Exploratory Study of Danicamtiv in Patients With Primary Dilated Cardiomyopathy (DCM) Due to Genetic Variants or Other Causalities

NCT04572893 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CV028-0052019-003626-24
• Study Type: interventional
• Target: 41
• Locations: 4 countries
• Sites: 19

Brief Summary

The purpose of this Phase 2a study is to establish safety and preliminary efficacy of treatment with danicamtiv in patients with primary dilated cardiomyopathy (DCM) due to MYH7 or TTN variants or other causalities.

Conditions

Primary Familial Dilated Cardiomyopathy

Keywords

Primary dilated cardiomyopathy (DCM); Familial dilated cardiomyopathy (DCM); Myosin Heavy Chain 7 (MYH7); Titin (TTN); MYK-491; danicamtiv

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Adverse Events (AEs) in Part A

  An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.

  From first dose to 30 days post last dose (Up to approximately 15 weeks)

• Number of Participants With Serious Adverse Events (SAEs) in Part A

  An 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, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event.

  From first dose to 30 days post last dose (Up to approximately 15 weeks)

• Number of Participants With Safety Laboratory Assessments by Intensity in Part A

  Number of participants with safety laboratory assessments by intensity. Mild=An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate= An event causing sufficient discomfort and interferes with normal everyday activities.

  From first dose to 14 days post last dose (Up to approximately 13 weeks)

• Number of Participants With Clinically Significant Changes in Physical Examinations in Part A

  Number of participants with clinically significant changes in physical examinations.

  From first dose to 30 days post last dose (Up to approximately 15 weeks)

• Number of Participants With Clinically Significant Changes in Vital Signs in Part A

  Number of participants with clinically significant changes in vital signs.

  From first dose to 30 days post last dose (Up to approximately 15 weeks)

• Number of Participants With Clinically Significant Changes in 12-Lead ECG Recordings in Part A

  Number of participants with clinically significant changes in 12-lead ECG recordings.

  From first dose to 30 days post last dose (Up to approximately 15 weeks)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Intensity in Part A

  An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Mild=An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate= An event causing sufficient discomfort and interferes with normal everyday activities. Severe= An event preventing normal everyday activities. (An AE that is assessed as severe should not be confused with a SAE. Severe is a category utilized for rating the intensity of an event; and both AEs and SAEs can be assessed as severe.)

  From first dose to 14 days post last dose (Up to approximately 13 weeks)

Secondary Outcomes (21)

• Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline

  Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

• Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline

  Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

• Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline

  Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 42, 48, and early termination

• Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline

  Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 42, 48, and early termination

• Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline

  Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 42, 48, and early termination

Study Arms (1)

MYK-491

EXPERIMENTAL

Primary DCM due to MYH7 or TTN Variant or due to other causalities not related to MYH7 or TTN variants

Drug: danicamtiv

Interventions

danicamtiv DRUG

Myosin activator

Also known as: MYK-491, BMS-986434

MYK-491

Eligibility Criteria

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

You may qualify if:

• For MYH7 and TTN cohorts, must have diagnosis of primary DCM (dilated cardiomyopathy), clinically stable and due to probably disease-causing variant of MYH7 or TTN
• Has adequate acoustic windows for echocardiography
• Maximum of 3 family members with same variant can be enrolled
• For the cohort of primary DCM due to causalities other than MYH7 and TTN, participant must have diagnosis of primary DCM with a cause not related to MYH7 or TTN variants

You may not qualify if:

• Significant structural cardiac abnormalities including valvar dysfunction on Screening transthoracic echo(s)
• Routinely scheduled outpatient intravenous (IV) infusions for heart failure (e.g., inotropes, afterload reduction, or diuretics)
• Presence of protocol specified laboratory abnormalities at Screening
• Recent acute coronary syndrome or angina pectoris (\<90 days)
• Recent hospitalization for heart failure (\<90 days)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (19)

Local Institution - 0007

La Jolla, California, 92037, United States

Location

Local Institution - 0010

Washington D.C., District of Columbia, 20007, United States

Location

Local Institution - 0009

Tampa, Florida, 33612, United States

Location

Local Institution - 0002

Chicago, Illinois, 60611-5966, United States

Location

Local Institution - 0003

Boston, Massachusetts, 02115, United States

Location

Local Institution - 0005

Rochester, Minnesota, 55905, United States

Location

Local Institution - 0006

Cleveland, Ohio, 44195-0001, United States

Location

Local Institution - 0019

Columbus, Ohio, 43210, United States

Location

Local Institution - 0001

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 0004

Charleston, South Carolina, 29425, United States

Location

Local Institution - 0008

Germantown, Tennessee, 38138, United States

Location

Local Institution - 0018

Austin, Texas, 78705, United States

Location

Local Institution - 0014

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Local Institution - 0015

Würzburg, 97080, Germany

Location

Local Institution - 0012

A Coruña, 15006, Spain

Location

Local Institution - 0011

El Palmar, 30120, Spain

Location

Local Institution - 0013

Majadahonda, 28222, Spain

Location

Local Institution - 0016

London, EC1A 7BE, United Kingdom

Location

Local Institution - 0017

Middlesex, UB9 6JH, United Kingdom

Location

Related Publications (1)

• Lakdawala NK, Hershberger RE, Garcia-Pavia P, Elliott PM, Ginns J, Meder B, Solomon S, Cunningham JW, Gimeno JR, Barriales-Villa R, Adler E, Gerull B, Pereira NL, Halliday BP, Li W, Jarugula P, Maruyama S, Mohran SE, Papadaki M, Anto AR, Anderson RL, Rodriguez HM, Del Rio CL, Edelberg JM, Kurio G, Maya J, Januzzi JL. Danicamtiv, a Selective Agonist of Cardiac Myosin, for Dilated Cardiomyopathy: A Phase 2 Open-Label Trial. J Am Coll Cardiol. 2025 Dec 23;86(25):2598-2612. doi: 10.1016/j.jacc.2025.09.1511. Epub 2025 Sep 29.

  PMID: 41217321 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Campomelic Dysplasia; Cardiomyopathy, Dilated; familial dilated cardiomyopathy; Distal Myopathies; Hereditary Sensory and Autonomic Neuropathies

Condition Hierarchy (Ancestors)

Musculoskeletal Abnormalities; Musculoskeletal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: October 1, 2020
• Study Start: August 4, 2020
• Primary Completion: February 22, 2024
• Study Completion: February 22, 2024
• Last Updated: May 21, 2025
• Results First Posted: May 21, 2025

Record last verified: 2025-05

Locations

DE (2); GB (2); US (12); ES (3)