BridgeMD
Multiple Dose Study to Evaluate Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of MYK-224 in Participants with Symptomatic Obstructive Hypertrophic Cardiomyopathy (MERCUTIO)
EU CTIS ID: 2023-508831-29-00
What this study is testing
To assess the safety and tolerability of MYK-224 in participants with symptomatic oHCM (Part A)
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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.
You likely can't join if
- 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
See the full eligibility criteria
Who can join
- 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.
What rules you out
- 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 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)
- 6) 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
- 7) Has paroxysmal, atrial fibrillation with atrial fibrillation present per the Investigator's evaluation of the subject's ECG at the time of Screening
- 8) 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
- 9) 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)
The study team makes the final eligibility decision.
Where it's taking place
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.