This is a randomized, double-blind, placebo-controlled, multi-center study in the United States (U.S.) that will evaluate the effect of mavacamten treatment on reducing the number of septal reduction therapy (SRT) procedures performed in subjects with symptomatic obstructive hypertrophic cardiomyopathy (oHCM \[also known as HOCM\]) who are eligible for SRT based on ACCF/AHA 2011 and/or ESC 2014 guidelines.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
112
Mavacamten Capsules Other names: MYK-461
Placebo
Local Institution - 0009
Los Angeles, California, United States
Composite of Decision to Proceed With Septal Reduction Therapy (SRT) and SRT Guideline Eligible at Week 16
Participants who decided to proceed with SRT or were eligible for SRT at week 16. Participants with missing assessments were classified as meeting the primary endpoint (did not improve). SRT eligibility using the New York Heart Association Functional Class (NYHA) and left ventricular outflow tract (LVOT) assessments per the 2011 ACCF/AHA guideline clinical and hemodynamic criterion are below: * NYHA Class III or IV/ NYHA Class II with exertion-induced syncope/near syncope, AND * Dynamic LVOT gradient at rest or with provocation \>= 50 mmHg. NYHA Class II at week 16, the following rules will be applied: * NYHA Class II with history of exertional syncope/ syncope at baseline and at W16 is still NYHA Class II, they remain SRT eligible IF their maximal LVOT gradient is ≥ 50mmHg * NYHA Class III/IV at baseline and at W16 has improved to Class II, they are no longer SRT eligible UNLESS they have AE of exertional syncope or pre-syncope during the 16 weeks.
Time frame: Week 16
Number of Participants With at Least One Class Improvement From Baseline in New York Heart Association (NYHA) Class at Week 16
The NYHA functional classification of heart failure assigns participants to 1 of 4 categories based on the participants symptoms. Baseline values are defined generally as the last available value before the first administration of study drug of analysis interest. Participants with missing NYHA class assessments are treated as no improvement. Class 1: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). Class 2: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). Class 3: Marked limitation of physical activity. Comfortable at rest. Less-than ordinary-activity causes fatigue, palpitation, or dyspnea. Class 4: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.
Time frame: Baseline and week 16
Change From Baseline to Week 16 in Kansas City Cardiomyopathy Questionnaire 23-item Version, Clinical Summary Score (KCCQ-23, CSS)
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Local Institution - 0011
Stanford, California, United States
Local Institution - 0001
New Haven, Connecticut, United States
Local Institution - 0021
Weston, Florida, United States
Local Institution - 0016
Boston, Massachusetts, United States
Local Institution - 0007
Boston, Massachusetts, United States
Local Institution - 0006
Ann Arbor, Michigan, United States
Local Institution - 0013
Grand Rapids, Michigan, United States
Local Institution - 0015
Rochester, Minnesota, United States
Local Institution - 0005
St Louis, Missouri, United States
...and 11 more locations
The KCCQ-23 is a 23-item, self-administered questionnaire that measures the impact of a participant's cardiovascular disease or its treatment on 6 distinct domains using a 2-week recall period: symptoms/signs, physical limitation, quality of life (QoL), social limitations, self-efficacy, and symptom stability. The KCCQ 23 Clinical Summary Score (CSS) is derived from the Total Symptom Score (TSS) and the Physical Limitations (PL) score of the KCCQ 23. The CSS, TSS, and the PL score range from 0 to 100 with higher scores representing less severe symptoms and/or physical limitations. The CSS is a mean of the TSS and the PL score.
Time frame: Baseline and week 16
Change From Baseline to Week 16 in N-Terminal Pro-b-Type Natriuretic Peptide (NT-proBNP)
A geometric mean ratio was used to assess the change from baseline to Week 16 in N-Terminal Pro-b-Type Natriuretic Peptide (NT-proBNP). Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.
Time frame: Baseline and week 16
Change From Baseline to Week 16 in Cardiac Troponin
A geometric mean ratio was used to assess the change from baseline to week 16 in cardiac troponin. Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.
Time frame: Baseline and week 16
Change From Baseline to Week 16 in Post-Exercise Left Ventricular Outflow Tract (LVOT) Gradient
Change from baseline to week 16 in post-exercise left ventricular outflow tract (LVOT) gradient. Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.
Time frame: Baseline and week 16