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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 41
- 试验地点
- 19
- 主要终点
- Number of Participants With Adverse Events (AEs) in Part A
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
MYK-491
Primary DCM due to MYH7 or TTN Variant or due to other causalities not related to MYH7 or TTN variants
干预措施: danicamtiv (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) in Part A
时间窗: From first dose to 30 days post last dose (Up to approximately 15 weeks)
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.
Number of Participants With Serious Adverse Events (SAEs) in Part A
时间窗: From first dose to 30 days post last dose (Up to approximately 15 weeks)
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.
Number of Participants With Safety Laboratory Assessments by Intensity in Part A
时间窗: From first dose to 14 days post last dose (Up to approximately 13 weeks)
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.
Number of Participants With Clinically Significant Changes in 12-Lead ECG Recordings in Part A
时间窗: 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.
Number of Participants With Clinically Significant Changes in Physical Examinations in Part A
时间窗: From first dose to 30 days post last dose (Up to approximately 15 weeks)
Number of participants with clinically significant changes in physical examinations.
Number of Participants With Clinically Significant Changes in Vital Signs in Part A
时间窗: From first dose to 30 days post last dose (Up to approximately 15 weeks)
Number of participants with clinically significant changes in vital signs.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Intensity in Part A
时间窗: From first dose to 14 days post last dose (Up to approximately 13 weeks)
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.)
次要结局
- 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)
- Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral 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) Tissue Doppler Imaging (TDI) S Prime Septal 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) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) 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) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) 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) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) 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) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) 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) Tissue Doppler Imaging (TDI) E Prime Lateral 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) Tissue Doppler Imaging (TDI) E Prime Septal 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) E/E Prime Average Ratio 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) E/E Prime Lateral Ratio 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) E/E Prime Septal Ratio 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) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A 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 Atrial Minimum Volume (LAminV) 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 Atrial Maximum Volume Index (LAmaxVi) 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 Atrial Emptying Fraction (LAEF) 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 Atrial Function Index (LAFI) 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)