Phase II Study to Compare Anti-VEGF Agents in Treatment of DME (12-EI-0134)

比较抗 VEGF 药物治疗 DME 的 II 期研究 (12-EI-0134)

• 批准号: 8938355
• 负责人: Henry Wiley
• 金额: $ 7.76万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8938355
• 关键词: Adjuvant; Adverse event; Blindness; Cross-Over Studies; Diabetes Mellitus; Diabetic Retinopathy; Disease; Double-Blind Method; Enrollment; Extravasation; Eye; Fluorescein Angiography; Frequencies; Genetic Crossing Over; Injection of therapeutic agent; Left; Letters; Liquid substance; Masks; Measures; Outcome; Outcome Measure; Participant; Patients; Pattern; Pharmaceutical Preparations; Phase; Population Study; Randomized; Research Personnel; Resolution; Retinal; Safety; Secondary to; Series; Severities; Staging; Thick; Treatment Efficacy; Treatment Failure; Vascular Endothelial Growth Factors; Visit; Visual; Visual Acuity; Visual impairment; base; bevacizumab; comparative; design; diabetic; intravitreal injection; laser photocoagulation; macula; macular edema; meetings; phase 2 study; primary outcome; proliferative diabetic retinopathy; ranibizumab; secondary outcome; success

Objective: Diabetic retinopathy (DR) remains a leading cause of visual impairment. A frequent manifestation of DR is diabetic macular edema (DME) for which laser photocoagulation has been the only proven treatment for the last several decades. Studies have shown that anti-vascular endothelial growth factor (VEGF) injections such as bevacizumab or ranibizumab have been efficacious in treating patients with DME. However, there has been no direct comparison of these agents to determine whether one treatment is more effective than the other. The objective of this study is to compare the treatment efficacy of ranibizumab versus bevacizumab in eyes with DME. Study Population: Sixty (60) participants with macular edema secondary to diabetes and any stage of DR (other than those requiring scatter laser photocoagulation for proliferative DR) in one or both eyes will be enrolled in this randomized study. Design: In this Phase II, comparative, double-masked study, eyes will be randomly assigned to receive ranibizumab or bevacizumab. During the initial phase of the study participants will participate in a three-period, 36-week, cross-over study in which study eyes will be assigned to one of four treatment groups (i.e., treatment sequences). The two drugs and three periods form an AAB/ABB/BBA/BAA pattern as follows: Group 1 eyes will receive a series of intravitreal injections of ranibizumab at baseline and Weeks 4, 8, 12, 16 and 20, then cross-over to receive a series of intravitreal injections of bevacizumab at Weeks 24, 28 and 32. Group 2 eyes will receive a series of intravitreal injections of ranibizumab at baseline and Weeks 4 and 8, then cross-over to receive a series of intravitreal injections of bevacizumab at Weeks 12, 16, 20, 24, 28 and 32. Group 3 eyes will receive a series of intravitreal injections of bevacizumab at baseline and Weeks 4, 8, 12, 16 and 20, then cross-over to receive a series of intravitreal injections of ranibizumab at Weeks 24, 28 and 32. Group 4 eyes will receive a series of intravitreal injections of bevacizumab at baseline and Weeks 4 and 8, then cross-over to receive a series of intravitreal injections of ranibizumab at Weeks 12, 16, 20, 24, 28 and 32. Participants for whom one eye is enrolled in the study will have this eye randomized to one of the four groups above. Participants for whom both eyes are enrolled in the study will have the right eye randomized to one of the four groups above. For those whose right eye is randomized to Group 1 or 2, the left eye will be randomized to Group 3 or 4; conversely, for those whose right eye is randomized to Group 3 or 4, the left eye will be randomized to Group 1 or 2. Following this cross-over phase, eyes will be returned to the treatment (ranibizumab or bevacizumab) to which they were originally assigned and treated on an as-needed basis through a common termination date three years from enrollment of the last-enrolled participant. Both the treating investigators and participants will be masked to the group assignments. The primary outcome will be assessed at Weeks 12, 24, 36 and at Years 1, 2 and 3. Outcome Measures: The primary outcome measure is the mean change in best-corrected visual acuity (BCVA). Changes in BCVA from baseline to four weeks following the end of each of the three periods (i.e., Weeks 12, 24 and 36) and at Years 1, 2 and 3 will be used for the primary analysis. Secondary outcomes (assessed between the baseline and Week 12 visits, Weeks 12 and 24 visits and Weeks 24 and 36 visits and at Years 1, 2 and 3) will include the mean changes in central macular thickness and central retinal volume by treatment group as measured by OCT; the slope of the changes in BCVA, central macular thickness and retinal volume; the proportion of eyes with visual improvement greater than or equal to 10 letters; the proportion of eyes with visual improvement greater than or equal to 15 letters; the proportion of eyes with greater than or equal to 0.1 log unit loss or gain in logOCT; the proportion of eyes with greater than or equal to 0.05 log unit loss or gain in logOCT; changes in fluid leakage in the macula as demonstrated by fluorescein angiography; and changes in macular structural improvement (i.e., resolution of cystic changes) as measured by OCT. Other secondary outcomes will include the proportion of eyes meeting criteria for significant worsening, treatment success, or treatment failure, the frequency of re-injection among eyes in the treatment-as-needed phase of the study, and the proportion of eyes receiving focal/grid laser photocoagulation or other adjuvant treatment during the course of the study. Safety outcomes include the number and severity of adverse events. The number of eyes withdrawn from the investigational product due to vision loss or adverse events and the number of eyes deemed to have worsening disease will also contribute to the assessment of safety. Fifty-six (56) participants have been enrolled in the study and enrollment was closed in January 2014. All participants will complete the 36-week crossover phase of the trial by October 2014.

目的：糖尿病性视网膜病（DR）仍然是视觉障碍的主要原因。 DR的频繁表现是糖尿病性黄斑水肿（DME），在过去的几十年中，激光光凝是激光光凝是唯一可靠的治疗方法。研究表明，抗血管内皮生长因子（VEGF）注射（例如贝伐单抗或ranibizumab）在治疗DME患者方面有效。但是，没有直接比较这些药物来确定一种治疗是否比另一种治疗更有效。这项研究的目的是比较ranibizumab与DME眼睛中雷比珠单抗与贝伐单抗的治疗功效。研究人群：六十（60）个患有糖尿病继发的黄斑水肿和DR的任何阶段（除了需要激光散射激光凝集以进行增生DR的那些阶段）都将参与这项随机研究。设计：在此II阶段，比较，双掩盖研究中，将随机分配眼睛接受ranibizumab或贝伐单抗。在研究的初始阶段，参与者将参加三个周期的36周交叉研究，其中研究眼将分配给四个治疗组之一（即治疗序列）。这两种药物和三个时期形成了AAB/ABB/BBA/BAA模式：第1组的眼睛将在基线时在基线和第4、8、12、16和20周注射一系列玻璃纤维的玻璃体内注射，然后交叉，然后交叉接收一系列bevacizumab bevacizumab theext 24和32的bevacizumab的注射。 ranibizumab在基线和第4周和第8周，然后进行交叉，以在第12、16、20、20、24、28和32周注射一系列玻璃术的贝伐单抗。第3组的眼睛将接受一系列玻璃体内注射玻璃体玻璃体的注射，在基线和第4、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12、12和20 24、28和32。第4组眼睛将在基线和第4周和第8周收到一系列对贝伐单抗的玻璃体内注射，然后进行交叉，以接受一系列在第12、16、20、20、24、24、28和32周的玻璃尼替苏单抗注射玻璃纤维的玻璃体玻璃体内。在研究中，一只眼睛的参与者是一只眼睛的一部分。两只眼睛都参与研究的参与者将使右眼随机分配到上面的四组之一。对于那些被随机分配到第1组或第2组的人，左眼将被随机分为第3或4组；相反，对于那些右眼被随机分配到第3组或第4组的人，左眼将被随机分为第1组或第2组。在此交叉阶段，将把眼睛返回到治疗（Ranibizumab或bevacizumab），最初将其分配给他们，并在该治疗中分配并以所需的终止日期为基础，以在最终的终止日期内从最后的终止日期开始。治疗的调查人员和参与者都将被掩盖到小组分配中。主要结果将在第12、24、36周以及第1、2和3年度评估。结果指标：主要结果度量是最校正视力的平均变化（BCVA）。三个周期结束后的BCVA从基线到四个星期的变化（即第12、24和36周）以及在第1、2和3年的变化将用于主要分析。次要结果（在基线和第12周访问，第12周和第24周访问以及第24周和36次访问以及第1、2和3年的第12周评估）将包括中央黄斑厚度和中央视网膜体积的平均变化，如10月所测量； BCVA，中央黄斑厚度和视网膜体积的变化的斜率；视觉改善大于或等于10个字母的眼睛的比例；视觉改善大于或等于15个字母的眼睛的比例；徽标中大于或等于0.1对数单位损失或增益的眼睛比例；徽标中大于或等于0.05对数单位损失或增益的眼睛比例；如荧光素血管造影所证明的黄斑流体泄漏的变化；以及通过OCT测量的黄斑结构改善（即囊性变化的分辨率）的变化。其他次要结果将包括符合明显恶化，治疗成功或治疗失败标准的眼睛比例，研究阶段需要在治疗阶段重新注射的频率以及在研究过程中接受焦点/网格激光光凝或其他辅助治疗的眼睛的比例。安全结果包括不良事件的数量和严重性。由于视力丧失或不良事件，从研究产品中撤出的眼睛数量以及被认为恶化疾病的眼数也将有助于评估安全性。 该研究已入学56（56）名参与者，并于2014年1月关闭入学人数。所有参与者将在2014年10月之前完成试验的36周交叉阶段。