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

An Open-Label Extension Study of Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Previously Enrolled in Study MYK-461-004 (PIONEER)

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).

Study Overview

• Status: Completed
• Conditions: Hypertrophic Cardiomyopathy
• Intervention / Treatment: Drug: mavacamten

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Local Institution - 0003
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8017
      • Local Institution - 0001
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0004
  • Oregon
    • Portland, Oregon, United States, 97239
      • Local Institution - 0002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mavacamten (MYK-461)	Drug: mavacamten; mavacamten capsules; Other Names: MYK-461

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events and Treatment Emergent Serious Adverse Events	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.	From first dose to end of treatment + 56 days (Approximately an average of 240 Weeks)
Number of Participants Who Had Cardiovascular Death	Number of participants who had died due to cardiovascular reasons.	From first dose to end of study, (approximately 260 weeks)
Number of Participants Who Experienced Sudden Death	Number of participants who experienced sudden death	From first dose to end of study, (approximately 260 weeks)
Number of Participants Who Were Hospitalized for Cardiovascular Reasons.	Number of participants who were hospitalized for cardiovascular reasons.	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 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 LVEF < 50% as Measured by Echocardiography.	Number of participants with LVEF < 50% as measured by echocardiography.	From first dose to end of study, (approximately 260 weeks)
Number of Participants Who Were Experienced Myocardial Infarction	Number of participants who experienced myocardial infarction.	From first dose to end of study, (approximately 260 weeks)
Number of Participants With Ventricular Arrhythmias.	Types of Ventricular Arrhythmias measured in this endpoint will be: Ventricular Tachycardia Ventricular Fibrilation Ventricular Flutter	From first dose to end of study, (approximately 260 weeks)
Number of Participants Who Experienced Syncope	Number of participants who experienced syncope. Syncope will be defined as participants who experienced dizziness or orthostatic hypotension.	From first dose to end of study, (approximately 260 weeks)
Number of Participants Who Experienced Seizures	Number of participants who were experienced seizures.	From first dose to end of study, (approximately 260 weeks)
Number of Participants Who Were Experienced Strokes	Number of participants who were experienced strokes.	From first dose to end of study, (approximately 260 weeks)
Number of Participants With a Change in QT and QTcF Intervals.	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	From first dose to end of study, (approximately 260 weeks)
Post-exercise Left Ventricular Outflow Tract (LVOT) Gradient Over Time	Number of participants with changes of 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
Resting 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
Post Valsalva Left Ventricular Outflow Tract (LVOT) Gradient Over Time	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
Participants With >= 1 NYHA Function Class Improvement	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.	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 the Overall KCCQ PRO Score.	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.	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 NT-proBNP.	Mean change from baseline in Serum N-terminal pro B-type natriuretic peptide levels.	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
Number of Participants Who Received Septal Reduction Therapy	Number of participants who received septal reduction therapy	252 weeks
Plasma Concentration of Mavacamen Overtime	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2018
• Primary Completion (Actual): November 9, 2023
• Study Completion (Actual): November 9, 2023

Study Registration Dates

• First Submitted: April 5, 2018
• First Submitted That Met QC Criteria: April 5, 2018
• First Posted (Actual): April 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Symptomatic; Obstructive; Left ventricular outflow tract gradient
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Diseases; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Hypertrophy
• Other Study ID Numbers: CV027-008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No