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

NCT03496168 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CV027-008
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 4

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).

Conditions

Hypertrophic Cardiomyopathy

Keywords

Symptomatic; Obstructive; Left ventricular outflow tract gradient

Outcome Measures

Primary Outcomes (20)

• 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

Study Arms (1)

mavacamten (MYK-461)

EXPERIMENTAL

Drug: mavacamten

Interventions

mavacamten DRUG

mavacamten capsules

Also known as: MYK-461

mavacamten (MYK-461)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (4)

Local Institution - 0003

Scottsdale, Arizona, 85259, United States

Location

Local Institution - 0001

New Haven, Connecticut, 06520-8017, United States

Location

Local Institution - 0004

Durham, North Carolina, 27710, United States

Location

Local Institution - 0002

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Masri A, Lester SJ, Stendahl JC, Hegde SM, Sehnert AJ, Balaratnam G, Shah A, Fox S, Wang A. Long-Term Safety and Efficacy of Mavacamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results of the PIONEER-OLE Study. J Am Heart Assoc. 2024 Apr 16;13(8):e030607. doi: 10.1161/JAHA.123.030607. Epub 2024 Apr 9.

  PMID: 38591260 DERIVED

Related Links

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

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

MYK-461

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

1-855-907-3286

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2018
• First Posted: April 12, 2018
• Study Start: April 26, 2018
• Primary Completion: November 9, 2023
• Study Completion: November 9, 2023
• Last Updated: January 9, 2025
• Results First Posted: January 9, 2025

Record last verified: 2025-01

Locations

US (4)