A Phase 3 Multicenter, Randomized, Sham-Controlled Study to Determine the Safety and Efficacy of Renexus in Macular Telangiectasia Type 2

目的：确定Renexus（一种分泌睫状神经营养因子（CNTF）的眼内包封细胞植入物）治疗2型黄斑毛细血管扩张症（MacTel）的疗效和安全性。 研究人群：本研究对所有符合入选/排除标准的确诊MacTel 2型患者开放。 在这项多中心研究中，所有研究中心约112例受试者将接受研究干预。 NEI研究中心将筛选最多12名受试者，目标是为最多6名受试者提供研究干预。 设计：这是一项III期、多中心、单盲、假对照研究， 大约有112名研究参与者患有MacTel 2型。每位参与者将 贡献一只研究眼。受试者将随机（1：1）接受Renexus 植入手术或假手术。所有参与者将接受24个月的随访。 所有受试者将有长达30天的筛选期，手术/假手术将在完成筛选后4周内进行。 研究眼将在第0天接受Renexus植入手术或假手术，并将在第1天、第1周（2天）、第6个月（4周）、第12个月（4周）、第16个月（4周）、第20个月（4周）和第24个月（4周）进行评估。将在第1个月（1周）和第3个月（1周）进行电话联系。 结局指标： 主要结局：主要结局将是通过SD-OCT对研究眼进行正面成像测量的椭圆体区破坏面积（光感受器内段/外段信号丢失面积）从基线至24个月的平均变化。 次要结局：研究疗效的次要结局包括以下内容，比较接受Renexus的受试者与接受假干预的受试者： 通过SD-OCT测量的中心黄斑厚度从基线至24个月的平均变化。 24个月时椭圆体区破坏面积较基线增加> 35%的眼睛比例。 从基线至24个月，椭圆区破坏区域内微视野检查的总体灵敏度的平均变化。 24个月内阅读速度较基线的平均变化。 NEI视功能问卷近距离活动子量表评分从基线至24个月的平均变化。 研究安全性的次要结局包括： 视力持续恶化的参与者数量，包括使用ETDRS测试丢失> 15个字母。 2018年，我们被激活为III期临床试验（18-EI-0055）的研究中心。 我们已招募五名参与者，并于二零二零财政年度继续跟进。

Objective: To determine the efficacy and safety of Renexus, an intraocular encapsulated cell implant secreting ciliary neurotrophic factor (CNTF), for the treatment of macular telangiectasia (MacTel) type 2. Study Population: This study is open to all persons with confirmed MacTel Type 2 who meet the Inclusion/Exclusion Criteria. Approximately 112 participants across all sites in this multicenter study will undergo study intervention. The NEI site will screen up to 12 participants, with a goal of offering study intervention to up to 6 participants. Design: This is a phase III, multi-center, single-masked, sham-controlled study of approximately 112 study participants with MacTel Type 2. Each participant will contribute a single study eye. Participants will be randomized (1:1) to receive the Renexus implant surgery or sham surgery in the study-eligible eye. All participants will be followed through 24 months. All participants will have a screening period of up to 30 days, and surgery/sham will occur within 4 weeks after completing screening. Study eyes will receive the Renexus implant surgery or sham surgery on Day 0 and will be assessed on Day 1, Week 1 ( 2 days), Month 6 ( 4weeks), Month 12 (4 weeks), Month 16 ( 4 weeks), Month 20 ( 4 weeks) and Month 24 ( 4 weeks). A telephone contact will be made at Month 1 ( 1 week), and Month 3 ( 1 week). Outcome Measures: Primary Outcome: The primary outcome will be the mean change in the area of ellipsoid zone disruption (area of photoreceptor inner segment/outer segment signal loss) from baseline through 24 months as measured by en face imaging by SD-OCT in the study eye. Secondary Outcomes: Secondary outcomes to investigate efficacy include the following, comparing participants receiving Renexus with those receiving sham intervention: Mean change in central macular thickness as measured by SD-OCT from baseline through 24 months. Proportion of eyes with > 35% increase in the area of ellipsoid zone disruption from baseline at 24 months. Mean change in aggregate sensitivity of microperimetry within the area of ellipsoid zone disruption from baseline through 24 months. Mean change in reading speed from baseline through 24 months. Mean change in the NEI Visual Function Questionnaire near activities subscale score from baseline through 24 months. Secondary outcomes to investigate safety include the following: Number of participants with persistent deterioration in visual acuity, consisting of loss of >15 letters using ETDRS testing. In 2018, we were activated as a site in the phase 3 clinical trial (18-EI-0055). We have enrolled five participants, and follow up has continued during fiscal year 2020.