A Study to Evaluate the Efficacy, Safety, and Tolerability of MYK-224 in Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
Purpose
The purpose of this study is to characterize the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of MYK-224 in participants with obstructive Hypertrophic Cardiomyopathy (oHCM)
Condition
- Cardiomyopathy, Hypertrophic
Eligibility
- Eligible Ages
- Between 18 Years and 80 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Has adequate acoustic windows, to enable accurate TTEs as determined by the echocardiography core laboratory. - Men or women diagnosed with oHCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines, satisfying both of the following criteria: - Has unexplained left ventricular (LV) hypertrophy with nondilated ventricular chambers in the absence of other cardiac (eg, hypertension, aortic stenosis) or systemic disease and with maximal LV wall thickness ≥ 15 millimeter (mm) (or ≥ 13 mm with positive family history of hypertrophic cardiomyopathy or with a known disease-causing mutation), as determined by core laboratory interpretation. AND -- Has a LVOT peak gradient during screening as assessed by echocardiography of ≥ 50 millimeters of mercury (mm Hg) at rest, or ≥ 30 mm Hg at rest and ≥ 50 mm Hg with Valsalva maneuver (confirmed by echocardiography core laboratory interpretation). - Has resting LVEF ≥ 60% at the Screening visit as determined by echocardiography core laboratory. - New York Heart Association (NYHA) functional class II or III symptoms at screening. - Has a valid measurement of LVOT post-exercise peak gradient at screening as determined by echocardiography core laboratory.
Exclusion Criteria
- Presence of any medical condition that precludes exercise stress testing. - History of syncope or sustained ventricular tachyarrhythmia within 6 months prior to screening. - Known infiltrative or storage disorder causing cardiac hypertrophy that mimics HCM, such as Fabry disease, amyloidosis, or Noonan syndrome with left ventricular hypertrophy. - Prior treatment with mavacamten or aficamten. An exception may be made in cases where myosin inhibitor use was not within 4 months of the Screening visit, and with the agreement of both the Investigator and the Medical Monitor. - Has been successfully treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation [ASA]) within 6 months prior to Screening or plans to have either of these treatments during the study (Note: Individuals with an unsuccessful myectomy or percutaneous ASA procedure performed > 6 months prior to Screening may be enrolled if study eligibility criteria for LVOT gradient criteria are met). - Implantable cardioverter-defibrillator (ICD) placement or pulse generator change within 2 months prior to screening or planned new ICD placement during the study (pulse generator changes, if needed during the study are allowed). - Has a history of resuscitated sudden cardiac arrest (any time) or known history of appropriate implantable cardioverter-defibrillator (ICD discharge for life-threatening ventricular arrhythmia within 6 months prior to screening. - Has paroxysmal, atrial fibrillation with atrial fibrillation present per the Investigator's evaluation of the participant's ECG at the time of Screening. - Has persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to Screening and/or not adequately rate controlled within 6 months prior to Screening (Note: Participants with persistent or permanent atrial fibrillation who are anticoagulated and adequately rate-controlled are allowed). - Has QT interval with Fridericia correction (QTcF) > 500 msec when QRS interval < 120 msec or QTcF > 520 msec when QRS ≥ 120 msec if participant has left bundle branch block or any other 12-lead ECG abnormality considered by the investigator to pose a risk to participant safety (eg, second-degree atrioventricular block type II). - Has known moderate or severe (per investigator's judgment) aortic valve stenosis at screening. - History of LV systolic dysfunction (LVEF < 45%) at any time during their clinical course. - Clinically significant pulmonary disease associated with exertional dyspnea. - Has known significant unrevascularized obstructive coronary artery disease (>70% stenosis in one or more main epicardial coronary arteries) or history of myocardial infarction Note: participants with prior coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCIs) are allowed if the procedure was performed at least 12 weeks prior to screening - Prior treatment with cardiotoxic agents such as anthracyclines (eg, doxorubicin) or similar Other protocol-defined criteria apply.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Cohort 1 |
Participants will receive MYK-224 either as a monotherapy or in combination with standard-of-care consisting of a beta-blocker. Participants who complete Cohort 1 will be eligible for an optional open label extension period |
|
|
Experimental Cohort 2 |
Participants will receive MYK-224 in combination with standard-of-care consisting of either a calcium channel blocker or disopyramide (which is given in combination with either a beta-blocker or calcium channel blocker). Participants who complete Cohort 2 will be eligible for an optional open label extension period |
|
Recruiting Locations
University of Kansas Medical Center (KUMC)
Kansas City, Kansas 66103-2937
Kansas City, Kansas 66103-2937
Contact:
Loren Berenbom, Site 0001
+910771569
Loren Berenbom, Site 0001
+910771569
More Details
- Status
- Recruiting
- Sponsor
- Bristol-Myers Squibb
Study Contact
BMS Study Connect Contact Center www.BMSStudyConnect.com855-907-3286
Clinical.Trials@bms.com