A Multicenter, Randomized, Double-blind, Placebo-controlled Study of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome (vEDS) Confirmed With COL3A1 Mutations, Followed by an Open Label Extension (OLE)
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Time to intervention for an arterial event (rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm, fatal or not) or mortality attributable to an arterial event.
研究概览
简要总结
The purpose of this study is to investigate the efficacy of enzastaurin compared to placebo in preventing arterial events (rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm, fatal or not) leading to intervention or mortality attributable to an arterial event in patients with vEDS confirmed with pathogenic heterozygous COL3A1 gene mutations predicted to derive a mutant protein.
详细描述
The primary efficacy endpoint of this study will be defined as the time to intervention for an arterial event (rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm, fatal or not) or mortality attributable to an arterial event, as adjudicated by an Event Committee, and will be analyzed for difference of active vs. placebo treatments on top of background standard of care, using survival statistical analysis. Furthermore, secondary endpoints will include the rate of intestinal rupture, pneumothorax, and retinal detachment, as adjudicated by an Event Committee, safety and tolerability, as well as hospitalizations and Health Related Quality of Life (HQRL) measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects aged 18 - 60 years old at time of initial screening.
- •Adolescent subjects aged 12 - 17 years old, may be considered to enroll later in the clinical trial pending interim analysis.
- •Diagnosis for VEDS (vascular Ehlers Danlos Syndrome), with a confirmed and documented COL3A1 genetic variant.
- •Subject should be stable, having no VEDS-related vascular events within the past 3 months prior to enrollment.
- •Confirmed use of contraception for both male and female participants.
排除标准
- •Inability to swallow or receive intact tablets.
- •Currently being treated with CYP3A4 inhibitors within 4 weeks prior to enrollment.
- •Known allergy or hypersensitivity to enzastaurin.
- •Patient currently pregnant or breast feeding.
- •Other criteria will be reviewed at the first study visit to determine if you are able to participate in the study.
研究组 & 干预措施
Enzastaurin 500 mg QD
Receive 500 mg enzastaurin QD plus background standard of care.
干预措施: Enzastaurin (Drug)
Placebo QD
Matching placebo QD plus background standard of care.
干预措施: Placebo (Drug)
结局指标
主要结局
Time to intervention for an arterial event (rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm, fatal or not) or mortality attributable to an arterial event.
时间窗: 30 months
Time to intervention for an arterial event (rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm, fatal or not) or mortality attributable to an arterial event, as adjudicated by an Event Committee and analyzed for difference in the time-to-composite-event of active vs. placebo treatments, using survival analysis until end of study
次要结局
- Number of and proportion of patients with adverse events, or with abnormal vital signs, physical examinations, ophthalmological examinations, clinical laboratory values, or electrocardiograms (ECGs) medical attention.(30 months)
- Number of and proportion of patients who discontinue study drug due to adverse events(30 months)