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 Contact: Name: First line of the email MUST contain NCT # and Site #.
• Study Contact Backup: Name: BMS Study Connect Contact Center http://www.bmsstudyconnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Local Institution - 0014
  • Wuerzburg, Germany, 97080
    • Local Institution - 0015
• 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	Time Frame
Frequency and severity of treatment-emergent adverse events and serious adverse events.	Up to 22 days, optional extension of up to 96 weeks
Number of participants with vital sign abnormalities	Up to 22 days, optional extension of up to 96 weeks
Number of participants with adverse event abnormalities	Up to 22 days, optional extension of up to 96 weeks
Number of participants with physical examination abnormalities	Up to 22 days, optional extension of up to 96 weeks
Number of participants with ECG abnormalities	Up to 22 days, optional extension of up to 96 weeks
Number of participants with safety lab abnormalities	Up to 22 days, optional extension of up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pharmacodynamic (PD) parameters assessed by transthoracic echocardiography (TTE)	Parameters include: Left ventricular systolic ejection time; Left ventricular stroke volume; Left ventricular ejection fraction; Left ventricular global longitudinal strain; Left ventricular global circumferential strain; Tissue Doppler imaging (TDI) of mitral valve annulus peak systolic velocity (s'); Left ventricular end systolic diameter; Left ventricular end diastolic diameter; Left ventricular end diastolic volume, indexed for body surface area (BSA); Left ventricular end systolic volume, indexed for BSA; Left atrial maximum volume, indexed for BSA; Left atrial minimum volume, indexed for BSA; Left atrial emptying fraction; Left atrial function index; TDI of mitral valve annulus peak velocity in diastole (e', lateral, septal); Ratio of peak inflow velocities in early and late diastole; Ratio of early mitral peak inflow velocity to early mitral peak annulus velocity (TDI) (E/e') lateral, septal, and average	Up to 96 weeks

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): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

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: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; 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