Excessive vascular endothelial growth factor (VEGF) plays a key part in promoting neovascularization and edema in neovascular (wet) age-related macular degeneration (nAMD). VEGF inhibitors (anti-VEGF), including ranibizumab (LUCENTIS®, Genentech) and aflibercept (EYLEA®, Regeneron), have been shown to be safe and effective for treating nAMD and have demonstrated improvement in vision. However, anti-VEGF therapy is administered frequently via intravitreal injection and can be a significant burden to the patients. RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein. The long-term, stable delivery of this therapeutic protein following a 1 time gene therapy treatment for nAMD could potentially reduce the treatment burden of currently available therapies while maintaining vision with a favorable benefit:risk profile.
This Phase I/IIa, open-label, multiple-cohort, dose-escalation study was designed to evaluate the safety and tolerability of RGX-314 gene therapy in subjects with previously treated nAMD. Five doses were studied in approximately 42 subjects. Subjects who met the inclusion/exclusion criteria and had an anatomic response to an initial anti-VEGF injection received a single dose of RGX-314 administered by subretinal delivery. RGX-314 uses an AAV8 vector that contains a gene that encodes for a monoclonal antibody fragment which binds to and neutralizes VEGF activity. Safety was the primary focus for the initial 24 weeks after RGX-314 administration (primary study period). Following completion of the primary study period, subjects continued to be assessed until 104 weeks following treatment with RGX-314.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Santa Barbara location
Santa Barbara, California, United States
Baltimore location
Baltimore, Maryland, United States
Boston location
Boston, Massachusetts, United States
Reno location
Reno, Nevada, United States
Philadelphia location 1
Philadelphia, Pennsylvania, United States
Philadelphia location 2
Philadelphia, Pennsylvania, United States
Memphis location
Germantown, Tennessee, United States
Houston location
Houston, Texas, United States
Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))
Participants with ocular and non-ocular AEs and SAEs through 26 weeks (24 weeks following RGX-314 administration)
Time frame: 26 weeks (24 weeks following RGX-314 administration)
Safety (Participants With Ocular and Non-ocular AEs and SAEs)
Participants with ocular and non-ocular AEs and SAEs
Time frame: 106 weeks (104 weeks following RGX-314 administration)
Change From Baseline in BCVA (Best Corrected Visual Acuity)
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.
Time frame: 106 weeks (104 weeks following RGX-314 administration)
Change From Baseline in CRT (Central Retinal Thickness)
Retinal fluid status of the study eye was evaluated using spectral domain OCT (Optical Coherence Tomography). A decrease in value indicates a decrease in fluid
Time frame: 106 weeks (104 weeks following RGX-314 administration)
Supplemental Injections (Annualized Rate of Supplemental Injections)
The number of supplemental anti-VEGF injections given after RGX-314 was administered. Injections per year which were determined by the number of supplemental injections divided total follow-up in study days which is annualized to a per year rate. Injections were given for signs of worsening disease at a study visit, per the discretion of the investigator.
Time frame: 106 weeks (104 weeks following RGX-314 administration)
Mean Change From Baseline in Area of CNV (Choroidal Neovascularization)
Area of Choroidal Neovascularization of the study eye was assessed with color fundus photography. Analysis was performed by the central reading center. An increase in value represents an increase in CNV.
Time frame: 106 weeks (104 weeks following RGX-314 administration)
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