Phase 2 Study of CNTF on Photoreceptor Structure in Retinitis Pigmentosa

描述（由申请人提供）： 遗传性视网膜变性包括视网膜色素变性（RP）和Usher综合征2型和3型是孤儿疾病。 视网膜变性导致视杆细胞和视锥细胞的进行性死亡，伴随着无情的视力丧失和最终失明。 没有治愈方法，有效的治疗方法非常有限。 神经营养因子如睫状神经营养因子（CNTF）在动物模型和患者中显示出减缓视网膜变性的前景。一项1期研究和两项2期研究显示，通过包封细胞技术（NT-501）玻璃体内植入物在遗传性视网膜变性患者中提供的持续释放CNTF可能是安全的，耐受性良好。 然而，在长达24个月的研究期间，在CNTF或对侧假手术治疗的眼睛中均未观察到视力的显著变化。 由于活体眼睛的光学缺陷，标准的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）可以在视网膜变性的眼睛中产生个体视锥光感受器的图像。使用AOSLO对少数遗传性视网膜变性患者的视锥成像的初步研究显示，与接受假治疗的对侧眼相比，接受CNTF治疗的眼睛的视锥丢失率降低。然而，CNTF治疗的眼睛没有显示出视力或视野敏感性的改善，这可能是因为视觉功能的标准测量的分辨率低于使用AOSLO获得的单个视锥细胞的图像。 视网膜结构和视觉功能的更高分辨率的措施是必要的，以确定CNTF是否有效地减缓感光细胞的损失和保护视觉功能。 这项前瞻性、2期、双盲、假对照研究的目的是评价NT-501装置递送的CNTF在24个月内减缓RP和Usher综合征2型和3型患者锥体光感受器丧失的安全性和有效性。 将20名患者随机分配，一只眼睛接受NT-501器械，对侧眼睛接受假手术。 患者将在基线时进行两次研究，然后在植入CNTF释放NT-501装置后6、12、18、24和30个月进行研究。 主要结局指标是使用AOSLO证明CNTF治疗眼与假治疗眼相比在24个月时锥状感光细胞存活率的改善。 这项研究将验证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。

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.