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

MyoKardia, Inc.7 sites in 1 country21 target enrollmentAugust 2016

ConditionsCardiomyopathy, Hypertrophic Obstructive Left Ventricular Outflow Tract Obstruction

InterventionsMYK-461

DrugsMYK-461

Overview

Phase: Phase 2
Intervention: MYK-461
Conditions: Cardiomyopathy, Hypertrophic Obstructive
Sponsor: MyoKardia, Inc.
Enrollment: 21
Locations: 7
Primary Endpoint: Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 2016

End Date

November 2017

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

MyoKardia, Inc.

Responsible Party

Sponsor

Eligibility Criteria

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

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.

Arms & Interventions

Open Label

MYK-461

Intervention: MYK-461

Outcomes

Primary Outcomes

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.

Secondary Outcomes

Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg(Baseline and Week 12)
Change in Peak VO2 From Baseline to Week 12(Baseline and Week 12)
Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16(Weeks 12 and 16)
Change in VE/VCO2 From Baseline to Week 12(Baseline and Week 12)
Change in LV Fractional Shortening (LVFS) From Baseline to Week 12(Baseline and Week 12)
Change in Global Longitudinal Strain (GLS) From Baseline to Week 12(Baseline and Week 12)
Change in Resting LVEF From Baseline to Week 12(Baseline and Week 12)
Change in Dyspnea Symptom Score From Baseline to Week 12(Baseline and Week 12)