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

Phase 2

Completed

• Conditions: Left Ventricular Outflow Tract Obstruction; Cardiomyopathy, Hypertrophic Obstructive
• Interventions: Drug: MYK-461

• Registration Number: NCT02842242
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-07-20
• Study First Submitted QC: 2016-07-20
• Study First Posted: 2016-07-22
• Study Start: 2016-08
• Primary Completion: 2017-11
• Study Completion: 2017-11
• Disposition First Submitted: 2018-11-19
• Disposition First Submitted QC: 2018-11-19
• Disposition First Posted: 2018-11-21
• Results First Submitted: 2020-01-08
• Results First Submitted QC: 2020-01-23
• Results First Posted: 2020-02-05
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-03
• Last Update Posted: 2021-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open Label	MYK-461	MYK-461

Primary Outcome Measures

Name	Time	Method
Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12	Baseline and Week 12	Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg	Baseline and Week 12	LVOT gradients are assessed after a treadmill stress test by echocardiography.
Change in Peak VO2 From Baseline to Week 12	Baseline and Week 12	Peak VO2 is assessed using a cardiopulmonary exercise test.
Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16	Weeks 12 and 16	Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
Change in VE/VCO2 From Baseline to Week 12	Baseline and Week 12	VE/VCO2 is assessed from cardiopulmonary exercise testing results.
Change in LV Fractional Shortening (LVFS) From Baseline to Week 12	Baseline and Week 12	LVFS is assessed using echocardiography measures.
Change in Global Longitudinal Strain (GLS) From Baseline to Week 12	Baseline and Week 12	GLS is assessed using echocardiography measures.
Change in Resting LVEF From Baseline to Week 12	Baseline and Week 12	LVEF is assessed by echocardiography.
Change in Dyspnea Symptom Score From Baseline to Week 12	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.

Trial Locations

Locations (7)

Mayo Clinic Arizona; 🇺🇸 Scottsdale, Arizona, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Washington University St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Hospital of the University of Pennsylvania (Penn Heart and Vascular Center); 🇺🇸 Philadelphia, Pennsylvania, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Duke Health Center at Southpoint; 🇺🇸 Durham, North Carolina, United States