Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ ND4-LHON

• Type of Material: Article
• Authors: Prem S Subramanian, University of Colorado Anschutz Medical Campus; Nancy Newman, Emory University; Mark Moster, Wills Eye Hospital; An-Guor Wang, Veterans General Hospital-Taipei; Patrick Yu-Wai-Man, University of Cambridge; Seab Donahue, Vanderbilt Eye Institute; BP Leroy, Universitair Ziekenhuis Gent; Valerio Carelli, Istituto delle Scienze Neurologiche di Bologna; Valerie Biousse, Emory University; Catherine Vignal-Clermont, Fondation Adolphe de Rothschild; Robert C Sergott, Wills Eye Hospital; Alfredo A Sadun, David Geffen School of Medicine at UCLA; Gema Rebolleda, Hospital Universitario Ramón y Cajal; Bart K Chwalisz, Massachusetts Eye and Ear Infirmary; Rudrani Banik, Icahn School of Medicine at Mount Sinai; Fabienne Bazin, eXYSTAT; Eric Cox, GenSight Biologics; Michel Roux, GenSight Biologics; Magali Taiel, GenSight Biologics SA; Jose-Alain Sahel, Institut de la Vision
• Language: English
• Date: 2022-11-15
• Publisher: BMJ
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/bmjophth-2022-001158
• Title of Journal or Parent Work: BMJ Open Ophthalmology
• Volume: 7
• Issue: 1
• Grant/Funding Information: This study was funded by Gensight Biologics.
• Keywords: reflect gene therapy trial
• Research Categories: Health Sciences, Opthamology

Abstract

Objective REFLECT is the first randomised, double-masked, placebo-controlled multicentre phase 3 clinical trial that evaluated the efficacy and safety of bilateral intravitreal (IVT) injection of lenadogene nolparvovec in subjects with Leber hereditary optic neuropathy carrying the m.11778G>A mutation. Methods and analysis A total of 98 subjects were enrolled with vision loss of ≤12 months. The subjects were randomised to one of two treatment arms with all subjects receiving an intravitreal (IVT) injection of lenadogene nolparvovec in their first affected eye and the second-affected eye randomised to receive IVT of either lenadogene nolparvovec or placebo. Results The majority of subjects were male with a mean duration of vision loss of 8.3 months. All but one subject experienced bilateral loss of vision at the time of injection. The mean best-corrected visual acuity of first-affected eyes was worse compared with second/not-yet-affected eyes. Analysis of retinal anatomical parameters showed increased thinning in the first-affected eyes when compared with the second/not-yet-affected eyes with both treatment arms showing significant changes compared with unaffected individuals. Conclusion The REFLECT trial is the third and the largest phase 3 clinical study evaluating lenadogene nolparvovec in m.11778G>A Leber hereditary optic neuropathy (LHON) subjects. The observed demographics in REFLECT are consistent with previous reports in LHON subjects in the acute and dynamic phases of LHON disease. Combined with the visual function and anatomical parameters obtained in the previous RESCUE and REVERSE trials, REFLECT has provided a uniformly collected data set that should help direct future LHON clinical trials.