A Phase 2 Open-label Pilot Study Evaluating MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
Condition: Cardiomyopathy, Hypertrophic Obstructive; Left Ventricular Outflow Tract Obstruction
MeSH terms: Cardiomyopathies; Cardiomyopathy, Hypertrophic; Ventricular Outflow Obstruction, Left; Hypertrophy
Intervention: MYK-461
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this phase 2 open-label pilot study is to evaluate the efficacy,
      pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of MYK-461 in subjects
      with symptomatic HCM and LVOT obstruction aged 18-70 years.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Diagnosed with HCM (hypertrophied and non-dilated left ventricle in absence of
             systemic or other known cause), with LV wall thickness ≥ 15 mm at time of initial
             diagnosis or ≥ 13 mm with a positive family history of HCM.

          -  Age 18-70

          -  BMI 18-37kg/m2

          -  Documented LVEF ≥ 55% at the Screening visit as determined by the investigator and the
             investigational site's echocardiography laboratory.

          -  Resting LVOT gradient ≥ 30 mg Hg and post-exercise peak LVOT gradient ≥ 50 mm Hg

          -  NYHA functional class II or higher

        Key Exclusion Criteria:

          -  History of sustained ventricular tachyarrhythmia.

          -  History of syncope with exercise within past 6 months.

          -  Active infection.

          -  Persistent atrial fibrillation or atrial fibrillation at Screening or history of
             paroxysmal atrial fibrillation with resting rate document > 100bpm within 1 year of
             screening.

          -  Has QTc Fridericia (QTcF) > 500 ms, or any other ECG abnormality considered by the
             investigator to pose a risk to subject safety (e.g. second degree atrioventricular
             block type II).

          -  Aortic stenosis or fixed subaortic obstruction.

          -  History of LV systolic dysfunction (LVEF < 45%) at any time during their clinical
             course.

          -  History of obstructive coronary artery disease.

          -  History or evidence of any other clinically significant disorder, condition, or
             disease that, in the opinion of the investigator or MyoKardia physician, would pose a
             risk to subject safety or interfere with the study evaluation, procedures, or
             completion.

          -  Part A: Ongoing therapy with beta blockers, calcium channel blockers, or disopyramide.
             Subjects on any of these medications who, in the opinion of the investigator, can
             safely be withdrawn are eligible as long as medication is discontinued at least 14
             days prior to the Screening visit.

          -  Part B: Ongoing therapy with calcium channel blockers or disopyramide. Subjects on any
             of these medications who, in the opinion of the investigator, can safely be withdrawn
             are eligible as long as medication is discontinued at least 14 days prior to the
             Screening visit.

          -  Prior treatment with cardiotoxic agents such as doxorubicin or similar, or current
             treatment with antiarrhythmic drugs that have negative inotropic activity, e.g.
             flecainide or propafenone.