Safety and Tolerability of RGX-314 (Investigational Product) Gene Therapy for Neovascular AMD Trial

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.

Inclusion criteria

• Patients ≥ 50 and ≤ 89 years with a diagnosis of subfoveal CNV (Choroidal neovascularization) secondary to AMD in the study eye receiving prior intravitreal anti-VEGF therapy.
• BCVA (Best Corrected Visual Acuity) between ≤20/63 and ≥20/400 (≤63 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/40 and ≥20/400 (≤73 and ≥19 ETDRS letters) for the rest of the cohort.
• History of need for and response to anti-VEGF therapy.
• Response to anti-VEGF at trial entry (assessed by SD-OCT (Spectral Domain Optical Coherence Tomography) at week 1)
• Must be pseudophakic (status post cataract surgery) in the study eye.
• AST (Aspartate aminotransferase)/ALT (Alanine aminotransferase) < 2.5 × ULN (Upper limit of normal); TB (Total bilirubin) < 1.5 × ULN; PT (Prothrombin time) < 1.5 × ULN; Hb > 10 g/dL (males) and > 9 g/dL (females); Platelets > 100 × 10^3/µL; eGFR (Estimated glomerular filtration rate) > 30 mL/min/1.73 m^2
• Must be willing and able to provide written, signed informed consent.

Exclusion criteria

• CNV or macular edema in the study eye secondary to any causes other than AMD.
• Any condition preventing visual acuity improvement in the study eye, eg, fibrosis, atrophy, or retinal epithelial tear in the center of the fovea.
• Active or history of retinal detachment in the study eye.
• Advanced glaucoma in the study eye.
• History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening.
• Presence of an implant in the study eye at screening (excluding intraocular lens).
• Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within the past 6 months.
• Uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100 mmHg) despite maximal medical treatment.