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型的Usher综合征是孤儿疾病。 视网膜变性会导致杆和锥形感受器的渐进死亡，具有无情的视力丧失和最终的失明。 没有治疗方法，有效的治疗非常有限。 诸如睫状神经营养因子（CNTF）之类的神经营养因子在动物模型和患者的视网膜变性缓慢方面表现出了希望。遗传性视网膜变性患者的封装细胞技术（NT-501）提供的持续释放CNTF的持续释放CNTF的两期研究表明，CNTF可能是安全且耐受性良好的。 但是，在长达24个月的研究期间，在CNTF或对侧模拟的眼睛对对面进行的眼睛的眼睛中，视力均未观察到显着变化。 由于活着的眼睛中的光学缺陷，标准的临床成像技术无法可视化单个感光体。但是，自适应光学扫描激光眼镜检查（AOSLO）可以在视网膜变性的眼睛中产生单个锥形感受器的图像。与接受假治疗的对侧眼睛相比，使用AOSLO对少数遗传性视网膜变性患者的锥体锥体损失率的初步研究显示，用CNTF治疗的眼睛损失率降低了。但是，经CNTF处理的眼睛没有显示视力或视野灵敏度的改善，这可能是因为视觉功能的标准测量值比使用AOSLO获得的单个锥体的图像低分辨率。 为了确定CNTF是否有效减慢感光体丢失和保留视觉功能，必须采取更高的视网膜结构和视觉功能的测量。 该前瞻性2阶段，双掩盖的假手术研究的目的是评估NT-501设备在24个月内使用NT-501设备在RP和USHER综合征2型和3型患者中慢慢锥形光感受器损失的CNTF的安全性和功效。 将有20名患者在一只眼睛中随机接收NT-501装置，并在对侧眼中进行假手术。 将在基线时进行两次研究，然后在植入CNTF释放NT-501设备后的6、12、18、24和30个月。 与使用AOSLO在24个月相比，CNTF处理的眼睛相比，CNTF处理的眼睛中锥形光感受器生存的改善的主要结果指标是证明了锥形感光受体存活率的改善。 该研究将检验以下假设：CNTF可以安全有效地预防视网膜退化患者的视力细胞死亡和失明。