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

NCT05556343 | Terminated Phase 2 FDA Drug

• 3 other identifiers: CV029-0092022-001292-14U1111-1276-3555
• Study Type: interventional
• Target: 18
• Locations: 4 countries
• Sites: 25

Brief 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)

Conditions

Cardiomyopathy, Hypertrophic

Keywords

Obstructive Hypertrophic Cardiomyopathy; MYK-224; BMS-986435; HCM

Outcome Measures

Primary Outcomes (8)

• Incidence of adverse events (AEs)

  Up to 53 weeks

• Incidence of arrhythmias

  Up to 53 weeks

• Incidence of appropriate implantable cardioverter defibrillator therapy and resuscitated cardiac arrest

  Up to 53 weeks

• Incidence of vital sign abnormalities

  Up to 53 weeks

• Incidence of physical examination abnormalities

  Up to 53 weeks

• Incidence of electrocardiogram (ECG) abnormalities

  Up to 53 weeks

• Incidence of transthoracic echocardiogram (TTE) abnormalities

  Up to 53 weeks

• Incidence of clinical laboratory abnormalities

  Up to 53 weeks

Secondary Outcomes (5)

• Change in left ventricular outflow tract (LVOT) peak gradient (post-exercise, resting, and Valsalva) from baseline to end of treatment

  Up to 45 weeks

• 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

• Concentration-response relationship between MYK-224 pharmacokinetics (PK) and LVOT peak gradients

  Up to 45 weeks

• Concentration-response relationship between MYK-224 PK and echocardiographic parameters of systolic and diastolic function

  Up to 45 weeks

• Summary of plasma concentrations of MYK-224

  Up to 53 weeks

Study Arms (2)

Cohort 1

EXPERIMENTAL

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

Drug: MYK-224

Cohort 2

EXPERIMENTAL

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

Drug: MYK-224

Interventions

MYK-224 DRUG

Specified dose on specified days

Also known as: BMS-986435

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (25)

Local Institution - 0026

La Jolla, California, 92037, United States

Location

Local Institution - 0014

Los Angeles, California, 90048, United States

Location

Local Institution - 0016

San Francisco, California, 94158-2156, United States

Location

Local Institution - 0001

Kansas City, Kansas, 66103-2937, United States

Location

Local Institution - 0032

New York, New York, 10032-3802, United States

Location

Local Institution - 0013

Durham, North Carolina, 27710, United States

Location

Local Institution - 0031

Cincinnati, Ohio, 45267, United States

Location

Local Institution - 0015

Cleveland, Ohio, 44195-0001, United States

Location

Local Institution - 0024

Portland, Oregon, 97239-3011, United States

Location

Local Institution - 0021

Nashville, Tennessee, 37205-2202, United States

Location

Local Institution - 0025

San Antonio, Texas, 78229-3900, United States

Location

Local Institution - 0006

Salt Lake City, Utah, 84132, United States

Location

Local Institution - 0027

Bologna, BO, 40138, Italy

Location

Local Institution - 0005

Florence, FI, 50134, Italy

Location

Local Institution - 0029

Milan, 20138, Italy

Location

Local Institution - 0011

Katowice, Silesian Voivodeship, 40-555, Poland

Location

Local Institution - 0030

Wroclaw, 54-049, Poland

Location

Local Institution - 0028

Alicante, A, 03010, Spain

Location

Local Institution - 0022

Granada, GR, 18014, Spain

Location

Local Institution - 0008

Málaga, MA, 29010, Spain

Location

Local Institution - 0002

El Palmar, MU, 30120, Spain

Location

Local Institution - 0003

Valencia, V, 46026, Spain

Location

Local Institution - 0009

A Coruña, 15006, Spain

Location

Local Institution - 0023

Barcelona, 08036, Spain

Location

Local Institution - 0010

Majadahonda, 28035, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2022
• First Posted: September 27, 2022
• Study Start: January 18, 2023
• Primary Completion: August 19, 2024
• Study Completion: February 27, 2025
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (12); IT (3); PL (2); ES (8)