A Study of Mavacamten in Obstructive Hypertrophic Cardiomyopathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness, safety, and tolerability of a 30-week course of mavacamten and the long-term effects of mavacamten in Japanese participants with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

Official Title
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A Phase 3, Open-label, Single Arm, Clinical Study to Evaluate Efficacy, Safety and Tolerability of Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Conditions
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Cardiomyopathy, Hypertrophic Obstructive

Intervention / Treatment
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* Drug: Mavacamten


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 and greater, body weight ≥ 35kg Has adequate acoustic windows to enable accurate transthoracic echocardiograms (TTEs) Diagnosed with obstructive hypertrophic cardiomyopathy consistent with current American College of Cardiology Foundation/American Heart Association, European Society of Cardiology, and Japanese Circulation Society guidelines Has documented left ventricular ejection fraction (LVEF) ≥60% NYHA Class II or III 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 atrial fibrillation with atrial fibrillation present at the time of 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 cibenzoline, disopyramide or ranolazine Treatment (within 14 days prior to Screening) or planned treatment during the study with a combination of beta blockers and verapamil or a combination of beta blockers and diltiazem 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 Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mavacamten<br> | Drug: Mavacamten<br>* Specified dose on specified days<br>* Other names: MYK-461;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 30 in post exercise left ventricular outflow tract (LVOT) peak gradient as determined by Doppler echocardiography |  | Up to Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 30 in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS) | The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a patient reported outcome instrument with minimum score = 0 and maximum score = 100 where higher score indicates better health status. The instrument utilizes a recall period of 2 weeks over which patients describe the frequency and severity of their symptoms, their physical and social limitations, and how they perceive their heart failure symptoms to affect their quality of life. The KCCQ clinical summary score (KCCQ-CSS) combines the physical limitation and total symptom scores. | Up to Week 30 | 
| Proportion of participants with at least 1 class improvement in New York Heart Association (NYHA) functional class from baseline to Week 30 | The New York Heart Association (NYHA) functional classification of heart failure assigns participants to 1 of 4 categories based on the participant's symptoms. Heart failure classification will be assessed by the Investigator at specified timepoints in the study. NYHA class at Week 30 will be compared to baseline and the proportion of participants with an improvement of at least one class will be determined. | Up to Week 30 | 
| Change from baseline to Week 30 in N-terminal pro b-type natriuretic peptide (NT-proBNP) |  | Up to Week 30 | 
| Change from baseline to Week 30 in cardiac troponins |  | Up to Week 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mavacamten, Obstructive Hypertrophic Cardiomyopathy (HCM)