Clinical Trial: Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Pigmen

Brief Summary: The study is a Phase 3, open-label, randomized controlled trial of gene therapy intervention by subretinal administration of AAV2-hRPE65v2. At least twenty-four subjects, three years of age or older, will be recruited. The intervention group will receive AAV2-hRPE65v2 vector at either The Children's Hospital of Philadelphia or University of Iowa to determine if it improves visual and retinal function in individuals with LCA2.

Detailed Summary:

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).
Sponsor: Spark Therapeutics

Current Primary Outcome: Mobility testing [ Time Frame: One year ]

Original Primary Outcome: Pupillary light reflex (PLR)- increased sensitivity to light as evidenced by increased velocity of constriction and/or increased amplitude of constriction [ Time Frame: Six months ]

Current Secondary Outcome:

  • Additional visual/retinal function tests [ Time Frame: One year ]
  • Ophthalmic exams, physical exams, immunology studies, clinical labs, & adverse event recording [ Time Frame: Two years ]


Original Secondary Outcome:

  • Additional visual/retinal function tests and ocular motility measurements [ Time Frame: Six months ]
  • Ophthalmic exams, physical exams, immunology studies, clinical labs, & adverse event recording [ Time Frame: Six months ]


Information By: Spark Therapeutics

Dates:
Date Received: October 21, 2009
Date Started: October 2012
Date Completion: July 2029
Last Updated: March 24, 2017
Last Verified: March 2017