MYK-224 in Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction

What is the Purpose of this Study?

The purpose of this study is to examine the safety and effectiveness of an investigational drug called MYK-224 in individuals with obstructive hypertrophic cardiomyopathy (oHCM). The amount of MYK-224 that reaches the blood stream and the relationship of MYK-224 in the blood stream to any observed effects (such as reduction of outflow obstruction) on the heart will also be evaluated. Researchers will assess the effects of multiple doses in each participant and use individualized dose adjustments based on safety measures and effects on the heart. Participants will begin at a dose of 5 mg of MYK-224. After taking this dose for at least 21 days, they will return to the study site for a series of heart assessments. Based on the results of these assessments, the dose may be increased, decreased, or stay the same. All participants will receive treatment with MYK-224 (also known as BMS 986435).

Eligibility

* 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.

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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A Phase 2a, Open-label, Pilot Study to Evaluate Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of MYK-224 in Participants with Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction

Study Details

Disease Type/Condition

Other

Principal Investigator

Rader, Florian

Age Group

Adult

Phase

IRB Number

STUDY00002324

ClinicalTrials.gov ID

NCT05556343

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org