A Study of Mavacamten in Obstructive Hypertrophic Cardiomyopathy

Phase 3

Active, not recruiting

Conditions: Cardiomyopathy, Hypertrophic Obstructive

Interventions: Drug: Mavacamten

Registration Number: NCT05414175

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 38

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Mavacamten	Mavacamten	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Post-exercise Left Ventricular Outflow Tract (LVOT) Peak Gradient at Week 30	At Baseline and Week 30	The post-exercise LVOT gradient was measured from echocardiograms obtained at baseline and week 30 following a study-specified exercise protocol and read by the doppler echocardiography. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Kansas City Cardiomyopathy Questionnaire 23-item Version (KCCQ-23) Clinical Summary Score (CSS) at Week 30	At Baseline and Week 30	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. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.
Percentage of Participants With at Least 1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 30	Baseline and at Week 30	The NYHA Functional Classification of Heart Failure (HF) assigns participants to 1 of 4 categories based on the participant's symptoms. Class I (No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea); Class II (Slight limitation of physical activity, Comfortable at rest, Ordinary physical activity results in fatigue, palpitation, dyspnea); Class III (Marked limitation of physical activity, Comfortable at rest, Less-than ordinary-activity causes fatigue, palpitation, or dyspnea) and Class IV (Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases). Improvement is defined as participant moving to lower class category from a higher one. Baseline is defined as last non-missing measurement prior to the first dose.
Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 30	At baseline and week 30	Blood samples were collected for assessing the concentration of NT-proBNP. Baseline is defined as last non-missing measurement prior to the first dose.
Change From Baseline in Cardiac Troponin I at Week 30	At baseline and week 30	Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.
Change From Baseline in Cardiac Troponin T at Week 30	At baseline and week 30	Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.

Trial Locations

Locations (20): Local Institution - 0026
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Himeji-Shi, Hyogo, Japan
Local Institution - 0020
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Uwajima, Ehime, Japan
Local Institution - 0016
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Kobe-shi, Hyogo, Japan
Local Institution - 0017
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Tsukuba-Shi, Ibaraki, Japan
Local Institution - 0023
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Kanazawa-shi, Ishikawa, Japan
Local Institution - 0019
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Yokohama, Kanagawa, Japan
Local Institution - 0015
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Nankoku-shi, Kochi, Japan
Local Institution - 0028
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Tsu-Shi, MIE, Japan
Local Institution - 0027
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Sendai, Miyagi, Japan
Local Institution - 0011
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Suita-Shi, Osaka, Japan
Local Institution - 0012
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Hamamatsu-city, Shizuoka, Japan
Local Institution - 0014
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Suita, Osaka, Japan
Local Institution - 0010
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Bunkyo-Ku, Tokyo, Japan
Local Institution - 0009
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Chuo-Ku, Tokyo, Japan
Local Institution - 0003
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Fuchu-Shi, Tokyo, Japan
Local Institution - 0001
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Itabashi-Ku, Tokyo, Japan
Local Institution - 0005
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Shinjuku-Ku, Tokyo, Japan
Local Institution - 0007
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Koto-Ku, Tokyo, Japan
Local Institution - 0013
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Shinjuku-ku, Tokyo, Japan
Local Institution - 0018
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Osaka, Japan