Jeffrey S Heier1, Allen C Ho2, Michael A Samuel3, Tom Chang3, Christopher D Riemann4, John W Kitchens5, Jason S Slakter6, Yannek I Leiderman7, Rand Spencer8, George A Williams9, Sheila B Hickson-Curran10, Michael Keane10, James S Baldassarre10. 1. Ophthalmic Consultants of Boston, Boston, Massachusetts. Electronic address: JSHEIER@eyeboston.com. 2. Wills Eye Hospital/Mid Atlantic Retina, Philadelphia, Pennsylvania. 3. Retina Institute of California, Pasadena, California. 4. Cincinnati Eye Institute & University of Cincinnati, Cincinnati, Ohio. 5. Retina Associates of Kentucky, Lexington, Kentucky. 6. Vitreous Retina Macula Consultants of New York, New York, New York. 7. University of Illinois Eye and Ear Infirmary, Chicago, Illinois. 8. Texas Retina Associates, Dallas, Texas. 9. Department of Ophthalmology, Oakland University William Beaumont School of Medicine, Rochester, Michigan. 10. Janssen Research & Development, Spring House, Pennsylvania.
Abstract
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 × 105 cells in 50 μl, 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 mm2 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.
RCT Entities:
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 × 105 cells in 50 μl, 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 mm2 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.
Authors: Benjamin J Kim; Allan Hunter; Alexander J Brucker; Paul Hahn; Karen Gehrs; Apurva Patel; Albert O Edwards; Yafeng Li; Rahul N Khurana; Itzhak Nissim; Ebenezer Daniel; Juan Grunwald; Gui-Shuang Ying; Maxwell Pistilli; Maureen G Maguire; Joshua L Dunaief Journal: Ophthalmol Retina Date: 2020-04-02
Authors: Tien-En Tan; Beau James Fenner; Veluchamy Amutha Barathi; Sai Bo Bo Tun; Yeo Sia Wey; Andrew Shih Hsiang Tsai; Xinyi Su; Shu Yen Lee; Chui Ming Gemmy Cheung; Tien Yin Wong; Jodhbir Singh Mehta; Kelvin Yi Chong Teo Journal: Front Genet Date: 2021-12-07 Impact factor: 4.599
Authors: Ananth Sastry; Jianwei D Li; William Raynor; Christian Viehland; Zhenxi Song; Liangyu Xu; Sina Farsiu; Joseph A Izatt; Cynthia A Toth; Lejla Vajzovic Journal: Transl Vis Sci Technol Date: 2021-06-01 Impact factor: 3.283