- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02842242
A Phase 2 Open-label Pilot Study Evaluating MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction (PIONEER-HCM)
June 3, 2021 updated by: MyoKardia, Inc.
A Phase 2 Open-label Pilot Study to Evaluate Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
The purpose of this phase 2 open-label pilot study is to evaluate the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of MYK-461 in subjects with symptomatic HCM and LVOT obstruction aged 18-70 years.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
21
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Arizona
-
Scottsdale, Arizona, United States
- Mayo Clinic Arizona
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Connecticut
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New Haven, Connecticut, United States
- Yale New Haven Hospital
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Massachusetts
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Boston, Massachusetts, United States
- Tufts Medical Center
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Missouri
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Saint Louis, Missouri, United States
- Washington University St. Louis
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North Carolina
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Durham, North Carolina, United States
- Duke Health Center at Southpoint
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Oregon
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Portland, Oregon, United States
- Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, United States
- Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Key Inclusion Criteria:
- Diagnosed with HCM (hypertrophied and non-dilated left ventricle in absence of systemic or other known cause), with LV wall thickness ≥ 15 mm at time of initial diagnosis or ≥ 13 mm with a positive family history of HCM.
- Age 18-70
- BMI 18-37kg/m2
- Documented LVEF ≥ 55% at the Screening visit as determined by the investigator and the investigational site's echocardiography laboratory.
- Resting LVOT gradient ≥ 30 mg Hg and post-exercise peak LVOT gradient ≥ 50 mm Hg
- NYHA functional class II or higher
Key Exclusion Criteria:
- History of sustained ventricular tachyarrhythmia.
- History of syncope with exercise within past 6 months.
- Active infection.
- Persistent atrial fibrillation or atrial fibrillation at Screening or history of paroxysmal atrial fibrillation with resting rate document > 100bpm within 1 year of screening.
- Has QTc Fridericia (QTcF) > 500 ms, or any other ECG abnormality considered by the investigator to pose a risk to subject safety (e.g. second degree atrioventricular block type II).
- Aortic stenosis or fixed subaortic obstruction.
- History of LV systolic dysfunction (LVEF < 45%) at any time during their clinical course.
- History of obstructive coronary artery disease.
- History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator or MyoKardia physician, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
- Part A: Ongoing therapy with beta blockers, calcium channel blockers, or disopyramide. Subjects on any of these medications who, in the opinion of the investigator, can safely be withdrawn are eligible as long as medication is discontinued at least 14 days prior to the Screening visit.
- Part B: Ongoing therapy with calcium channel blockers or disopyramide. Subjects on any of these medications who, in the opinion of the investigator, can safely be withdrawn are eligible as long as medication is discontinued at least 14 days prior to the Screening visit.
- Prior treatment with cardiotoxic agents such as doxorubicin or similar, or current treatment with antiarrhythmic drugs that have negative inotropic activity, e.g. flecainide or propafenone.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Open Label
MYK-461
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12
Time Frame: Baseline and Week 12
|
Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
|
Baseline and Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg
Time Frame: Baseline and Week 12
|
LVOT gradients are assessed after a treadmill stress test by echocardiography.
|
Baseline and Week 12
|
Change in Dyspnea Symptom Score From Baseline to Week 12
Time Frame: Baseline and Week 12
|
The scale name is Dyspnea Numeric Rating Scale (NRS).
It is intended to measure how much shortness of breath you have had in the past week.
0 = no shortness of breath and 10 = shortness of breath as the worst possible.
|
Baseline and Week 12
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Change in Peak VO2 From Baseline to Week 12
Time Frame: Baseline and Week 12
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Peak VO2 is assessed using a cardiopulmonary exercise test.
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Baseline and Week 12
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Change in VE/VCO2 From Baseline to Week 12
Time Frame: Baseline and Week 12
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VE/VCO2 is assessed from cardiopulmonary exercise testing results.
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Baseline and Week 12
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Change in Resting LVEF From Baseline to Week 12
Time Frame: Baseline and Week 12
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LVEF is assessed by echocardiography.
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Baseline and Week 12
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Change in LV Fractional Shortening (LVFS) From Baseline to Week 12
Time Frame: Baseline and Week 12
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LVFS is assessed using echocardiography measures.
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Baseline and Week 12
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Change in Global Longitudinal Strain (GLS) From Baseline to Week 12
Time Frame: Baseline and Week 12
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GLS is assessed using echocardiography measures.
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Baseline and Week 12
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Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16
Time Frame: Weeks 12 and 16
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Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
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Weeks 12 and 16
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in NYHA Functional Class From Baseline to Week 12
Time Frame: Baseline and Week 12
|
Baseline and Week 12
|
|
Change in KCCQ OSS From Baseline to Week 12
Time Frame: Baseline and Week 12
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Baseline and Week 12
|
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Change in NT-proBNP From Baseline to Week 12
Time Frame: 12 weeks
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12 weeks
|
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Number of Subjects Achieving an LVOT Gradient Response of Post-exercise Peak Gradient < 10 mmHg at Week 12
Time Frame: Baseline and Week 12
|
Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
|
Baseline and Week 12
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Amy Sehnert, MD, MyoKardia, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 1, 2016
Primary Completion (Actual)
November 1, 2017
Study Completion (Actual)
November 1, 2017
Study Registration Dates
First Submitted
July 20, 2016
First Submitted That Met QC Criteria
July 20, 2016
First Posted (Estimate)
July 22, 2016
Study Record Updates
Last Update Posted (Actual)
June 8, 2021
Last Update Submitted That Met QC Criteria
June 3, 2021
Last Verified
June 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MYK-461-004
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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