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

目的：本研究的目的是研究睫状神经营养因子（CNTF）分泌NT-501装置对24个月时具有2型黄斑毛细血管扩张（MacTel）证据的眼睛中黄斑椭圆区破坏面积相对于基线变化的影响，该变化通过面成像光谱域光学相干断层扫描（SD-OCT）测量。 研究人群：研究范围内将入组68例MacTel 2型受试者。最多10名参与者将在NEI注册。主要分析将纳入5例受试者;最多可再入组5例受试者，以说明不符合合格标准的受试者。合格的参与者将是年龄为21至80岁的成年人，在筛选访视时至少有一只研究眼被诊断为MacTel 2型阳性，有MacTel典型的荧光素渗漏证据或至少一种其他特征，包括视网膜混浊、结晶沉积物、直角血管、内/外板层腔或不涉及中央凹中心的色素沉着过度，但没有视网膜内/视网膜下新生血管形成的证据。受试者还必须在研究眼和正面椭圆体区存在IS/OS PR断裂（通过SDOCT测量）， 0.16 mm 2和4.00 mm 2。 设计：这是一项2期、前瞻性、多中心、单盲、假手术对照研究。所有参与者将有长达14天的筛选期。NT-501植入物手术或假手术将在完成筛选后7周内进行。如果合格，参与者的双眼都可以纳入研究。一只研究眼符合入选标准的受试者将随机（1：1）接受NT-501植入或假手术。如果双眼均合格，则右眼将随机（1：1）接受NT-501植入或假手术。左眼将接受替代手术/假手术。研究眼将在第0天接受NT-501植入或假手术，并将在第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。 结局指标：主要结局将是研究眼的椭圆体区（IS/OS损失面积）（第24个月基线）的变化，通过SDOCT的正面成像测量。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（相对于基线测量值的所有变化）：椭球区的变化从基线至第12个月（IS/OS损失的面积）;通过微视野检查法测量的从基线至第12个月和第24个月的视网膜灵敏度（dB）的变化;椭球体区较基线增加35%或以上的研究眼比例（IS/OS损失面积）;从基线至第12个月和第24个月的最佳矫正视力（BCVA）变化;第12个月和第24个月时BCVA较基线丢失15个或以上字母的研究眼比例;第12个月和第24个月时BCVA较基线丢失10个或以上字母的研究眼比例;第12个月和第24个月时阅读速度较基线的变化。研究NT-501产生的睫状神经营养因子（CNTF）功效的探索性结果包括（相对于基线测量值的所有变化）：在选定的受试者中，通过AOSLO测量的视锥细胞密度从基线至第12个月和第24个月的变化; NEI VFQ（总体和子量表）从基线至第12个月和第24个月;选定诊所中视网膜电图（ERG）从基线至第6、12和24个月的变化。将通过方案中规定的预先规定的安全性结局评估安全性。 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，研究的入组已关闭。 NEI研究中心入组了6名受试者。

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.