BMJ Open Ophthalmology (Oct 2022)
Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON
- Nancy J Newman,
- Valérie Biousse,
- José-Alain Sahel,
- Patrick Yu-Wai-Man,
- Sean Donahue,
- Gema Rebolleda,
- Prem S Subramanian,
- Bart P Leroy,
- Alfredo A Sadun,
- Robert C Sergott,
- Catherine Vignal-Clermont,
- Bart K Chwalisz,
- Mark Moster,
- An-Guor Wang,
- Valerio Carelli,
- Rudrani Banik,
- Fabienne Bazin,
- Eric Cox,
- Michel Roux,
- Magali Taiel,
- Amore Giulia,
- Anand Shweta,
- Banik Rudrani,
- Barboni Piero,
- Biousse Valérie,
- Boston Hayley,
- Burale Asma,
- Carbonelli Michele,
- Carelli Valerio,
- Chen Celia,
- Cheng Hui-Chen,
- Cho Steve,
- K Chwalisz Bart,
- Contin Manuela,
- D’Agati Pietro,
- A DeBusk Adam,
- De Zaeytijd Julie,
- Dobbs Jannah,
- P Donahue Sean,
- DuBois Lindreth,
- Esposti Simona,
- Fernandes Filho Alcides,
- Fortin Elizabeth,
- Gangaputra Sapna,
- Gibbs Deborah,
- Girmens Jean François,
- Hage Rabih,
- A Haller Julia,
- Heilweil Gad,
- Hubbard III GeorgeBaker,
- Hwang Jeong-Min,
- Jaumendreu Urquijo Laia,
- Jurkute Neringa,
- Karanjia Rustum,
- Khemliche Wahiba,
- La Morgia Chiara,
- P Leroy Bart,
- Massini Maria,
- Mathias Marc,
- A Memon Muhammad,
- Mohamed Susan,
- L Moster Mark,
- J Muñoz NegreteFrancisco,
- J Newman Nancy,
- O’Keefe Ghazala,
- Patel Shriji,
- Pecen Paula,
- H Peragallo Jason,
- Plaine Lise,
- Preston Mary,
- Rebolleda Fernández Gema,
- Romagnoli Martina,
- A Sadun Alfredo,
- A Sahel José,
- SantaMaria Melissa,
- C Sergott Robert,
- S Subramanian Prem,
- Sun Chuanbin,
- Tai Katy,
- Tollis Heather,
- Tsui Irena,
- R Tucker William,
- Vignal-Clermont Catherine,
- Wang An-Guor,
- Wilkins Saige,
- Yu-Wai-Man Patrick
Affiliations
- Nancy J Newman
- Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, Georgia, USA
- Valérie Biousse
- Ophthalmology and Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
- José-Alain Sahel
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Patrick Yu-Wai-Man
- Cambridge Eye Unit, Addenbrooke`s Hospital, Cambridge, UK
- Sean Donahue
- Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Nashville, Tennessee, USA
- Gema Rebolleda
- Ramon y Cajal University Hospital, Madrid, Spain
- Prem S Subramanian
- Ophthalmology, University of Colorado, Aurora, Colorado, USA
- Bart P Leroy
- Ophthalmology and Center for Medical Genetics, University Hospital Ghent, Gent, Belgium
- Alfredo A Sadun
- Ophthalmology, University of California David Geffen School of Medicine, Los Angeles, California, USA
- Robert C Sergott
- Neurology and Ophthalmology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
- Catherine Vignal-Clermont
- Neuro Ophthalmology and Emergencies, The Fondation Adolphe de Rothschild Hospital, Paris, France
- Bart K Chwalisz
- Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA
- Mark Moster
- Neurology and Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, USA
- An-Guor Wang
- Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
- Valerio Carelli
- Programma di Neurogenetica, IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy
- Rudrani Banik
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Fabienne Bazin
- Statistics, eXYSTAT, Malakoff, France
- Eric Cox
- GenSight Biologics SA, Paris, France
- Michel Roux
- GenSight Biologics SA, Paris, France
- Magali Taiel
- GenSight Biologics SA, PARIS, France
- Amore Giulia
- Anand Shweta
- Banik Rudrani
- Barboni Piero
- Biousse Valérie
- Boston Hayley
- Burale Asma
- Carbonelli Michele
- Carelli Valerio
- Chen Celia
- Cheng Hui-Chen
- Cho Steve
- K Chwalisz Bart
- Contin Manuela
- D’Agati Pietro
- A DeBusk Adam
- De Zaeytijd Julie
- Dobbs Jannah
- P Donahue Sean
- DuBois Lindreth
- Esposti Simona
- Fernandes Filho Alcides
- Fortin Elizabeth
- Gangaputra Sapna
- Gibbs Deborah
- Girmens Jean François
- Hage Rabih
- A Haller Julia
- Heilweil Gad
- Hubbard III GeorgeBaker
- Hwang Jeong-Min
- Jaumendreu Urquijo Laia
- Jurkute Neringa
- Karanjia Rustum
- Khemliche Wahiba
- La Morgia Chiara
- P Leroy Bart
- Massini Maria
- Mathias Marc
- A Memon Muhammad
- Mohamed Susan
- L Moster Mark
- J Muñoz NegreteFrancisco
- J Newman Nancy
- O’Keefe Ghazala
- Patel Shriji
- Pecen Paula
- H Peragallo Jason
- Plaine Lise
- Preston Mary
- Rebolleda Fernández Gema
- Romagnoli Martina
- A Sadun Alfredo
- A Sahel José
- SantaMaria Melissa
- C Sergott Robert
- S Subramanian Prem
- Sun Chuanbin
- Tai Katy
- Tollis Heather
- Tsui Irena
- R Tucker William
- Vignal-Clermont Catherine
- Wang An-Guor
- Wilkins Saige
- Yu-Wai-Man Patrick
- DOI
- https://doi.org/10.1136/bmjophth-2022-001158
- Journal volume & issue
-
Vol. 7,
no. 1
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.
