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 [581 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...

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...

Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA)

The inherited retinal dystrophies are a clinically and genetically heterogeneous group of conditions, which often present in childhood.Inherited retinal degenerations cause sight impairmen...

PubMed Articles [4206 Associated PubMed Articles listed on BioPortfolio]

Amaurosis congénita de Leber RPE-65, seguimiento a 7 años.

Leber congenital amaurosis is a retinal dystrophy with several forms of presentation due to its genetic variability. Case of a female girl followed up from 4 to 11 years old is presented, with positiv...

Severe Loss of Tritan Color Discrimination in RPE65 Associated Leber Congenital Amaurosis.

RPE65-associated Leber congenital amaurosis (RPE65-LCA) is a progressive severe retinal dystrophy with early profound dysfunction of rod photoreceptors followed by progressive cone photoreceptor degen...

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...

The genetic profile of Leber congenital amaurosis in an Australian cohort.

Leber congenital amaurosis (LCA) is a severe visual impairment responsible for infantile blindness, representing ~5% of all inherited retinal dystrophies. LCA encompasses a group of heterogeneous diso...

Gene therapy and genome surgery in the retina.

Precision medicine seeks to treat disease with molecular specificity. Advances in genome sequence analysis, gene delivery, and genome surgery have allowed clinician-scientists to treat genetic conditi...

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))

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.

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).

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)

More From BioPortfolio on "Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis"

Quick Search


Relevant Topics

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

DNA sequencing
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...

Searches Linking to this Trial