PMID- 32033908 OWN - NLM STAT- MEDLINE DCOM- 20210518 LR - 20210518 IS - 2468-6530 (Electronic) IS - 2468-6530 (Linking) VI - 4 IP - 4 DP - 2020 Apr TI - Safety and Efficacy of Subretinally Administered Palucorcel for Geographic Atrophy of Age-Related Macular Degeneration: Phase 2b Study. PG - 384-393 LID - S2468-6530(19)30635-9 [pii] LID - 10.1016/j.oret.2019.11.011 [doi] AB - PURPOSE: To evaluate safety and successful use of a novel subretinal delivery system and suprachoroidal surgical approach and safety and activity of human umbilical tissue-derived cells (palucorcel) via a novel delivery system in patients with geographic atrophy (GA). DESIGN: Multicenter, open-label phase 2b study. PARTICIPANTS: Participants were 55 to 90 years with GA secondary to age-related macular degeneration (AMD) and best-corrected visual acuity (BCVA) of 20/80 to 20/800. Exclusion criteria included neovascular AMD in the intervention eye, glaucoma with intraocular pressure of 25 mmHg or more, or other significant ophthalmologic conditions. METHODS: Participants received a subretinal injection of palucorcel, 3.0 x 10(5) cells in 50 mul, using the custom-designed delivery system and surgical procedure. MAIN OUTCOME MEASURES: Safety assessments included treatment-emergent adverse events (AEs), immunologic assessments, and ophthalmologic evaluations. Efficacy was evaluated as change in mean number of BCVA letters from baseline, proportion of participants gaining 15 BCVA letters or more, and growth rate of GA lesions at 12 months. RESULTS: Surgery and palucorcel administration were performed in 21 participants at 8 sites by 8 different surgeons. At baseline, median total area of GA was 13.4 mm(2) and median BCVA was 43 letters in the intervention eye. Eye-related AEs occurred in 76% of participants (16/21), including conjunctival hemorrhage (n = 5), retinal hemorrhage (n = 4), and vitreous floaters (n = 4). Most AEs were mild and resolved within 1 month. No serious AEs, no retinal detachment or perforation, and no significant changes in intraocular pressure occurred. At month 12, mean change in BCVA from baseline was -5.9 letters correct (standard deviation, 13.0 letters correct) in the intervention eye and -3.7 letters correct (standard deviation, 9.0 letters correct) in the fellow eye. No participants showed improvement of 15 letters or more in the intervention eye, and 3 participants lost more than 15 letters by month 1. No apparent effect of treatment was observed. CONCLUSIONS: Palucorcel was delivered successfully to the targeted subretinal site using a novel delivery system and suprachoroidal approach for most participants; however, improvement in GA area, retardation of growth, or visual acuity were not demonstrated. CI - Copyright (c) 2019. Published by Elsevier Inc. FAU - Heier, Jeffrey S AU - Heier JS AD - Ophthalmic Consultants of Boston, Boston, Massachusetts. Electronic address: JSHEIER@eyeboston.com. FAU - Ho, Allen C AU - Ho AC AD - Wills Eye Hospital/Mid Atlantic Retina, Philadelphia, Pennsylvania. FAU - Samuel, Michael A AU - Samuel MA AD - Retina Institute of California, Pasadena, California. FAU - Chang, Tom AU - Chang T AD - Retina Institute of California, Pasadena, California. FAU - Riemann, Christopher D AU - Riemann CD AD - Cincinnati Eye Institute & University of Cincinnati, Cincinnati, Ohio. FAU - Kitchens, John W AU - Kitchens JW AD - Retina Associates of Kentucky, Lexington, Kentucky. FAU - Slakter, Jason S AU - Slakter JS AD - Vitreous Retina Macula Consultants of New York, New York, New York. FAU - Leiderman, Yannek I AU - Leiderman YI AD - University of Illinois Eye and Ear Infirmary, Chicago, Illinois. FAU - Spencer, Rand AU - Spencer R AD - Texas Retina Associates, Dallas, Texas. FAU - Williams, George A AU - Williams GA AD - Department of Ophthalmology, Oakland University William Beaumont School of Medicine, Rochester, Michigan. FAU - Hickson-Curran, Sheila B AU - Hickson-Curran SB AD - Janssen Research & Development, Spring House, Pennsylvania. FAU - Keane, Michael AU - Keane M AD - Janssen Research & Development, Spring House, Pennsylvania. FAU - Baldassarre, James S AU - Baldassarre JS AD - Janssen Research & Development, Spring House, Pennsylvania. CN - Prelude Study Group LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191119 PL - United States TA - Ophthalmol Retina JT - Ophthalmology. Retina JID - 101695048 SB - IM MH - Cell- and Tissue-Based Therapy/*methods MH - Fluorescein Angiography MH - Follow-Up Studies MH - Fundus Oculi MH - Geographic Atrophy/diagnosis/etiology/*therapy MH - Humans MH - Injections, Intraocular MH - Macula Lutea/*pathology MH - Retina MH - Tomography, Optical Coherence MH - Treatment Outcome MH - *Visual Acuity MH - Wet Macular Degeneration/*complications/diagnosis EDAT- 2020/02/09 06:00 MHDA- 2021/05/19 06:00 CRDT- 2020/02/09 06:00 PHST- 2019/04/11 00:00 [received] PHST- 2019/11/11 00:00 [revised] PHST- 2019/11/12 00:00 [accepted] PHST- 2020/02/09 06:00 [pubmed] PHST- 2021/05/19 06:00 [medline] PHST- 2020/02/09 06:00 [entrez] AID - S2468-6530(19)30635-9 [pii] AID - 10.1016/j.oret.2019.11.011 [doi] PST - ppublish SO - Ophthalmol Retina. 2020 Apr;4(4):384-393. doi: 10.1016/j.oret.2019.11.011. Epub 2019 Nov 19.