目的:报告晚期地理萎缩(GA)患者基于支架的人胚胎干细胞衍生视网膜色素上皮(RPE)植入物的1/2a期临床试验评估的长期结果。
方法:该研究是美国食品和药物管理局(FDA)批准的单臂,开放标签1/2a期临床试验。
方法:受试者在招募时年龄在69至85岁之间,并且由于涉及中央凹的GA,在治疗的眼睛中合法失明(最佳矫正视力(BCVA)≤20/200)。
方法:临床试验招募了16名受试者,其中15人成功植入。使用定制的视网膜下插入装置将植入物施用于视力较差的眼睛。伴随的非植入眼睛用作对照。主要终点为1年;此后受试者至少每年随访一次。
方法:安全性是研究的主要终点。不良事件的发生和频率由预定的眼科检查确定。包括BCVA的测量,眼内压,和多模态成像(眼底摄影,光学相干层析成像,和荧光素血管造影)。此外,收集血清抗体滴度以监测对植入细胞的全身体液免疫反应。
结果:中位随访时间为3年,眼底照相显示植入物没有迁移。没有意想不到的,严重,在整个随访期间,植入物相关的不良事件,最常见的预期严重不良事件(严重视网膜出血)在第二组(9名受试者)中通过使用改良术中止血消除.非严重,如视网膜下手术所预期的,所有受试者术中或术后均出现短暂性视网膜出血.在整个3年的中位随访中,结果表明,植入的眼睛更有可能改善>5个字母的BCVA,与未植入的眼睛相比,减少5个字母的可能性较小。
结论:本报告详细介绍了接受基于支架的干细胞衍生的生物工程RPE植入物的最大的GA受试者的长期随访研究。结果表明,植入物,在3年的中位随访中,在患有晚期干性AMD的受试者中是安全且耐受性良好的。安全简介,随着疗效的早期指征,有必要对这种治疗GA的新方法进行进一步的临床评估。
OBJECTIVE: To report long-term results from a phase 1/2a clinical
trial assessment of a scaffold-based human embryonic stem cell-derived retinal pigmented epithelium (RPE) implant in patients with advanced geographic atrophy (GA).
METHODS: A single-arm, open-label phase 1/2a clinical
trial approved by the United States Food and Drug Administration.
METHODS: Patients were 69-85 years of age at the time of enrollment and were legally blind in the treated eye (best-corrected visual acuity [BCVA], ≤ 20/200) as a result of GA involving the fovea.
METHODS: The clinical
trial enrolled 16 patients, 15 of whom underwent implantation successfully. The implant was administered to the worse-seeing eye with the use of a custom subretinal insertion device. The companion nonimplanted eye served as the control. The primary endpoint was at 1 year; thereafter, patients were followed up at least yearly.
METHODS: Safety was the primary endpoint of the
study. The occurrence and frequency of adverse events (AEs) were determined by scheduled eye examinations, including measurement of BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were collected to monitor systemic humoral immune responses to the implanted cells.
RESULTS: At a median follow-up of 3 years, fundus photography revealed no migration of the implant. No unanticipated, severe, implant-related AEs occurred, and the most common anticipated severe AE (severe retinal hemorrhage) was eliminated in the second cohort (9 patients) through improved intraoperative hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or after surgery in all patients as anticipated for a subretinal surgical procedure. Throughout the median 3-year follow-up, results show that implanted eyes were more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 5 letters compared with nonimplanted eyes.
CONCLUSIONS: This report details the long-term follow-up of patients with GA to receive a scaffold-based stem cell-derived bioengineered RPE implant. Results show that the implant, at a median 3-year follow-up, is safe and well tolerated in patients with advanced dry age-related macular degeneration. The safety profile, along with the early indication of efficacy, warrants further clinical evaluation of this novel approach for the treatment of GA.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.