Clinical trial NCT04572893: Exploratory Study of Danicamtiv in Patients With Primary Dilated Cardiomyopathy (DCM) Due to Genetic Variants or Other Causalities
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Familial Dilated Cardiomyopathy
Keywords: Primary dilated cardiomyopathy (DCM)
Familial dilated cardiomyopathy (DCM)
Myosin Heavy Chain 7 (MYH7)
Titin (TTN)
MYK-491
danicamtiv
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2020-10-01
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) in Part A
timeFrame: From first dose to 30 days post last dose (Up to approximately 15 weeks)
measure: Number of Participants With Serious Adverse Events (SAEs) in Part A
timeFrame: From first dose to 30 days post last dose (Up to approximately 15 weeks)
measure: Number of Participants With Safety Laboratory Assessments by Intensity in Part A
timeFrame: From first dose to 14 days post last dose (Up to approximately 13 weeks)
measure: Number of Participants With Clinically Significant Changes in Physical Examinations in Part A
timeFrame: From first dose to 30 days post last dose (Up to approximately 15 weeks)
measure: Number of Participants With Clinically Significant Changes in Vital Signs in Part A
timeFrame: From first dose to 30 days post last dose (Up to approximately 15 weeks)
measure: Number of Participants With Clinically Significant Changes in 12-Lead ECG Recordings in Part A
timeFrame: From first dose to 30 days post last dose (Up to approximately 15 weeks)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Intensity in Part A
timeFrame: From first dose to 14 days post last dose (Up to approximately 13 weeks)
Secondary outcomes:
measure: Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline
timeFrame: 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
measure: Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline
timeFrame: 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
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Local Institution - 0007
state: California
city: Washington
country: United States
facility: Local Institution - 0010
state: District of Columbia
city: Tampa
country: United States
facility: Local Institution - 0009
state: Florida
city: Chicago
country: United States
facility: Local Institution - 0002
state: Illinois
city: Boston
country: United States
facility: Local Institution - 0003
state: Massachusetts
city: Rochester
country: United States
facility: Local Institution - 0005
state: Minnesota
city: Cleveland
country: United States
facility: Local Institution - 0006
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0019
state: Ohio
city: Philadelphia
country: United States
facility: Local Institution - 0001
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0004
state: South Carolina
city: Germantown
country: United States
facility: Local Institution - 0008
state: Tennessee
city: Austin
country: United States
facility: Local Institution - 0018
state: Texas
city: Heidelberg
country: Germany
facility: Local Institution - 0014
state: Baden-Württemberg
city: Wuerzburg
country: Germany
facility: Local Institution - 0015
city: A Coruña
country: Spain
facility: Local Institution - 0012
city: El Palmar
country: Spain
facility: Local Institution - 0011
city: Majadahonda
country: Spain
facility: Local Institution - 0013
city: London
country: United Kingdom
facility: Local Institution - 0016
city: Middlesex
country: United Kingdom
facility: Local Institution - 0017
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: