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

• Register: ClinicalTrials.gov
• Last refreshed on: 14 June 2021
• Main ID: NCT02842242
• Date of registration: 20/07/2016
• Prospective Registration: Yes
• Primary sponsor: MyoKardia, Inc.
• Public title: A Phase 2 Open-label Pilot Study Evaluating MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction PIONEER-HCM
• Scientific 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
• Date of first enrolment: August 2016
• Target sample size: 21
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02842242
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Amy Sehnert, MD
• Affiliation: MyoKardia, Inc.

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Left Ventricular Outflow Tract Obstruction

Cardiomyopathy, Hypertrophic Obstructive

Intervention(s)

Drug: MYK-461

Primary Outcome(s)

Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12 [Time Frame: Baseline and Week 12]

Secondary Outcome(s)

Change in Peak VO2 From Baseline to Week 12 [Time Frame: Baseline and Week 12]

Change in LV Fractional Shortening (LVFS) From Baseline to Week 12 [Time Frame: Baseline and Week 12]

Change in VE/VCO2 From Baseline to Week 12 [Time Frame: Baseline and Week 12]

Change in Resting LVEF From Baseline to Week 12 [Time Frame: Baseline and Week 12]

Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg [Time Frame: Baseline and Week 12]

Change in Dyspnea Symptom Score From Baseline to Week 12 [Time Frame: Baseline and Week 12]

Change in Global Longitudinal Strain (GLS) From Baseline to Week 12 [Time Frame: Baseline and Week 12]

Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16 [Time Frame: Weeks 12 and 16]

Secondary ID(s)

MYK-461-004

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/02/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02842242