Extension Study of Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Previously Enrolled in PIONEER

Phase 2

Completed

• Conditions: Hypertrophic Cardiomyopathy
• Interventions: Drug: mavacamten

• Registration Number: NCT03496168
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

This is a multicenter open-label study of the administration of mavacamten in participants with symptomatic obstructive HCM (oHCM) who previously participated in study MYK-461-004 (PIONEER-HCM).

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2018-04-05
• Study First Submitted QC: 2018-04-05
• Study First Posted: 2018-04-12
• Study Start: 2018-04-26
• Primary Completion: 2023-11-09
• Study Completion: 2023-11-09
• Results First Submitted: 2024-11-05
• Status Verified: 2025-01
• Results First Submitted QC: 2025-01-06
• Last Update Submitted: 2025-01-06
• Results First Posted: 2025-01-09
• Last Update Posted: 2025-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

• Completed Study MYK-461-004. Prior participation in a non-interventional observational study is allowed.
• Body weight > 45 kg at Screening
• Has safety laboratory parameters (chemistry and hematology) within normal limits

Key

Read More

Exclusion Criteria

• Has QTcF > > 500 ms or any other ECG abnormality considered by the investigator to pose a risk to subject safety (eg, second degree atrioventricular block type II)
• Since enrollment into Study MYK-461-004, has developed obstructive coronary artery disease (> 70% stenosis in one or more arteries) or known moderate or severe aortic valve stenosis
• Since enrollment into Study MYK-461-004, has developed any acute or serious comorbid condition (eg, major infection or hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction) that, in the opinion of the investigator or medical monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
• Since enrollment into Study MYK-461-004 has developed clinically significant malignant disease

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
mavacamten (MYK-461)	mavacamten	-

Primary Outcome Measures

Name	Time	Method
Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time	At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252	Post Valsalva left ventricular outflow tract (LVOT) gradient over time
Number of Participants With Treatment Emergent Adverse Events and Treatment Emergent Serious Adverse Events	From first dose to end of treatment + 56 days (Approximately an average of 240 Weeks)	AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment.; An SAE is defined as any untoward medical occurrence at any dose that: * Results in death; * Is immediately life-threatening (places the participant at immediate risk of death from the event as it occurred); * Requires inpatient hospitalization or prolongation of existing hospitalization; * Results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; * Results in a congenital abnormality or birth defect; * Is an important medical event that may not result in death, be life- threatening, or require hospitalization, but may be considered an SAE when, based upon appropriate medical judgment, it may require medical or surgical intervention to prevent any of the outcomes listed above.
Number of Participants Who Had Cardiovascular Death	From first dose to end of study, (approximately 260 weeks)	Number of participants who had died due to cardiovascular reasons.
Number of Participants Who Experienced Sudden Death	From first dose to end of study, (approximately 260 weeks)	Number of participants who experienced sudden death
Number of Participants Who Were Hospitalized for Cardiovascular Reasons.	From first dose to end of study, (approximately 260 weeks)	Number of participants who were hospitalized for cardiovascular reasons.
Number of Participants With Heart Failure Due to Systolic Dysfunction, Defined as Asymptomatic LVEF < 50%	From first dose to end of study, (approximately 260 weeks)	Number of participants with heart failure due to systolic dysfunction, defined as asymptomatic LVEF \< 50%
Number of Participants With LVEF < 50% as Measured by Echocardiography.	From first dose to end of study, (approximately 260 weeks)	Number of participants with LVEF \< 50% as measured by echocardiography.
Number of Participants Who Were Experienced Myocardial Infarction	From first dose to end of study, (approximately 260 weeks)	Number of participants who experienced myocardial infarction.
Number of Participants With Ventricular Arrhythmias.	From first dose to end of study, (approximately 260 weeks)	Types of Ventricular Arrhythmias measured in this endpoint will be: Ventricular Tachycardia Ventricular Fibrilation Ventricular Flutter
Number of Participants Who Experienced Syncope	From first dose to end of study, (approximately 260 weeks)	Number of participants who experienced syncope.; Syncope will be defined as participants who experienced dizziness or orthostatic hypotension.
Number of Participants Who Experienced Seizures	From first dose to end of study, (approximately 260 weeks)	Number of participants who were experienced seizures.
Number of Participants Who Were Experienced Strokes	From first dose to end of study, (approximately 260 weeks)	Number of participants who were experienced strokes.
Number of Participants With a Change in QT and QTcF Intervals.	From first dose to end of study, (approximately 260 weeks)	Number of participants with a change in QTcF intervals.; QTcF: An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula. QTc = QT/∛(RR/1000); RR = Respiration rate; QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec
Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time	At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252	Number of participants with changes of Post-exercise left ventricular outflow tract (LVOT) gradient over time
Resting Left Ventricular Outflow Tract (LVOT) Gradient Over Time	At Baseline, Week 4, Week 48, Week 72, Week 156, Week 204 and Week 252	Resting left ventricular outflow tract (LVOT) gradient over time
Participants With >= 1 NYHA Function Class Improvement	At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252	Participants with \>= 1 NYHA function class improvement.; The NYHA Functional Classification of heart failure assigns participants to 1 of 4 categories based on the participant's symptoms.; 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.
Mean Change From Baseline in the Overall KCCQ PRO Score.	At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252	The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a self-administered 23-item questionnaire questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. Overall KCCQ Pro score is the average of all the domains, symptom frequency and symptom burden scores, and transformed to a single score which ranged from 0 (worst) to 100 (the best possible status), where the higher score reflected better health status.
Mean Change From Baseline in Serum NT-proBNP.	At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252	Mean change from baseline in Serum N-terminal pro B-type natriuretic peptide levels.
Number of Participants Who Received Septal Reduction Therapy	252 weeks	Number of participants who received septal reduction therapy
Plasma Concentration of Mavacamen Overtime	At Baseline, Week 4, Week 8, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 156, Week 180, Week 204, Week 228 and Week 252	Plasma concentration of Mavacamen overtime

Trial Locations

Locations (4)

Local Institution - 0003; 🇺🇸 Scottsdale, Arizona, United States

Local Institution - 0001; 🇺🇸 New Haven, Connecticut, United States

Local Institution - 0004; 🇺🇸 Durham, North Carolina, United States

Local Institution - 0002; 🇺🇸 Portland, Oregon, United States