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

An Open-Label, Exploratory Study of the Safety and Preliminary Efficacy of Danicamtiv in Stable Ambulatory Participants With Primary Dilated Cardiomyopathy Due to Either MYH7 or TTN Variants or Other Causalities

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.

Study Overview

• Status: Terminated
• Conditions: Primary Familial Dilated Cardiomyopathy
• Intervention / Treatment: Drug: danicamtiv

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Wuerzburg, Germany, 97080
    • Local Institution - 0015
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Local Institution - 0014
• Spain
  • A Coruña, Spain, 15006
    • Local Institution - 0012
  • El Palmar, Spain, 30120
    • Local Institution - 0011
  • Majadahonda, Spain, 28222
    • Local Institution - 0013
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Local Institution - 0016
  • Middlesex, United Kingdom, UB9 6JH
    • Local Institution - 0017
• United States
  • California
    • La Jolla, California, United States, 92037
      • Local Institution - 0007
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Local Institution - 0010
  • Florida
    • Tampa, Florida, United States, 33612
      • Local Institution - 0009
  • Illinois
    • Chicago, Illinois, United States, 60611-5966
      • Local Institution - 0002
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Local Institution - 0003
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 0005
  • Ohio
    • Cleveland, Ohio, United States, 44195-0001
      • Local Institution - 0006
    • Columbus, Ohio, United States, 43210
      • Local Institution - 0019
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 0001
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Local Institution - 0004
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Local Institution - 0008
  • Texas
    • Austin, Texas, United States, 78705
      • Local Institution - 0018

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MYK-491; Primary DCM due to MYH7 or TTN Variant or due to other causalities not related to MYH7 or TTN variants	Drug: danicamtiv; Myosin activator; Other Names: MYK-491; BMS-986434

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) E/E Prime Average Ratio Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) E/E Prime Lateral Ratio Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) E/E Prime Septal Ratio Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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 Atrial Minimum Volume (LAminV) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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 Atrial Maximum Volume Index (LAmaxVi) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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 Atrial Emptying Fraction (LAEF) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.	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 Atrial Function Index (LAFI) Change From Baseline	Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days. Higher LAFI values are considered better left atrial function while lower LFAI values may indicate left atrial dysfunction.	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Actual): February 22, 2024
• Study Completion (Actual): February 22, 2024

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 29, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 5, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Primary dilated cardiomyopathy (DCM); Familial dilated cardiomyopathy (DCM); Myosin Heavy Chain 7 (MYH7); Titin (TTN); MYK-491; danicamtiv
• Additional Relevant MeSH Terms: Laminopathies; Cardiovascular Diseases; Heart Diseases; Genetic Diseases, Inborn; Cardiomegaly; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: CV028-005; 2019-003626-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No