Gene Therapy Trial for LCA2 OPTIRPE65 (AAV2/5-OPTIRPE65)
Research type
Research Study
Full title
An Open-label, Multi-centre, Phase I/II Dose Escalation Trial of an Adeno-Associated Virus Vector (AAV2/5-OPTIRPE65) for Gene Therapy of Adults and Children with Retinal Dystrophy associated with Defects in RPE65 (LCA2)
IRAS ID
187314
Contact name
James Bainbridge
Contact email
Sponsor organisation
MeiraGTx UK II Ltd
Eudract number
2015-003418-25
Duration of Study in the UK
2 years, 1 months, 1 days
Research summary
Inherited defects in the gene encoding RPE65 cause night blindness and progressive impairment of sight in children. There is currently no approved treatment available. We and others have previously demonstrated proof-of-principle for RPE65 gene therapy by delivering a modified virus vector containing a normal copy of the gene into the retina using animal models of disease and in 3 previous clinical trials. In all 3 trials, a subset of participants benefited with improved vision to varying extents during the first year, however long-term follow-up demonstrated that progressive degeneration continued unabated, and maximal improvements in retinal sensitivity were not maintained.
Further studies showed that expression of RPE65 in humans is greater than in animal models of disease, supporting the hypothesis that the continued degeneration observed in previous trials is due to insufficient RPE65 expression levels in the human retina. To increase RPE65 availability for affected humans we have developed a new optimized vector that expresses significantly greater levels of RPE65. The aim of this study is to determine the safety of the new optimized vector in humans and to explore its potential efficacy.
We will enroll LCA patients with defects in RPE65 in this study. Successful completion of the trial will be defined as acceptable safety of the vector, and evidence of benefit to sight associated with measurable improvement in the electrical function of the retina. We will also investigate evidence of protection against sight-loss in the longer term. Participants in the study will be followed for 6 months after introducing the new vector to the eye, and will subsequently be invited to enrol in a separate long-term follow-up study. We expect the results of this study to benefit those who are working on gene therapy to treat other retinal degenerations as well as diseases of other organ systems.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
16/LO/0126
Date of REC Opinion
29 Mar 2016
REC opinion
Further Information Favourable Opinion