Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM)
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This is a multicenter, international, double-blind study of the administration of mavacamten in participants with symptomatic obstructive HCM (oHCM). Approximately 220 participants will be randomized to receive placebo or mavacamten.
Percentage of Participants Achieving A Clinical Response [ Time Frame: 30 weeks ]
A positive clinical response (value="YES") is defined as having an improvement in symptom severity from baseline to Week 30 as assessed by New York Heart Association (NYHA) functional classification (e.g. I, II, III, or IV) and increase in exercise capacity from baseline to Week 30 as assessed by measurement of peak oxygen consumption (pVO2) (e.g.1.5 mL/min/kg) determined by cardiopulmonary exercise testing (CPET). Or no worsening in symptom severity from baseline to Week 30 as assessed by New York Heart Association (NYHA) functional classification (e.g. I, II, III, or IV) and increase in exercise capacity from baseline to Week 30 as assessed by measurement of peak oxygen consumption (pVO2) of 3.0 mL/min/kg determined by cardiopulmonary exercise testing (CPET).
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Layout table for eligibility information
Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Key Inclusion Criteria:
Age 18 and greater, body weight ≥ 45kg
Has adequate acoustic windows to enable accurate transthoracic echocardiograms (TTEs)
Diagnosed with oHCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines and satisfy both criteria:
Has documented left ventricular ejection fraction (LVEF) ≥55%
NYHA Class II or III
Has documented oxygen saturation at rest ≥90% at Screening
Is able to perform an upright CPET and has a respiratory exchange ratio (RER) ≥1.0 at Screening per central reading
Key Exclusion Criteria:
Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy
History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to Screening
History of resuscitated sudden cardiac arrest (at any time) or known history of appropriate implantable cardioverter defibrillator (ICD) discharge for life-threatening ventricular arrhythmia within 6 months prior to Screening
Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at Screening
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
Treatment (within 14 days prior to Screening) or planned treatment during the study with disopyramide or ranolazine
Treatment (within 14 days prior to Screening) or planned treatment during the study with a combination of β-blockers and calcium channel blockers
LVOT gradient with Valsalva maneuver <30 mmHg at Screening
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
ICD placement within 2 months prior to Screening or planned ICD placement during the study
Has a history or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
Prior treatment with cardiotoxic agents such as doxorubicin or similar