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

NCT ID: NCT02842242

Last Updated: 2021-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2017-11-30

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.

Conditions

Cardiomyopathy, Hypertrophic Obstructive; Left Ventricular Outflow Tract Obstruction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open Label

MYK-461

Group Type: EXPERIMENTAL

MYK-461

Intervention Type: DRUG

Interventions

MYK-461

Intervention Type: DRUG

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.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MyoKardia, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amy Sehnert, MD

Role: STUDY_CHAIR

MyoKardia, Inc.

Locations

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Tufts Medical Center

Boston, Massachusetts, United States

Washington University St. Louis

St Louis, Missouri, United States

Duke Health Center at Southpoint

Durham, North Carolina, United States

Oregon Health and Science University

Portland, Oregon, United States

Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)

Philadelphia, Pennsylvania, United States

Countries

United States

References

Heitner SB, Jacoby D, Lester SJ, Owens A, Wang A, Zhang D, Lambing J, Lee J, Semigran M, Sehnert AJ. Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: A Clinical Trial. Ann Intern Med. 2019 Jun 4;170(11):741-748. doi: 10.7326/M18-3016. Epub 2019 Apr 30.

Reference Type: DERIVED

PMID: 31035291 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MYK-461-004

Identifier Type: -

Identifier Source: org_study_id