Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is a disease where part of the eye (the retina) is severely diseased. Usually it is detected in affected people within the first few months of life, as there is significantly poor vision at birth. Cells in the retina are lost over time in people with LCA, which typically leads to total blindness. There are no pharmacological treatments available. This study will focus on the form of LCA caused by changes (mutations) in DNA that makes a certain protein (called the 65 kDa retinal pigment epithelium (RPE)-specific protein, or RPE65). This can be confirmed by a special method of testing (molecular testing) to verify the presence of RPE65 gene mutations.

This study uses a gene therapy vector made from an adeno-associated virus (AAV) called AAV2-hRPE65v2 (voretigene neparovec-rzyl). Gene therapy refers to the incorporation of new DNA into cells with the goal of supplying a therapeutic gene or a gene that is missing or not functioning in the cell. The AAV parts of the gene therapy vector work as a delivery vehicle for providing the normal human RPE65 gene to the cells of the retina. An earlier Phase 1 clinical study of AAV2-hRPE65v2 was conducted based on the demonstration of safety and effectiveness of the vector in animals with a similar eye disease. The earlier Phase 1 clinical study was a dose-escalation study primarily designed to evaluate safety in humans, and tested three doses of the vector in twelve children and adults. The safety of injecting into the second eye was also evaluated. The results from these earlier Phase 1 studies showed an acceptable safety profile.

This study will deliver AAV2-hRPE65v2 vector (voretigene neparvovec-rzyl) to at least sixteen intervention group subjects, age three or older; subjects will receive the vector in both eyes via subretinal injections during surgeries (on separate days). The purpose of this research study is to assess the efficacy and safety of the AAV2-hRPE65v2 gene therapy vector (voretigene neparvovec-rzyl) as a possible treatment for LCA due to RPE65 gene mutations. The control group of at least eight subjects will be able to cross-over to the intervention group after one year, provided they still meet all eligibility criteria.