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A Phase 2 Open-label Pilot Study Evaluating MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction (PIONEER-HCM)

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ClinicalTrials.gov Identifier: NCT02842242
Recruitment Status : Completed
First Posted : July 22, 2016
Last Update Posted : January 29, 2019
Sponsor:
Information provided by (Responsible Party):
MyoKardia, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cardiomyopathy, Hypertrophic Obstructive Drug: MYK-461 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 2016
Actual Primary Completion Date : November 2017
Actual Study Completion Date : November 2017


Arm Intervention/treatment
Experimental: Open Label
MYK-461
Drug: MYK-461



Primary Outcome Measures :
  1. Change in post-exercise peak LVOT gradient from baseline to Week 12 [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Proportion of subjects achieving an LVOT gradient response of post-exercise peak gradient < 30 mmHg [ Time Frame: 12 weeks ]
  2. Change in dyspnea symptom score from baseline to Week 12 [ Time Frame: 12 weeks ]
  3. Change in pVO2 and VE/VCO2 from baseline to Week 12 [ Time Frame: 12 weeks ]
  4. Change in LVEF (2 dimensional [2D]and 3 dimensional ([3D]), global longitudinal strain (GLS), and LV fractional shortening (LVFS) from baseline to Week 12 [ Time Frame: 12 weeks ]
  5. Change in post-exercise peak LVOT gradient from Week 12 to Week 16 [ Time Frame: 4 weeks ]
  6. Plasma PK profile of mavacamten [ Time Frame: 16 weeks ]

Other Outcome Measures:
  1. Proportion of subjects achieving an LVOT gradient response of post-exercise peak gradient < 10 mmHg at Week 12 [ Time Frame: 12 weeks ]
  2. Change in NYHA functional class from baseline to Week 12 [ Time Frame: 12 weeks ]
  3. Change in NT-proBNP from baseline to Week 12 [ Time Frame: 12 weeks ]
  4. Change in KCCQ OSS from baseline to Week 12 [ Time Frame: 12 weeks ]
  5. Change from baseline in arterial pulse wave morphology assessed using an optical biosensor [ Time Frame: 12 weeks ]
  6. Change from baseline in HR and heart rhythm assessed using a cardiac monitoring skin patch [ Time Frame: 12 weeks ]


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02842242


Locations
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United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States
United States, Connecticut
Yale New Haven Hospital
New Haven, Connecticut, United States
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States
United States, Missouri
Washington University St. Louis
Saint Louis, Missouri, United States
United States, North Carolina
Duke Health Center at Southpoint
Durham, North Carolina, United States
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States
United States, Pennsylvania
Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
MyoKardia, Inc.
Investigators
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Study Chair: Amy Sehnert, MD MyoKardia, Inc.

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Responsible Party: MyoKardia, Inc.
ClinicalTrials.gov Identifier: NCT02842242     History of Changes
Other Study ID Numbers: MYK-461-004
First Posted: July 22, 2016    Key Record Dates
Last Update Posted: January 29, 2019
Last Verified: December 2018

Additional relevant MeSH terms:
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Cardiomyopathies
Hypertrophy
Cardiomyopathy, Hypertrophic
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases