A Phase 2 Multicenter Randomized Clinical Trial of Ciliary Neurotrophic Factor (CNTF) for Macular Telangiectasia Type 2 (MacTel) (14-EI-0078)

目的：研究分泌睫状神经营养因子(CNTF)的NT-501装置对24月龄黄斑毛细血管扩张症(Mactel)患者黄斑椭圆区破裂面积变化的影响。方法：采用光谱域光学相干断层扫描(SD-OCT)对黄斑椭圆形带裂伤患者进行面部成像。 研究人群：68(68)名患有MACTEL 2型的参与者将被纳入研究范围。NEI将招收最多10名参与者。初步分析将包括五名参与者；最多可以再招募五名参与者，以说明不符合资格标准的参与者。符合条件的参与者将是21至80岁的成年人，在筛查访问时，他们至少有一只研究眼有2型黄斑变性的阳性诊断，有典型的黄斑变性的荧光素渗漏证据，或至少一种其他特征，包括视网膜混浊、晶体沉积、直角血管、内/外板层空洞或不涉及中心凹中心的色素沉着，但没有证据表明视网膜内/视网膜下新生血管。参与者还必须在研究眼(S)和面部椭圆区存在IS/OS PR中断，根据SDOCT测量 0.16mm2和4.00mm2。 设计：这是一项第2阶段的前瞻性、多中心、单掩蔽、假对照研究。所有参与者的筛选时间最长为14天。NT-501植入物的手术或假手术将在完成筛查后七周内进行。如果符合条件，参与者的双眼可以包括在研究中。有一只研究眼符合纳入标准的参与者将被随机(1：1)在符合研究条件的眼睛中接受NT-501植入或假手术。如果两只眼都符合条件，则右眼将被随机(1：1)接受NT-501植入物或假手术。左眼将接受替代手术/假手术。研究眼将在第0天接受NT-501植入物或假手术，并在第1天、第1周(2天)、第1个月(1周)、第3个月(1周)、第6个月(2周)、第12个月(2周)、第18个月(2周)和第24个月(2周)进行评估。 观察指标：主要结果将是研究眼(S)的面部SDOCT断层成像所测量的椭球区(IS/OS丢失面积)(24个月基线)的变化。研究NT-501产生的睫状神经营养因子(CNTF)疗效的次要结果包括(相对于基线测量的所有变化)：从基线到12个月椭球区(IS/OS丢失面积)的变化；从基线到12和24个月用微视野测量的视网膜敏感度(DB)的变化；在12和24个月时椭球区(IS/OS丢失面积)比基线增加35%或更多的研究眼的比例；从基线到12和24个月最佳矫正视力(BCVA)的变化；12个月和24个月BCVA的研究眼较基线丢失15个字母或更多字母的比例；12个月和24个月的BCVA研究眼较基线丢失10个或更多字母的比例；阅读速度从基线到12个月和24个月的变化。研究NT-501产生的睫状神经营养因子(CNTF)有效性的探索性结果包括(相对于基线测量的所有变化)：在选定的参与者中，AOSLO测量的视锥密度从基线到12个月和24个月的变化；NEI VFQ(总体和分量表)从基线到12个月和24个月的变化；选定诊所从基线到6个月、12个月和24个月的视网膜电图(ERG)变化。安全性将根据协议中定义的预先指定的安全结果进行评估。 我们于2014财年在NEI启动了这项研究。在2015财年，该试验达到了其应计目标，该研究的登记工作已经结束。NEI研究网站有六(6)名参与者注册。

Objective: The objective of this study is to investigate the effect of the ciliary neurotrophic factor (CNTF)-secreting NT-501 device on change from baseline in the area of macular ellipsoid zone disruption as measured by en face imaging by spectral domain optical coherence tomography (SD-OCT) in eyes with evidence of macular telangiectasia (MacTel) type 2 at 24 months. Study Population: Sixty-eight (68) participants with MacTel type 2 will be enrolled study wide. Up to 10 participants will be enrolled at NEI. Five participants will be included in the primary analysis; up to an additional five participants may be enrolled to account for participants who do not meet the eligibility criteria. Eligible participants will be adults, ages 21 to 80 years, who at the time of the screening visit have at least one study eye with a positive diagnosis of MacTel Type 2 with evidence of fluorescein leakage typical of MacTel or at least one of the other features including retinal opacification, crystalline deposits, right angle vessels, inner/outer lamellar cavities or hyperpigmentation not involving the center of the fovea, but no evidence of intraretinal/subretinal neovascularization. Participants must also have the presence of an IS/OS PR break in the study eye(s) and en face ellipsoid zone as measured by SDOCT between 0.16 mm2 and 4.00 mm2. Design: This is a Phase 2, prospective, multi-center, single-masked, sham-controlled study. All participants will have a screening period of up to 14 days. Surgery with the NT-501 implant or a sham procedure will occur within seven weeks after completing screening. Both eyes of the participants may be included in the study if eligible. Participants with one study eye that meets the inclusion criteria will be randomized (1:1) to receive the NT-501 implant or sham procedure in the study-eligible eye. If both eyes are eligible, then the right eye will be randomized (1:1) to receive the NT-501 implant or sham procedure. The left eye will receive the alternative surgery/sham. Study eyes will receive the NT-501 implant or sham procedure on Day 0 and will be assessed on Day 1, Week 1 ( 2 days), Month 1 ( 1 week), Month 3 ( 1 week), Month 6 ( 2 weeks), Month 12 ( 2 weeks), Month 18 ( 2 weeks) and Month 24 ( 2 weeks). Outcome Measures: The primary outcome will be change in the ellipsoid zone (area of IS/OS loss) (month 24 baseline) as measured by en face imaging by SDOCT in study eye(s). Secondary outcomes to investigate the efficacy of Ciliary Neurotrophic Factor (CNTF) produced by NT-501 include (all changes relative to baseline measurements): change in the ellipsoid zone (area of IS/OS loss) from baseline to Month 12; change in retinal sensitivity (dB) as measured by microperimetry from baseline to Months 12 and 24; proportion of study eyes with a 35% or more increase from baseline in the ellipsoid zone (area of IS/OS loss) at Months 12 and 24; change in best corrected visual acuity (BCVA) from baseline to Months 12 and 24; proportion of study eyes with 15 or more letter loss from baseline in BCVA at Months 12 and 24; proportion of study eyes with 10 or more letter loss from baseline in BCVA at Months 12 and 24; change in reading speed from baseline to Months 12 and 24. Exploratory outcomes to investigate the efficacy of Ciliary Neurotrophic Factor (CNTF) produced by NT-501 include (all changes relative to baseline measurements): change in cone density as measured by AOSLO from baseline to Months 12 and 24, in selected participants; change in NEI VFQ (overall and subscale) from baseline to Months 12 and 24; electroretinogram (ERG) changes from baseline to Months 6, 12 and 24, in selected clinics. Safety will be assessed by pre-specified safety outcomes as defined in the protocol. We initiated this study at the NEI in fiscal year 2014. In fiscal year 2015, the trial met its accrual goal, and enrollment in the study was closed. The NEI study site has six (6) participants enrolled.