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

Trial Purpose and Description

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.

Ages: 18 - 70 years

Gender: Both

Eligibility 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.
  • 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 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.
  • 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 Subjects on any of these medications who, in the opinion of the investigator, can safely be withdrawn are eligible as long as medication is discontinued at least 14 days prior to the Screening visit.
  • 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.

MyoKardia, Inc.

Dates: 10/07/2016 - 05/31/2017

Last Updated: 10/08/2016

Study HIC#: 2000020006

Get Involved

For more information about this study, contact:
Christina L Williams
+1 203-737-6407

If you would prefer to contact a member of the Help us Discover team about this trial and other similar trials, please email helpusdiscover@yale.edu or call 1-877-978-8348.

Trial Image


Daniel Louis Jacoby

Principal Investigator