction treatment that cannot be deferred during the trial period * history of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening * history of paroxysmal or persistent atrial fibrillation or atrial flutter. atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed. * current or recent (\< 4 weeks) therapy with disopyramide * history of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening * has received prior treatment with aficamten or previously intolerant (reduced lvef requiring permanent drug discontinuation) to mavacamten

Keywords: obstructive hypertrophic cardiomyopathy aficamten metoprolol ohcm ck-3773274 ck-274 maple-hcm maple cy 6032