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

睫状神经营养因子 (CNTF) 治疗 2 型黄斑毛细血管扩张症 (MacTel) 的 2 期多中心随机临床试验 (14-EI-0078)

• 批准号: 9555705
• 负责人: Henry Wiley
• 金额: $ 5.78万
• 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/9555705
• 关键词: Adult; Affect; Age; Area; Blindness; Ciliary Neurotrophic Factor; Clinic; Clinical Trials; Cone; Degenerative Disorder; Deposition; Devices; Diagnosis; Disease; Electroretinography; Eligibility Determination; Enrollment; Extravasation; Eye; Fluorescein; Goals; Hyperpigmentation; Image; Implant; Left; Letters; Masks; Measurement; Measures; Operative Surgical Procedures; Optical Coherence Tomography; Outcome; Outcome Measure; Participant; Phase; Procedures; Protocols documentation; Randomized; Randomized Clinical Trials; Reading; Retina; Retinal; Safety; Specific qualifier value; Speed; Telangiectasis; Visit; Visual Acuity; adaptive optics scanning laser ophthalmoscopy; crystallinity; density; design; eligible participant; fovea centralis; inclusion criteria; macula; neovascularization; primary outcome; prospective; screening; secondary outcome; sham surgery; sham-controlled study; spectrograph; study population; tv watching

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 of six (6) participants, and enrollment in the study was closed. In fiscal year 2017, participants reached the primary endpoint of the trial at 2 years, and analysis of results is in progress.

目的：本研究的目的是探讨分泌睫状神经营养因子 (CNTF) 的 NT-501 装置对 24 个月时有 2 型黄斑毛细血管扩张 (MacTel) 证据的眼睛通过谱域光学相干断层扫描 (SD-OCT) 正面成像测量黄斑椭球体区破坏区域相对基线变化的影响。 研究人群：将在整个研究范围内招募六十八 (68) 名 MacTel 2 型参与者。 NEI 最多可招收 10 名参与者。初步分析将包括五名参与者；对于不符合资格标准的参与者，最多可额外登记五名参与者。符合资格的参与者为年龄 21 至 80 岁的成年人，在筛选访视时至少一只研究眼被诊断为 MacTel 2 型阳性，并有 MacTel 典型荧光素渗漏的证据，或至少一种其他特征，包括视网膜浑浊、结晶沉积、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，但没有证据表明 视网膜内/视网膜下新生血管形成。参与者还必须在研究眼睛和面部椭球区中存在 IS/OS PR 中断（通过 SDOCT 测量） 0.16 毫米2 和4.00 毫米2。 设计：这是一项 2 期、前瞻性、多中心、单盲、假对照研究。所有参与者都将接受长达 14 天的筛选期。 NT-501 植入手术或假手术将在完成筛选后七周内进行。如果符合条件，参与者的双眼均可参与研究。一只研究眼睛符合纳入标准的参与者将被随机 (1:1) 地在符合研究条件的眼睛中接受 NT-501 植入或假手术。如果双眼均符合条件，则右眼将被随机 (1:1) 接受 NT-501 植入或假手术。左眼将接受替代手术/假手术。研究眼睛将在第 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。 结果测量：主要结果是椭圆体区域（IS/OS 丢失区域）（第 24 个月基线）的变化，通过 SDOCT 在研究眼睛中进行面部成像测量。研究 NT-501 产生的睫状神经营养因子 (CNTF) 功效的次要结果包括（与基线测量相关的所有变化）： 从基线到第 12 个月的椭球区（IS/OS 损失区域）的变化；通过显微视野测量从基线到第 12 个月和第 24 个月的视网膜敏感度变化 (dB)；第 12 个月和第 24 个月时，椭圆体区（IS/OS 损失区域）较基线增加 35% 或更多的研究眼睛比例；最佳矫正视力 (BCVA) 从基线到第 12 个月和第 24 个月的变化；第 12 个月和第 24 个月时 BCVA 较基线丢失 15 个或更多字母的研究眼睛的比例；第 12 个月和第 24 个月时 BCVA 较基线丢失 10 个或更多字母的研究眼睛的比例；阅读速度从基线到第 12 个月和第 24 个月的变化。调查 NT-501 产生的睫状神经营养因子 (CNTF) 功效的探索性结果包括（所有与基线测量相关的变化）： 在选定的参与者中，由 AOSLO 测量的视锥细胞密度从基线到第 12 个月和第 24 个月的变化； NEI VFQ（总体和分量表）从基线到第 12 个月和第 24 个月的变化；在选定的诊所中，视网膜电图 (ERG) 从基线到第 6、12 和 24 个月发生了变化。安全性将根据方案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。2015 财年，该试验达到了六 (6) 名参与者的累积目标，并且该研究的招募已结束。 2017 财年，参与者在 2 年后达到了试验的主要终点，结果分析正在进行中。