The Safety and Tolerability of Intravitreal Adalimumab in Patients With Refractory Diabetic Macular Retinopathy or Choroidal Neovascularization or Uveitis: A Pilot Study
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- The main outcome measure will be visual acuity improvement (3 lines)
研究概览
简要总结
Direct intravitreal administration of medication is the preferred method of treatment for uveitis and retinal vascular disorders. The eye is a self contained organ relatively isolated from the systemic circulation by the tight blood retinal barrier. Effective intraocular drug levels can be achieved with a much smaller amount of medication if injected intravitreally and this also results in minimal systemic exposure to the patient. Preliminary studies have shown that adalimumab may have a positive role in the management of uveitis in humans and can be an effective treatment intravitreally in animal models. No data has been published yet on intravitreal use of adalimumab in human subjects.
详细描述
Abstract Purpose: Our aim is study to determine the efficacy and safety of intravitreal adalimumab in patients with active vision threatening uveitis, diabetic macular edema (DME) and choroidal neovascularization (CNV) despite standard treatment and to ensure its safety in intravitreal use in humans and its rapid onset of action.
Design: Pilot study, Non-Randomized, Open Label, Single Group Assignment, Safety Study.
Participants: 15 eyes with refractory CNV, DME, or uveitis will be injected with intravitreal adalimumab on a 3 week interval. Patients will satisfy the inclusion and exclusion criteria listed at the end.
Methods: Initial treatment will consist of intravitreal adalimumab injection (1.5 mg/ 0.03 mL) in the eyes of patients with refractory CNV, DME, or uveitis and with visual acuity less than or equal to 20/70. Patients will be followed up every 3 weeks for a total of 6 weeks. Patients will have a baseline best-corrected visual acuity (BCVA), slit lamp examination, dilated fundus examination, ocular coherence tomography (OCT), fluorescein angiography (F.A), and standard electroretinogram (ERG) and then these studies will be repeated every visit. If there is stabilization or improvement in visual acuity, decrease in edema on OCT and leakage on F.A after the first injection, then further injections will be given. The injection will be delayed if a patient develops an acute systemic infection and will be given when it subsides. If there is worsening of visual acuity after the first injection, patients will be shifted to the traditional treatment with intravitreal Avastin or intravitreal steroids. The paired sample Student t- test, Chi-square test, Pearson correlation and ANOVA will be used to analyze the mean visual acuity and central retinal thickness before and after treatment.
Main outcome measures: to study the response to intravitreal adalimumab injection of patients with different visual acuity at baseline measured in terms of improvement in visual acuity, shrinkage in central retinal thickness, reduction in fluid leakage, and decrease in the active inflammatory uveitis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 17 Years 至 88 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provide written informed consent and comply with study assessments for the full duration of the study
- •Age > 17 years
- •Patients with active choroidal neovascularization, diabetic retinopathy, or uveitis in the study eye which did not improve with conventional therapy
- •Best corrected visual acuity of 20/70 or less.
排除标准
- •Are participating in another clinical study requiring follow up examinations
- •Have received any other experimental drug within 12 weeks prior to enrollment
- •Are unwilling or unable to follow or comply with all study-related procedures
- •Inability to obtain photographs, fluorescein angiography, or optical coherence tomography to document CNV, e.g. due to media opacity, allergy to fluorescein dye or lack of venous access
- •Aphakia or pseudophakia with the absence of posterior capsule (unless it resulted from a yttrium aluminum garner [YAG]) posterior capsulotomy)
- •Within two months prior to screening, have had intraocular surgery (including cataract surgery) in the study eye
- •Within 1 month prior to screening had YAG laser in the study eye
- •Have had intravitreal anti VEGF or intravitreal steroids in the last 6 weeks
- •Have had previous pars plana vitrectomy in the study eye
- •Are pregnant or are trying to become pregnant
- •Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
研究组 & 干预措施
adalimumab arm
intravitreal mode of delivery
干预措施: adalimumab (Drug)
结局指标
主要结局
The main outcome measure will be visual acuity improvement (3 lines)
时间窗: 6 weeks
次要结局
- central foveal thickness and angiographic lesion size(6 weeks)