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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Primary Familial Dilated Cardiomyopathy

Intervention / Treatment
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* Drug: danicamtiv


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary dilated cardiomyopathy (DCM), Familial dilated cardiomyopathy (DCM), Myosin Heavy Chain 7 (MYH7), Titin (TTN), MYK-491, danicamtiv