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

NCT05556343 | Terminated Phase 2 Results 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 (14)

• Part A: Number of Participants With Adverse Events and Serious Adverse Events

  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization.

  From first dose (Day 1) until study end date in Part A or 30 days after early termination date (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Number of Participants With at Least One Event of Arrhythmias

  Arrhythmias included atrial fibrillation/flutter (new from screening and recurrent), ventricular tachyarrhythmias (ventricular tachycardia, ventricular fibrillation, and Torsades de Pointe).

  From first dose (Day 1) until study end date in Part A or 30 days after early termination date (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Number of Participants With at Least One Event of Appropriate Implantable Cardioverter Defibrillator Therapy and Resuscitated Cardiac Arrest

  From first dose (Day 1) until study end date in Part A or 30 days after early termination date (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Change From Baseline in Vital Signs - Heart Rate

  Baseline is defined as the last non-missing value in date/time recorded before the first dose of MYK-224. Heart rate was measured in rested state.

  Baseline and until treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Change From Baseline in Vital Signs - Mean Systolic Blood Pressure

  Baseline is defined as the last non-missing value in date/time recorded before the first dose of MYK-224. Systolic blood pressure was measured in rested state.

  Baseline and until treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Change From Baseline in Vital Signs - Mean Diastolic Blood Pressure

  Baseline is defined as the last non-missing value in date/time recorded before the first dose of MYK-224. Diastolic blood pressure was measured in rested state.

  Baseline and until treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Change From Baseline in Vital Signs - Respiratory Rate

  Baseline is defined as the last non-missing value in date/time recorded before the first dose of MYK-224. Respiratory rate was measured in rested state.

  Baseline and until treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Change From Baseline in Vital Signs - Temperature

  Baseline is defined as the last non-missing value in date/time recorded before the first dose of MYK-224.

  Baseline and until treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Change From Baseline in Vital Signs - Weight

  Baseline is defined as the last non-missing value in date/time recorded before the first dose of MYK-224.

  Baseline and until treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Number of Participants With Abnormal Physical Examination Results

  The complete physical examination included weight and calculated BMI, a neurological examination (gross motor and deep tendon reflexes),and an assessment of the following: general appearance, skin, head and neck, mouth, lymph nodes, thyroid, abdomen, musculoskeletal, cardiovascular, neurological, and respiratory systems with other systems included, as directed by interval history.

  Baseline and until study end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Results

  Twelve-lead ECG evaluations will be performed in the supine position after 10 minutes of rest at Screening and at selected clinic visits prior to MYK-224 dosing and before any blood sample collection. QTc prolongation is defined by either the mean of QTcF \> 499 or mean of QTcB \> 499 according to the project requirement specification from Clario.

  Baseline and until study end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Number of Participants With Adverse Events Related to Clinical Laboratory Parameters (Hematology, Chemistry and Urinalysis)

  Blood samples were collected to assess the clinical laboratory parameters.

  Baseline and untill end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A:Percentage of Participants With Incidence of Symptomatic Left Ventricular Ejection Fraction (LVEF) < 50%

  LVEF was assessed using transthoracic echocardiogram (TTE) in resting state. 90% CIs are calculated based on Exact Binomial proportion test. LVEF value was calculated by Simpson Biplane method.

  From first dose (Day 1) until study end date in Part A or 30 days after early termination date (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Percentage of Participants With Incidence of Symptomatic Left Ventricular Ejection Fraction (LVEF) <= 30%

  LVEF was assessed using transthoracic echocardiogram (TTE) in resting state. 90% CIs are calculated based on Exact Binomial proportion test. LVEF value was calculated by Simpson Biplane method.

  From first dose (Day 1) until study end date in Part A or 30 days after early termination date (Median 17.55 weeks and Maximum 54.9 weeks)

Secondary Outcomes (6)

• Part A: Aggregate Mean of Left Ventricular Ejection Fraction (LVEF)

  Treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

  Baseline and until treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Aggregate Mean of Left Ventricular Outflow Tract (LVOT) Peak Gradient (Post-Exercise, Resting, and Valsalva)

  Treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Change From Baseline in Left Ventricular Outflow Tract (LVOT) Peak Gradient (Post-Exercise, Resting, and Valsalva)

  Treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 weeks)

• Part A: Percentage of Participants With Resting Left Ventricular Outflow Tract (LVOT) Peak Gradient < 30 mmHg and Valsalva LVOT Peak Gradient < 50 mmHg

  Baseline and until treatment end date in Part A (Median 17.55 weeks and Maximum 54.9 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

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: June 2, 2026
• Results First Posted: June 2, 2026

Record last verified: 2026-06

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)