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 (MAPLE-HCM)
Obstructive Hypertrophic Cardiomyopathy (oHCM)
About this trial
This is an interventional treatment trial for Obstructive Hypertrophic Cardiomyopathy (oHCM) focused on measuring Obstructive Hypertrophic Cardiomyopathy, Aficamten, Metoprolol, oHCM, CK-3773274, CK-274, MAPLE-HCM, MAPLE, CY 6032
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: ≥ 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 NYHA class II or III 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 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 Moderate-severe valvular aortic stenosis or fixed subaortic obstruction 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
Sites / Locations
- Alaska Heart and Vascular InstituteRecruiting
- Mayo ClinicRecruiting
- Cedars-Sinai Medical Center (Smidt Heart Institute)Recruiting
- Yale New Haven HospitalRecruiting
- Northwestern UniversityRecruiting
- Massachusetts General HospitalRecruiting
- Brigham and Women's HospitalRecruiting
- Lahey Hospital & Medical CenterRecruiting
- Saint Luke's Hospital of Kansas CityRecruiting
- Morristown Medical CenterRecruiting
- Oregon Health & Science UniversityRecruiting
- Division of Heart Failure and Transplantation (Hospital of the University of Pennsylvania)Recruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Aficamten up to 20 mg plus placebo for metoprolol
Metoprolol succinate up to 200 mg plus placebo for aficamten
Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks.
Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.