Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
Inherited Retinal Dystrophy Due to RPE65 Mutations
Leber Congenital Amaurosis
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis (LCA) Using Adeno-Associated Viral Vector to Deliver the Gene for Human RPE65 to the Retinal Pigment Epithelium (RPE) [AAV2-hRPE65v2-301]|
- Mobility testing [ Time Frame: One year ]
- Additional visual/retinal function tests [ Time Frame: One year ]
- Ophthalmic exams, physical exams, immunology studies, clinical labs, & adverse event recording [ Time Frame: Two years ]
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||July 2029|
|Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Subretinal administration of gene therapy vector AAV2-hRPE65v2 (1.5E11 vector genomes per eye) to both eyes via surgical procedures on separate days.
Other Name: gene therapy vector
|No Intervention: Control|
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 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). Clinical diagnosis is made by function tests of the eye. This can be confirmed by a special method of testing (molecular testing) to verify that the RPE65 is not correct.
This study uses a gene therapy vector made from an adeno-associated virus (AAV) called AAV2-hRPE65v2. 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 getting the normal human RPE65 gene into the cells of the retina. An earlier 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 clinical study tested three doses of the vector in twelve children and adults. The three doses were safe for the eye and the rest of the body in individuals as young as eight years old. AAV2-hRPE65v2 administration also led to increased vision in the subjects, with the youngest subjects showing the most improvement.
This study will deliver AAV2-hRPE65v2 vector 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 effectiveness and safety of the AAV2-hRPE65v2 gene therapy vector as a possible treatment for LCA2. 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00999609
|United States, Iowa|
|University of Iowa|
|Iowa City, Iowa, United States, 52242|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Albert M Maguire, MD||Children's Hospital of Philadelphia|
|Principal Investigator:||Stephen R Russell, MD||University of Iowa|