Clinical trial NCT02842242: A Phase 2 Open-label Pilot Study Evaluating MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiomyopathy, Hypertrophic Obstructive
Left Ventricular Outflow Tract Obstruction
Lead sponsor: MyoKardia, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg
timeFrame: Baseline and Week 12
measure: Change in Dyspnea Symptom Score From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Peak VO2 From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in VE/VCO2 From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Resting LVEF From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in LV Fractional Shortening (LVFS) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Global Longitudinal Strain (GLS) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16
timeFrame: Weeks 12 and 16
Other outcomes:
measure: Change in NYHA Functional Class From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in KCCQ OSS From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in NT-proBNP From Baseline to Week 12
timeFrame: 12 weeks
measure: Number of Subjects Achieving an LVOT Gradient Response of Post-exercise Peak Gradient < 10 mmHg at Week 12
timeFrame: Baseline and Week 12
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Durham
country: United States
facility: Duke Health Center at Southpoint
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)
state: Pennsylvania
Study officials:
affiliation: MyoKardia, Inc.
name: Amy Sehnert, MD
role: STUDY_CHAIR
References:
citation: 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.