Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis

2014-08-27 03:18:29 | BioPortfolio


This study will deliver AAV2-hRPE65v2 vector to twelve subjects, age three or older; subjects will receive the vector via subretinal injection during surgery. 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 Leber Congenital Amaurosis (LCA2).


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. LCA is incurable and untreatable and there is significantly poor vision at birth. Cells in the retina are lost over time in people with LCA which leads to total blindness. 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 twelve more subjects, age three or older; subjects will receive the vector via a subretinal injection during surgery. 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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Leber Congenital Amaurosis Due to RPE65 Mutations




University of Iowa
Iowa City
United States


Not yet recruiting


Children's Hospital of Philadelphia

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:18:29-0400

Clinical Trials [632 Associated Clinical Trials listed on BioPortfolio]

Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis

The purpose of the study is to evaluate the safety and efficacy of an adeno-associated virus vector expressing RPE65 in patients with Leber congenital amaurosis caused by mutations in the ...

A Safety/Proof of Concept Study to Evaluate the Effects of Oral QLT091001 in Subjects With Leber Congenital Amaurosis (LCA) Due to RPE65 or LRAT Mutations

The purpose of this study is to evaluate whether 7-day treatment with oral QLT091001 is safe, tolerable and can improve visual function in subjects with Leber Congenital Amaurosis (LCA) du...

Long-Term Follow-Up Gene Therapy Study for Leber Congenital Amaurosis OPTIRPE65 (Retinal Dystrophy Associated With Defects in RPE65)

This study is a longer-term follow-up study for patients who have been administered AAV2/5-OPTIRPE65 in the Phase I/II, open label, non-randomised, two-centre, dose escalation trial in adu...

Long-term Follow-up Study in Subjects Who Received Voretigene Neparvovec-rzyl (AAV2-hRPE65v2)

Multi-site, non-randomized, observational study, for up to 15 years after subretinal AAV2-hRPE65v2 administration for each subject. The study is a non-interventional, follow-up study of su...

Natural History Study in Inherited Retinal Disease Subjects Caused by Mutations in RPE65 or LRAT

To evaluate the natural history of visual function in subjects with IRD phenotypically diagnosed as Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP) caused by RPE65 or LRAT ge...

PubMed Articles [4223 Associated PubMed Articles listed on BioPortfolio]

A Cross-Sectional and Longitudinal Study of Retinal Sensitivity in RPE65-Associated Leber Congenital Amaurosis.

RPE65-associated Leber congenital amaurosis (RPE65-LCA) is an early-onset severe retinal dystrophy associated with progressive visual field loss. Phase I/II and III gene therapy trials have identified...

Deficiency of type 2 iodothyronine deiodinase reduces necroptosis activity and oxidative stress responses in retinas of Leber congenital amaurosis model mice.

Thyroid hormone (TH) signaling has been shown to regulate cone photoreceptor viability. Suppression of TH signaling with antithyroid drug treatment or by targeting iodothyronine deiodinases and TH rec...

Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA.

Ocular gene therapy with recombinant adeno-associated virus (AAV) has shown vector-mediated gene augmentation to be safe and efficacious in the retina in one set of diseases (retinitis pigmentosa and ...

Generation of a human iPSC line from a patient with Leber congenital amaurosis caused by mutation in AIPL1.

The human induced pluripotent stem cell (hiPSC) line, derived from dermal fibroblasts from Leber congenital amaurosis patient with homozygous mutation c.265 T > C, p.Cys89Arg in aryl hydrocarbon...

Parapapillary Optic Nerve Head Drusen in Leber Congenital Amaurosis.

A 20-year-old male who was known to have Leber congenital amaurosis was assessed. Best-corrected visual acuity was counting fingers in both eyes (OU). Anterior segment OU revealed poorly reacting pupi...

Medical and Biotech [MESH] Definitions

A rare degenerative inherited eye disease that appears at birth or in the first few months of life that results in a loss of vision. Not to be confused with LEBER HEREDITARY OPTIC NEUROPATHY, the disease is thought to be caused by abnormal development of PHOTORECEPTOR CELLS in the RETINA, or by the extremely premature degeneration of retinal cells.

A maternally linked genetic disorder that presents in mid-life as acute or subacute central vision loss leading to central scotoma and blindness. The disease has been associated with missense mutations in the mtDNA, in genes for Complex I, III, and IV polypeptides, that can act autonomously or in association with each other to cause the disease. (from Online Mendelian Inheritance in Man,, MIM#535000 (April 17, 2001))

Hereditary conditions that feature progressive visual loss in association with optic atrophy. Relatively common forms include autosomal dominant optic atrophy (OPTIC ATROPHY, AUTOSOMAL DOMINANT) and Leber hereditary optic atrophy (OPTIC ATROPHY, HEREDITARY, LEBER).

Rare congenital lymphoid disorder due to mutations in certain Fas-Fas ligand pathway genes. Known causes include mutations in FAS, TNFSF6, NRAS, CASP8, and CASP10 proteins. Clinical features include LYMPHADENOPATHY; SPLENOMEGALY; and AUTOIMMUNITY.

A heterogeneous group of disorders characterized by a congenital defect in neuromuscular transmission at the NEUROMUSCULAR JUNCTION. This includes presynaptic, synaptic, and postsynaptic disorders (that are not of autoimmune origin). The majority of these diseases are caused by mutations of various subunits of the nicotinic acetylcholine receptor (RECEPTORS, NICOTINIC) on the postsynaptic surface of the junction. (From Arch Neurol 1999 Feb;56(2):163-7)

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