RT Journal Article SR Electronic T1 Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON JF BMJ Open Ophthalmology JO BMJ Open Ophth FD BMJ Publishing Group Ltd SP e001158 DO 10.1136/bmjophth-2022-001158 VO 7 IS 1 A1 Prem S Subramanian A1 Nancy J Newman A1 Mark Moster A1 An-Guor Wang A1 Patrick Yu-Wai-Man A1 Sean Donahue A1 Bart P Leroy A1 Valerio Carelli A1 Valerie Biousse A1 Catherine Vignal-Clermont A1 Robert C Sergott A1 Alfredo A Sadun A1 Gema Rebolleda A1 Bart K Chwalisz A1 Rudrani Banik A1 Fabienne Bazin A1 Eric Cox A1 Michel Roux A1 Magali Taiel A1 Jose-Alain Sahel A1 , YR 2022 UL http://bmjophth.bmj.com/content/7/1/e001158.abstract AB 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.Data are available on reasonable request.