Phase 2
N=21
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 · Left Ventricular Outflow Tract Obstruction
Bottom Line
View on ClinicalTrials.gov: NCT02842242 ↗Enrolled (actual)
21
Serious AEs
4.8%
Results posted
Feb 2020
Primary outcome: Primary: Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12 — -89.5; -25.0 mm Hg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MYK-461 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- MyoKardia, Inc.
- Primary completion
- Nov 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12 |
-89.5; -25.0 | — |
| SECONDARY Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg |
8; 0 | — |
| SECONDARY Change in Dyspnea Symptom Score From Baseline to Week 12 |
-3.1; -3.0 | — |
| SECONDARY Change in Peak VO2 From Baseline to Week 12 |
3.5; 1.7 | — |
| SECONDARY Change in VE/VCO2 From Baseline to Week 12 |
-2.2; -2.5 | — |
| SECONDARY Change in Resting LVEF From Baseline to Week 12 |
-14.6; -5.5 | — |
| SECONDARY Change in LV Fractional Shortening (LVFS) From Baseline to Week 12 |
-18.60; -3.98 | — |
| SECONDARY Change in Global Longitudinal Strain (GLS) From Baseline to Week 12 |
0.56; 0.18 | — |
| SECONDARY Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16 |
55.22; 84.08 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02842242). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.