A Phase 2 Study of Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM)
Condition: Non-obstructive Hypertrophic Cardiomyopathy
MeSH terms: Cardiomyopathies; Cardiomyopathy, Hypertrophic; Hypertrophy
Intervention: mavacamten; Placebo
Intervention description: MYK-461; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a multicenter, exploratory, randomized, double-blind study of the administration of
      mavacamten in 60 participants with symptomatic nHCM randomized to receive a 16-week course of
      mavacamten doses titrated to achieve 1 of 2 target drug concentrations.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Diagnosed with nHCM (hypertrophied and non-dilated left ventricle in absence of
             systemic or other known cause), with LV wall thickness ≥ 15mm at Screening or ≥ 13mm
             with a positive family history of HCM.

          -  Age 18 and greater, Body weight > 45kg

          -  Documented LVEF ≥ 55% at the Screening as determined by echo central lab

          -  LVOT gradient < 30 mmHg at rest AND during Valsalva AND post-exercise

          -  NYHA functional class II or III

          -  Elevated NT-proBNP at rest

        Key Exclusion Criteria:

          -  History of syncope, sustained ventricular tachyarrhythmia with exercise, obstructive
             coronary artery disease or myocardial infarction within the past 6 months

          -  History of resuscitated sudden cardiac arrest at any time or known appropriate
             implantable cardioverter defibrillator (ICD) discharge within 6 months prior to
             Screening

          -  Current treatment with disopyramide or ranolazine (within 14 days prior to Screening)

          -  Current or planned treatment during the study with a combination of beta-blockers and
             calcium channel blockers

          -  Has been treated with invasive septal reduction (surgical myectomy or percutaneous
             alcohol septal ablation [ASA]) within 6 months prior to Screening

          -  History of resting or post-exercise LVOT >30 mmHg unless subsequently treated by
             septal reduction

          -  Has QTc Fridericia (QTcF) >480 ms or any other ECG abnormality considered by the
             investigator to pose a risk to participant safety (eg, second-degree atrioventricular
             block type II)

          -  Has persistent or permanent atrial fibrillation not on anticoagulation for at least 4
             weeks prior to Screening and/or not adequately rate-controlled within 1 year of
             Screening

          -  History of clinically significant malignant disease within 10 years such as
             non-metastatic cutaneous squamous cell or basal cell carcinoma

          -  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.