A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and efficacy of mavacamten compared with placebo in participants with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM).

Official Title
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A Randomized, Double-blind, Placebo-controlled Clinical Study to Evaluate Mavacamten in Adults With Symptomatic Non-obstructive Hypertrophic Cardiomyopathy

Conditions
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Cardiomyopathy, Hypertrophic

Intervention / Treatment
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* Drug: Mavacamten
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines: unexplained left-ventricular hypertrophy with non-dilated ventricular chambers in the absence of other cardiac or systemic disease which can produce the required magnitude of hypertrophy of a maximal left ventricular (LV) wall thickness ≥ 15 millimeters (mm) (or ≥ 13 mm with positive family history of hypertrophic cardiomyopathy [HCM]) as determined by core laboratory interpretation Peak left ventricular outflow tract (LVOT) pressure gradient < 30 millimeters mercury (mm Hg) at rest and < 50 mm Hg with provocation (Valsalva maneuver and stress echocardiography) New York Heart Association (NYHA) Class II or III Exclusion Criteria: Known infiltrative or storage disorder causing cardiac hypertrophy that mimics non-obstructive hypertrophic cardiomyopathy (nHCM) such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy History of unexplained syncope within 6 months prior to screening History of sustained ventricular tachyarrhythmia (> 30 seconds) within 6 months prior to screening Additional inclusion and 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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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Kansas City Cardiomyopathy Questionnaire (23-item) Clinical Summary Score (KCCQ-23 CSS) at Week 48 |  | Up to Week 48 | 
| Change from baseline in peak oxygen consumption (pVO2) at Week 48 |  | Up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ventilatory efficiency (VE/VCO2) slope to Week 48 |  | Up to Week 48 | 
| Proportion of participants with at least 1 class of New York Heart Association (NYHA) improvement from baseline to Week 48 |  | Up to Week 48 | 
| Change from baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP) to Week 48 |  | Up to Week 48 | 
| Change from baseline in cardiac troponin-T (cTn-T) to Week 48 |  | Up to Week 48 | 
| Change from baseline in hypertrophic cardiomyopathy symptom questionnaire-shortness of breath (HCMSQ-SoB) domain to Week 48 |  | Up to Week 48 | 
| Time to first major adverse cardiovascular events (MACE)-plus events | Defined as any cardiovascular (CV) death, nonfatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, hospitalization for arrhythmias, or appropriate implantable cardioverter defibrillator (ICD) therapy | Up to 120 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mavacamten, non-obstructive HCM, non-obstructive hypertrophic cardiomyopathy (nHCM)