Multiple Dose Study to Evaluate Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of MYK-224 in Participants with Symptomatic Obstructive Hypertrophic Cardiomyopathy (MERCUTIO)
- Conditions
- Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular OutflowTract ObstructionTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]MedDRA version: 20.0Level: PTClassification code: 10020871Term: Hypertrophic cardiomyopathy Class: 100000004850
- Registration Number
- CTIS2023-508831-29-00
- Lead Sponsor
- Myokardia Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 29
PART A: 1) Has adequate acoustic windows, to enable accurate TTEs as determined by the echocardiography core laboratory., 2) 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. - Has a LVOT peak gradient during screening as assessed by echocardiography of = 50 millimeters of mercury (mm Hg) at rest, or = XML File Identifier: 4aHMkMObTnpietQCrlOf/erzF34= Page 18/33 30 mm Hg at rest and = 50 mm Hg after Valsalva maneuver (confirmed by echocardiography core laboratory interpretation)., 3) Has resting LVEF = 60% at the Screening visit as determined by echocardiography core laboratory., 4) Has a valid measurement of LVOT post-exercise peak gradient at screening as determined by echocardiography core laboratory. - NYHA functional class II or III symptoms at screening, 5) NYHA functional class II or III symptoms at screening, PART B: Participants that have successfully completed Part A of the study may enroll in Part B, an optional, 2-year open-label extension study. Eligibility for Part B will be assessed following completion of informed consent. Participants that have completed Part A EOS assessments within the Part B 28-day screening window may use those assessments for eligibility determination. Where possible, participants should enroll in Part B of the study on the same background therapy on which they completed Part A.
PART A: 1) Presence of any medical condition that precludes exercise stress testing., 10) Has known moderate or severe (per investigator's judgment) aortic valve stenosis at screening, 11) History of LV systolic dysfunction (LVEF < 45%) at any time during their clinical course, 12) Clinically significant pulmonary disease associated with exertional dyspnea, 13) Has known significant unrevascularized obstructive coronary artery disease (>70% stenosis in one or more main epicardial coronary XML File Identifier: 4aHMkMObTnpietQCrlOf/erzF34= Page 19/33 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., 14) 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 Sponsor Medical Monitor. Prior treatment with cardiotoxic agents such as anthracyclines (eg, doxorubicin) or similar, Part B: Medical conditions 1) Presence of any medical condition that precludes exercise stress testing, 2) Interval history of syncope or sustained ventricular tachyarrhythmia between the Part A EOS visit and the Part B Screening visit for participants that have a separate Screening visit for Part B, 3) Active infection, 4) Has been treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation [ASA]) following enrollment in Part A, 5) Has an interval history of resuscitated sudden cardiac arrest or of appropriate implantable cardioverter-defibrillator (ICD) discharge for life-threatening ventricular arrhythmia between Part A EOS visit and Screening for Part B, 2) History of syncope or sustained ventricular tachyarrhythmia within 6 months prior to screening., 6) Has paroxysmal, intermittent atrial fibrillation with atrial fibrillation present per the Investigator's evaluation of the subject's ECG at the time of Screening for Part B, 7) Has persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to Screening for Part B and/or not adequately rate controlled (Note: Participants with persistent or permanent atrial fibrillation who are anticoagulated and adequately rate-controlled are allowed. Please see restricted therapies in Appendix 5)., 8) Heart transplant or listed for heart transplant following enrollment in Part A, 9) Currently implanted LV assist device, 10) Clinically significant pulmonary disease associated with exertional dyspnea, 11) Has known significant unrevascularized obstructive coronary artery disease (> 70% stenosis in one or more epicardial coronary arteries) or history of myocardial infarction since enrollment in Part A, 3) Known infiltrative or storage disorder causing cardiac hypertrophy that mimics HCM, such as Fabry disease, amyloidosis, or Noonan syndrome with left ventricular hypertrophy., 4) 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)., 5) Implantable cardiove
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method