A Study to Evaluate the Efficacy, Safety, and Tolerability of MYK-224 in Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Cardiomyopathy, Hypertrophic Clinical Trial

— MERCUTIO  

Official title:

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 (MERCUTIO)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05556343
• Other study ID #: CV029-009
• Secondary ID: 2022-001292-14U1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 18, 2023
• Est. completion date: October 2, 2026

Study information

• Verified date: June 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: October 2, 2026
• Est. primary completion date: July 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophy

Intervention

Drug:
• MYK-224
Specified dose on specified days

Locations

Country	Name	City	State
Italy	Local Institution - 0027	Bologna	BO
Italy	Local Institution - 0005	Firenze	FI
Italy	Local Institution - 0029	Milano
Poland	Local Institution - 0011	Katowice	SL
Poland	Local Institution - 0030	Wroclaw
Spain	Local Institution - 0009	A Coruña
Spain	Local Institution - 0028	Alicante	A
Spain	Local Institution - 0023	Barcelona
Spain	Local Institution - 0002	El Palmar	MU
Spain	Local Institution - 0022	Granada	GR
Spain	Local Institution - 0010	Majadahonda
Spain	Local Institution - 0008	Málaga	MA
Spain	Local Institution - 0003	Valencia	V
United States	Local Institution - 0031	Cincinnati	Ohio
United States	Local Institution - 0015	Cleveland	Ohio
United States	Local Institution - 0013	Durham	North Carolina
United States	Local Institution - 0001	Kansas City	Kansas
United States	Local Institution - 0026	La Jolla	California
United States	Local Institution - 0014	Los Angeles	California
United States	Local Institution - 0021	Nashville	Tennessee
United States	Local Institution - 0032	New York	New York
United States	Local Institution - 0024	Portland	Oregon
United States	Local Institution - 0006	Salt Lake City	Utah
United States	Local Institution - 0025	San Antonio	Texas
United States	Local Institution - 0016	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AEs)		Up to 53 weeks
Primary	Incidence of arrhythmias		Up to 53 weeks
Primary	Incidence of appropriate implantable cardioverter defibrillator therapy and resuscitated cardiac arrest		Up to 53 weeks
Primary	Incidence of vital sign abnormalities		Up to 53 weeks
Primary	Incidence of physical examination abnormalities		Up to 53 weeks
Primary	Incidence of electrocardiogram (ECG) abnormalities		Up to 53 weeks
Primary	Incidence of transthoracic echocardiogram (TTE) abnormalities		Up to 53 weeks
Primary	Incidence of clinical laboratory abnormalities		Up to 53 weeks
Secondary	Change in left ventricular outflow tract (LVOT) peak gradient (post-exercise, resting, and Valsalva) from baseline to end of treatment		Up to 45 weeks
Secondary	Proportion of participants achieving a resting LVOT peak gradient of < 30 mm Hg and a Valsalva LVOT peak gradient < 50 mm Hg at end of treatment		Up to 45 weeks
Secondary	Concentration-response relationship between MYK-224 pharmacokinetics (PK) and LVOT peak gradients		Up to 45 weeks
Secondary	Concentration-response relationship between MYK-224 PK and echocardiographic parameters of systolic and diastolic function		Up to 45 weeks
Secondary	Summary of plasma concentrations of MYK-224		Up to 53 weeks

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting