Phase 2 Study of CNTF on Photoreceptor Structure in Retinitis Pigmentosa

CNTF 对色素性视网膜炎感光器结构的二期研究

• 批准号: 8355123
• 负责人: JACQUE LYNNE DUNCAN
• 金额: $ 38.97万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8355123
• 关键词: Phase; Study; CNTF; Photoreceptor; Structure

DESCRIPTION (provided by applicant): Inherited retinal degenerations including retinitis pigmentosa (RP) and Usher Syndrome Types 2 and 3 are orphan diseases. Retinal degenerations cause progressive death of rod and cone photoreceptors with relentless vision loss and ultimate blindness. There are no cures, and effective treatments are extremely limited. Neurotrophic factors such as ciliary neurotrophic factor (CNTF) have shown promise in slowing retinal degeneration in animal models and patients. A Phase 1 study and two Phase 2 studies of sustained-release CNTF delivered by an encapsulated cell technology (NT-501) intravitreal implant in patients with inherited retinal degeneration showed CNTF may be safe and well-tolerated. However, no significant change in vision was observed in either the CNTF or contralateral sham-treated eyes over study periods up to 24 months. Standard clinical imaging techniques cannot visualize individual photoreceptors due to optical imperfections in living eyes. However, adaptive optics scanning laser ophthalmoscopy (AOSLO) can produce images of individual cone photoreceptors in eyes with retinal degeneration. Preliminary studies using AOSLO to image cones in a small number of patients with inherited retinal degenerations showed reduced rates of cone loss in eyes treated with CNTF compared to contralateral eyes that received sham treatment. However, CNTF-treated eyes showed no improvement in visual acuity or visual field sensitivity, perhaps because standard measures of visual function are of lower resolution than the images of individual cones obtained using AOSLO. Higher resolution measures of retinal structure and visual function are necessary to determine whether CNTF is effective in slowing photoreceptor loss and preserving visual function. The objective of this prospective, Phase 2, double-masked, sham-controlled study is to evaluate the safety and efficacy of CNTF delivered by the NT-501 device to slow cone photoreceptor loss in patients with RP and Usher syndrome types 2 and 3 over 24 months. Twenty patients will be randomized to receive the NT-501 device in one eye and sham surgery in the contralateral eye. Patients will be studied twice at baseline, then at 6, 12, 18, 24 and 30 months after implantation of the CNTF-releasing NT-501 device. The primary outcome measure is demonstration of improvement in cone photoreceptor survival in CNTF-treated eyes compared to sham-treated eyes at 24 months using AOSLO. The study will test the hypothesis that CNTF is safe and effective in preventing vision cell death and blindness in patients with inherited retinal degenerations.

描述（由申请人提供）： 遗传性视网膜变性，包括色素性视网膜炎 (RP) 和 2 型和 3 型亚瑟综合征，均为孤儿疾病。 视网膜变性导致视杆细胞和视锥细胞感光细胞进行性死亡，导致视力持续丧失并最终失明。 目前尚无治愈方法，有效的治疗方法也极其有限。 睫状神经营养因子（CNTF）等神经营养因子已在动物模型和患者中显示出减缓视网膜变性的希望。一项针对遗传性视网膜变性患者通过封装细胞技术 (NT-501) 玻璃体内植入物递送缓释 CNTF 的 1 期研究和两项 2 期研究表明，CNTF 可能是安全且耐受性良好的。 然而，在长达 24 个月的研究期间，CNTF 或对侧假治疗眼均未观察到视力发生显着变化。 由于活体眼睛的光学缺陷，标准临床成像技术无法可视化单个光感受器。然而，自适应光学扫描激光检眼镜 (AOSLO) 可以生成视网膜变性眼睛中单个视锥细胞感光器的图像。使用 AOSLO 对少数患有遗传性视网膜变性的患者进行视锥细胞成像的初步研究表明，与接受假治疗的对侧眼睛相比，接受 CNTF 治疗的眼睛的视锥细胞损失率降低。然而，经过 CNTF 处理的眼睛在视力或视野敏感性方面没有表现出任何改善，这可能是因为视觉功能的标准测量方法的分辨率低于使用 AOSLO 获得的单个视锥细胞的图像。 需要对视网膜结构和视觉功能进行更高分辨率的测量，以确定 CNTF 是否能有效减缓感光器损失和保留视觉功能。 这项前瞻性、第 2 期、双盲、假对照研究的目的是评估 NT-501 装置提供的 CNTF 在 24 个月内减缓 RP 和 Usher 综合征 2 型和 3 型患者视锥光感受器损失的安全性和有效性。 20 名患者将被随机分配，一只眼睛接受 NT-501 装置，另一只眼睛接受假手术。 患者将在基线时接受两次研究，然后在植入释放 CNTF 的 NT-501 装置后 6、12、18、24 和 30 个月进行研究。 主要结果指标是使用 AOSLO 24 个月时，与假治疗眼睛相比，CNTF 治疗眼睛的视锥光感受器存活率有所改善。 该研究将验证 CNTF 在预防遗传性视网膜变性患者视觉细胞死亡和失明方面安全有效的假设。