Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON. Issue 1 (15th November 2022)

• Record Type: Journal Article
• Authors: Subramanian, Prem S; Newman, Nancy J; Moster, Mark; Wang, An-Guor; Yu-Wai-Man, Patrick; Donahue, Sean; Leroy, Bart P; Carelli, Valerio; Biousse, Valerie; Vignal-Clermont, Catherine; Sergott, Robert C; Sadun, Alfredo A; Rebolleda, Gema; Chwalisz, Bart K; Banik, Rudrani; Bazin, Fabienne; Cox, Eric; Roux, Michel; Taiel, Magali; Sahel, Jose-Alain
• Other Names: author non-byline.; Giulia Amore author non-byline.; Shweta Anand author non-byline.; Rudrani Banik author non-byline.; Piero Barboni author non-byline.; Valérie Biousse author non-byline.; Hayley Boston author non-byline.; Asma Burale author non-byline.; Michele Carbonelli author non-byline.; Valerio Carelli author non-byline.; Celia Chen author non-byline.; Hui-Chen Cheng author non-byline.; Steve Cho author non-byline.; Chwalisz Bart K author non-byline.; Manuela Contin author non-byline.; Pietro D'Agati author non-byline.; DeBusk Adam A author non-byline.; Julie De Zaeytijd author non-byline.; Jannah Dobbs author non-byline.; Donahue Sean P author non-byline.; Lindreth DuBois author non-byline.; Simona Esposti author non-byline.; Alcides Fernandes Filho author non-byline.; Elizabeth Fortin author non-byline.; Sapna Gangaputra author non-byline.; Deborah Gibbs author non-byline.; François Girmens Jean author non-byline.; Rabih Hage author non-byline.; Haller Julia A author non-byline.; Gad Heilweil author non-byline.; GeorgeBaker Hubbard III author non-byline.; Jeong-Min Hwang author non-byline.; Laia Jaumendreu Urquijo author non-byline.; Neringa Jurkute author non-byline.; Rustum Karanjia author non-byline.; Wahiba Khemliche author non-byline.; Chiara La Morgia author non-byline.; Leroy Bart P author non-byline.; Maria Massini author non-byline.; Marc Mathias author non-byline.; Memon Muhammad A author non-byline.; Susan Mohamed author non-byline.; Moster Mark L author non-byline.; Muñoz NegreteFrancisco J author non-byline.; Newman Nancy J author non-byline.; Ghazala O'Keefe author non-byline.; Shriji Patel author non-byline.; Paula Pecen author non-byline.; Peragallo Jason H author non-byline.; Lise Plaine author non-byline.; Mary Preston author non-byline.; Gema Rebolleda Fernández author non-byline.; Martina Romagnoli author non-byline.; Sadun Alfredo A author non-byline.; Sahel José A author non-byline.; Melissa SantaMaria author non-byline.; Sergott Robert C author non-byline.; Subramanian Prem S author non-byline.; Chuanbin Sun author non-byline.; Katy Tai author non-byline.; Heather Tollis author non-byline.; Irena Tsui author non-byline.; Tucker William R author non-byline.; Catherine Vignal-Clermont author non-byline.; An-Guor Wang author non-byline.; Saige Wilkins author non-byline.; Patrick Yu-Wai-Man author non-byline.;
• Is Part Of: BMJ open ophthalmology. Volume 7:Issue 1(2022)
• Publication Date: 2022-11-15
• Subjects: Clinical Trial -- Pathology -- Vision -- Drugs -- Retina; Ophthalmology -- Periodicals; 617.7005
• DOI: 10.1136/bmjophth-2022-001158
• Languages: English
• ISSNs: 2397-3269

Abstract

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.