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

NCT ID: NCT05556343

Last Updated: 2025-08-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-18

Study Completion Date

2025-02-27

Brief Summary

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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)

Detailed Description

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Conditions

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Cardiomyopathy, Hypertrophic

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

MYK-224

Intervention Type DRUG

Specified dose on specified days

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

Group Type EXPERIMENTAL

MYK-224

Intervention Type DRUG

Specified dose on specified days

Interventions

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MYK-224

Specified dose on specified days

Intervention Type DRUG

Other Intervention Names

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BMS-986435

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0026

La Jolla, California, United States

Site Status

Local Institution - 0014

Los Angeles, California, United States

Site Status

Local Institution - 0016

San Francisco, California, United States

Site Status

Local Institution - 0001

Kansas City, Kansas, United States

Site Status

Local Institution - 0032

New York, New York, United States

Site Status

Local Institution - 0013

Durham, North Carolina, United States

Site Status

Local Institution - 0031

Cincinnati, Ohio, United States

Site Status

Local Institution - 0015

Cleveland, Ohio, United States

Site Status

Local Institution - 0024

Portland, Oregon, United States

Site Status

Local Institution - 0021

Nashville, Tennessee, United States

Site Status

Local Institution - 0025

San Antonio, Texas, United States

Site Status

Local Institution - 0006

Salt Lake City, Utah, United States

Site Status

Local Institution - 0027

Bologna, BO, Italy

Site Status

Local Institution - 0005

Florence, FI, Italy

Site Status

Local Institution - 0029

Milan, , Italy

Site Status

Local Institution - 0011

Katowice, Silesian Voivodeship, Poland

Site Status

Local Institution - 0030

Wroclaw, , Poland

Site Status

Local Institution - 0028

Alicante, A, Spain

Site Status

Local Institution - 0022

Granada, GR, Spain

Site Status

Local Institution - 0008

Málaga, MA, Spain

Site Status

Local Institution - 0002

El Palmar, MU, Spain

Site Status

Local Institution - 0003

Valencia, V, Spain

Site Status

Local Institution - 0009

A Coruña, , Spain

Site Status

Local Institution - 0023

Barcelona, , Spain

Site Status

Local Institution - 0010

Majadahonda, , Spain

Site Status

Countries

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United States Italy Poland Spain

Related Links

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Other Identifiers

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2022-001292-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1276-3555

Identifier Type: REGISTRY

Identifier Source: secondary_id

CV029-009

Identifier Type: -

Identifier Source: org_study_id

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