TY - JOUR T1 - Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g&gt;A/<em>ND4</em>-LHON JF - BMJ Open Ophthalmology JO - BMJ Open Ophth DO - 10.1136/bmjophth-2022-001158 VL - 7 IS - 1 SP - e001158 AU - Prem S Subramanian AU - Nancy J Newman AU - Mark Moster AU - An-Guor Wang AU - Patrick Yu-Wai-Man AU - Sean Donahue AU - Bart P Leroy AU - Valerio Carelli AU - Valerie Biousse AU - Catherine Vignal-Clermont AU - Robert C Sergott AU - Alfredo A Sadun AU - Gema Rebolleda AU - Bart K Chwalisz AU - Rudrani Banik AU - Fabienne Bazin AU - Eric Cox AU - Michel Roux AU - Magali Taiel AU - Jose-Alain Sahel A2 - , Y1 - 2022/11/01 UR - http://bmjophth.bmj.com/content/7/1/e001158.abstract N2 - 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&gt;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&gt;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.Data are available on reasonable request. ER -