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

Cardiomyopathy, Hypertrophic Obstructive Clinical Trial

— PIONEER-HCM  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02842242
• Other study ID #: MYK-461-004
• Status: Completed
• Phase: Phase 2
• Start date: August 2016
• Est. completion date: November 2017

Study information

• Verified date: June 2021
• Source: MyoKardia, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Cardiomyopathy, Hypertrophic Obstructive
• Hypertrophy
• Left Ventricular Outflow Tract Obstruction

Intervention

Drug:
• MYK-461

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts
United States	Duke Health Center at Southpoint	Durham	North Carolina
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University St. Louis	Saint Louis	Missouri
United States	Mayo Clinic Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
MyoKardia, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in NYHA Functional Class From Baseline to Week 12		Baseline and Week 12
Other	Change in KCCQ OSS From Baseline to Week 12		Baseline and Week 12
Other	Change in NT-proBNP From Baseline to Week 12		12 weeks
Other	Number of Subjects Achieving an LVOT Gradient Response of Post-exercise Peak Gradient < 10 mmHg at Week 12	Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.	Baseline and Week 12
Primary	Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12	Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.	Baseline and Week 12
Secondary	Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg	LVOT gradients are assessed after a treadmill stress test by echocardiography.	Baseline and Week 12
Secondary	Change in Dyspnea Symptom Score From Baseline to 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
Secondary	Change in Peak VO2 From Baseline to Week 12	Peak VO2 is assessed using a cardiopulmonary exercise test.	Baseline and Week 12
Secondary	Change in VE/VCO2 From Baseline to Week 12	VE/VCO2 is assessed from cardiopulmonary exercise testing results.	Baseline and Week 12
Secondary	Change in Resting LVEF From Baseline to Week 12	LVEF is assessed by echocardiography.	Baseline and Week 12
Secondary	Change in LV Fractional Shortening (LVFS) From Baseline to Week 12	LVFS is assessed using echocardiography measures.	Baseline and Week 12
Secondary	Change in Global Longitudinal Strain (GLS) From Baseline to Week 12	GLS is assessed using echocardiography measures.	Baseline and Week 12
Secondary	Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16	Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.	Weeks 12 and 16