A Phase III, Randomized, Controlled, Open Label, Multicenter Study of the Efficacy and Safety of Trinam® (EG004); an Assessment of Primary Unassisted Patency and Survival of Vascular Access Grafts in Hemodialysis Patients With End Stage Renal Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 250
- 试验地点
- 22
- 主要终点
- Primary Unassisted Patency
研究概览
简要总结
Patients in renal failure on hemodialysis depend on adequate and sustained vascular access. This can be achieved by surgical placement of a synthetic polytetrafluoroethylene (PTFE) graft. These patients frequently experience graft complications arising from the development of smooth muscle cell (SMC) neointimal hyperplasia in the proximity of the graft-vein anastomosis. Such complications eventually lead to stenosis, access thrombosis and graft failure. Trinam® is being developed to prolong graft survival. It is a combination product consisting of a replication deficient Adenovirus containing the human Vascular Endothelial Growth Factor D (Ad-VEGF-D) gene and a biodegradable local delivery device (collar) made of collagen. At the end of the surgical procedure to insert the PTFE graft the collagen collar is applied around the anastomosis and sealed with a collagen surgical sealant. This procedure creates a reservoir between the site of anastomosis and the collagen collar. The adenoviral vector is then injected into this reservoir, localizing the expression of the transgene to the site of the anastomosis. Expression of VEGF-D has been shown to have a vascular protective role and inhibit SMC neointimal proliferation, therefore expression of VEGF-D should prolong graft survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with end stage renal disease undergoing either initial placement or replacement (after failure of previous vascular access) of an end-to-side or end-to-end 6.0 mm synthetic PTFE arteriovenous hemodialysis access arm graft.
- •Male or female aged 18 years or over.
- •Patients who signed the informed consent form.
- •Patients who are expected to undergo dialysis at nominated facilities for the duration of the study.
- •Patients who have agreed to participate in the additional four year gene therapy safety monitoring.
- •Patients who are willing to agree they will not have a kidney transplant for four weeks post treatment with Trinam®.
- •Patients who have undergone arterial and venous mapping to ensure an adequate and appropriate access site is available for placement of either an end-to-side or an end-to-end 6.0 mm synthetic PTFE arteriovenous hemodialysis access arm graft with or without the addition of Trinam®.
排除标准
- •Patients who are unable to understand and sign the consent form.
- •Patients undergoing surgical revision of an existing graft.
- •Exclude patients from the study if they have moderate or severe macular edema moderate or severe proliferative diabetic retinopathy
- •Current diagnosis of cancer with exception of non-melanoma skin cancers.
- •Hepatic dysfunction defined as AST and / or ALT > 2 times the Upper Limit of Normal.
- •Diabetic patients with Hemoglobin A1C value of >10%.
- •White blood cell (WBC) count < 2.0 x 109/L.
- •Prior anticoagulant therapy within 14 days prior to surgery is an exclusion.
- •Known sensitivity to collagen.
- •Pregnancy, lactation or lack of effective contraception both in women and in men of childbearing potential.
- •Previous participation in any Trinam® study.
- •Receipt of any investigational drug within 30 days prior to study enrollment or participation in any concurrently running trial involving investigational intervention.
- •Any medical or psychiatric condition that compromises the ability to participate in the study.
- •Known or suspected drug or alcohol abuse in the past six months.
- •Life expectancy of less than one year.
- •Known immunodeficiency disease.
- •Known chronic hepatitis of viral or non-viral etiology and / or a history of decompensated liver failure of any etiology.
结局指标
主要结局
Primary Unassisted Patency
时间窗: 18 Months
次要结局
- Graft Survival. Number and rate of graft interventions.(2.5 years)