Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
Condition: Obstructive Hypertrophic Cardiomyopathy
MeSH terms: Cardiomyopathies; Cardiomyopathy, Hypertrophic; Hypertrophy
Intervention: mavacamten; Placebo
Intervention description: mavacamten capsules; placebo oral capsule
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 251.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Symptomatic, left ventricular outflow tract gradient

Summary:

      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.
    

Eligibility criteria:

        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