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

NCT02842242 | Completed Phase 2 Results

• 1 other identifier: MYK-461-004
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 7

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg

  Baseline and Week 12

• Change in Dyspnea Symptom Score From Baseline to Week 12

  Baseline and Week 12

• Change in Peak VO2 From Baseline to Week 12

  Baseline and Week 12

• Change in VE/VCO2 From Baseline to Week 12

  Baseline and Week 12

• Change in Resting LVEF From Baseline to Week 12

  Baseline and Week 12

Other Outcomes (4)

• Change in NYHA Functional Class From Baseline to Week 12

  Baseline and Week 12

• Change in KCCQ OSS From Baseline to Week 12

  Baseline and Week 12

• Change in NT-proBNP From Baseline to Week 12

  12 weeks

Study Arms (1)

Open Label

EXPERIMENTAL

MYK-461

Drug: MYK-461

Interventions

MYK-461 DRUG

Open Label

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• MyoKardia, Inc.: lead

Study Sites (7)

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, United States

Location

Tufts Medical Center

Boston, Massachusetts, United States

Location

Washington University St. Louis

St Louis, Missouri, United States

Location

Duke Health Center at Southpoint

Durham, North Carolina, United States

Location

Oregon Health and Science University

Portland, Oregon, United States

Location

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

Philadelphia, Pennsylvania, United States

Location

Related Publications (1)

• 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.

  PMID: 31035291 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic; Ventricular Outflow Obstruction, Left

Interventions

MYK-461

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction

Results Point of Contact

• Title: Dr. Amy Sehnert
• Organization: MyoKardia Inc.

asehnert@myokardia.com

650-741-7798

Study Officials

• Amy Sehnert, MD

  MyoKardia, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: July 22, 2016
• Study Start: August 1, 2016
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: June 8, 2021
• Results First Posted: February 5, 2020

Record last verified: 2021-06

Locations

US (7)