A Phase 2 Study of Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM)

Study Overview
=================
Brief 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.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Concentration-guided, Exploratory Study of Mavacameten in Patients With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM) and Preserved Left Ventricular Ejection Fraction

Conditions
-----------------
Non-obstructive Hypertrophic Cardiomyopathy

Intervention / Treatment
-----------------
* Drug: mavacamten
* Drug: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Active Treatment for participants with base target trough concentration | Drug: mavacamten<br>* MYK-461<br>* Other names: MYK-461;|
| Experimental: Group 2<br>Active Treatment for participants with higher target trough concentration | Drug: mavacamten<br>* MYK-461<br>* Other names: MYK-461;|
| Placebo Comparator: Placebo<br>Placebo Group | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAE) | This is the percentage of participants who experienced at least one treatment emergent adverse event (TEAE) | From first dose to 8 weeks following last dose (Up to 24 weeks) | 
| Percentage of Participants Who Experienced at Least One Serious Treatment-emergent Adverse Event (STEAE) | This is the percentage of participants who experienced at least one serious treatment-emergent adverse event (STEAE) | From first dose to 8 weeks following last dose (Up to 24 weeks) |