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.

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. 研究人群：六十八名（68）型Mactel 2型的参与者将被纳入研究。最多将有10名参与者参加NEI。主要分析将包括五名参与者；最多可能会招募另外五名参与者，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，在筛查时，他们至少有一个研究眼睛，对MACTEL 2型的2型研究眼睛具有阳性诊断，并有典型的Mactel荧光素泄漏的证据，或者至少有一个其他特征，包括视网膜渗透，晶体沉积物，晶体内/外部/外部/外部/超叶型的荧光症，包括视网膜渗透或其他特征。视网膜内/视网膜下新血管形成。参与者还必须在研究眼中存在IS/OS PR断裂，并通过SDOCT在 0.16 mm2和4.00 mm2。 设计：这是2阶段，前瞻性，多中心，单掩蔽，假手术的研究。所有参与者的筛查期最长为14天。 NT-501植入物或假手术的手术将在完成筛查后的七个星期内进行。如果符合条件，则可能包括参与者的两只眼睛。符合纳入标准的一只研究眼的参与者将被随机分组​​（1：1），以在符合研究资格的眼睛中接受NT-501植入物或假手术。如果两只眼睛都有资格，则将右眼随机（1：1）接收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周（2周），第12周（2周），第18个月（2周），第2周（2周）和月24（2周（2周）。 结果指标：主要结果将是通过SDOCT在研究眼中进行的EN面对成像测量的椭圆形区域（IS/OS损失区域）（IS/OS损失的区域）（基线24个月）。 NT-501产生的睫状神经营养因子（CNTF）的效力包括（相对于基线测量值的所有变化）：椭圆形区域的变化（IS/OS损失面积）从基线到12个月的变化；从基线到第12和24个月测量的视网膜灵敏度（DB）的变化；在第12和第24个月的椭圆形区域（IS/OS损失的区域）中，研究眼比基线增加了35％或更高；最佳校正视力（BCVA）从基线变为第12和24个月；研究眼比例为BCVA在第12和24个月的基线中有15个或更多字母损失；在BCVA的第12和24个月的基线损失10个或更多字母的研究眼睛的比例； NT-501产生的睫状神经营养因子（CNTF）的效果的探索结果的变化从基线到第12和第24个月。NT-501产生的睫状性神经营养因子（CNTF）的功效包括（相对于基线测量值的所有变化）：由AOSLO从基线到基线到第12和24个月的锥密度变化，在选定的参与者中，在选定的参与者中； NEI VFQ（总体和子量表）的变化从基线到第12和24个月；电子图（ERG）在选定的诊所中从基线变为第6、12和24个月。安全性将通过协议中定义的预先指定的安全结果进行评估。 我们在2014财政年度的NEI开始了这项研究。在2015财年，该试验实现了其六（6）名参与者的应计目标，并关闭了该研究的入学人数。 在2017财政年度，参与者在2年时达到了试验的主要终点，结果进行了分析。