Phase 2
N=42
Safety and Tolerability of RGX-314 (Investigational Product) Gene Therapy for Neovascular AMD Trial
Neovascular Age-related Macular Degeneration · Wet Age-related Macular Degeneration
Bottom Line
View on ClinicalTrials.gov: NCT03066258 ↗Enrolled (actual)
42
Serious AEs
28.6%
Results posted
May 2023
Primary outcome: Primary: Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)) — 6; 6; 6; 12 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- RGX-314 (Genetic)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- REGENXBIO Inc.
- Primary completion
- Nov 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)) |
6; 6; 6; 12; 12 | — |
| SECONDARY Safety (Participants With Ocular and Non-ocular AEs and SAEs) |
6; 6; 6; 12; 12 | — |
| SECONDARY Change From Baseline in BCVA (Best Corrected Visual Acuity) |
-7.6; 1.2; 14.0; 0.9; -3.8 | — |
| SECONDARY Change From Baseline in CRT (Central Retinal Thickness) |
-88.6; 25.3; 2.0; -56.7; -108.2 | — |
| SECONDARY Supplemental Injections (Annualized Rate of Supplemental Injections) |
10.3; 9.3; 2.8; 4.4; 2.0 | — |
| SECONDARY Mean Change From Baseline in Area of CNV (Choroidal Neovascularization) |
-0.4; 0.0; -1.2; -1.1; -0.6 | — |
Summary
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.
Eligibility Criteria
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) 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.
Data sourced from ClinicalTrials.gov (NCT03066258). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.