Long-term Follow-Up Study of RGX-314 and Fellow Eye Substudy

Study Overview
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Brief Summary
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This is a prospective, observational study designed to evaluate the long-term safety and efficacy of RGX-314. Eligible participants are those who were previously enrolled in a clinical study in which they received a single subretinal administration of RGX-314 in their study eye. Enrollment of each participant in the current study should occur after the participant has completed either the end of study or early termination visit in the previous (parent) clinical study. Participants will be followed for up to 5 years post-RGX-314 administration (inclusive of the parent study). After enrollment and a 6-month follow-up visit, participants will attend at least annual study visits through the end of the 5-year post-RGX-314 administration follow-up period. Additionally, an interventional fellow eye treatment substudy will evaluate the safety, efficacy, and immunogenicity of subretinal RGX-314 administration in the fellow eye of participants having bilateral disease who previously received a subretinal injection of RGX-314 in their study eye. Participants who qualify for the substudy will receive subretinal administration of RGX-314 in their fellow eye and complete 13 study visits in a 54-week period. Following completion of the substudy participants will continue in the observational portion of the study for up to 5 years post RGX-314 administration in their fellow eye.

Official Title
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A Long-term Follow-Up Study to Evaluate the Safety and Efficacy of RGX-314 Following Subretinal Administration in Participants With Neovascular Age-related Macular Degeneration and Fellow Eye Treatment Substudy

Conditions
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Neovascular Age-related Macular Degeneration, Wet Macular Degeneration

Intervention / Treatment
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* Genetic: RGX-314


Participation Criteria
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Eligibility Criteria
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Main Observational Study: Inclusion Criteria: Able and willing to provide written consent Previously enrolled in a clinical study of RGX-314 and received a single subretinal administration of RGX-314 Exclusions Criteria: 1. None Fellow Eye Substudy: Inclusion Criteria Age ≤ 93 years Currently or previously enrolled in the main observational study Diagnosis of bilateral choroidal neovascularization secondary to age-related macular degeneration Active nAMD in the fellow eye BCVA between ≤ 80 and ≥ 20 letters in the fellow eye Exclusion Criteria: CNV or macular edema in the fellow eye secondary to causes other than nAMD Subfoveal fibrosis or atrophy in the fellow eye Advanced glaucoma or history of secondary glaucoma in the fellow eye or any invasive procedure to treat glaucoma Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months History of intraocular surgery in the fellow eye within 12 weeks of screening History of intravitreal therapy, such as intravitreal steroid injection or investigational product, other than an intravitreal therapy for nAMD, in the fellow eye within 6 months of screening

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: 1 main Observational study arm, 1 RGX-314 Fellow Eye Treatment substudy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Main Observational Study<br>All subjects that previously received RGX-314 in a subretinal administration parent study are enrolled into this arm. | |
| Experimental: RGX-314 Fellow Eye Treatment Substudy<br>RGX-314 Fellow Eye Treatment | Genetic: RGX-314<br>* AAV8 vector containing a transgene for anti-VEGF Fab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of ocular adverse events and any serious adverse events in the study eye |  | 5 years inclusive of parent study | 
| Fellow eye substudy: Incidence of ocular adverse events and any serious adverse events in the fellow eye |  | 54 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in best corrected visual acuity (BCVA) in the study eye | Mean change and proportion of participants losing greater than or equal to 5, 10, and 15 letters | 5 years inclusive of parent study | 
| Change from baseline in Central Retinal Thickness (CRT) in the study eye | Mean change from baseline in CRT as measured by spectral domain optical coherence tomography (SD-OCT) | 5 years inclusive of parent study | 
| Number of supplemental anti-VEGF injections in the study eye | Mean number of supplemental anti-VEGF injections based on chart review | 5 years inclusive of parent study | 
| Number of retinal specialist visits for the study eye | Mean number of retinal specialist visits attended for nAMD based on chart review | 5 years inclusive of parent study | 
| Fellow eye substudy: Change from baseline in best corrected visual acuity | Mean change from baseline in BCVA in the fellow eye | 54 weeks | 
| Fellow eye substudy: Change from baseline in Central Retinal Thickness in the fellow eye | Mean change from baseline in CRT in the fellow eye as measured by SD-OCT | 54 weeks | 
| Fellow eye substudy: Number of supplemental anti-VEGF injections in the fellow eye | Mean number of supplemental anti-VEGF injections in the fellow eye | 54 weeks | 
| Fellow eye substudy: Aqueous and Serum RGX-314 transgene product (TP) concentrations in the fellow eye | Fellow eye aqueous and serum RGX-314 TP concentrations at assessed time points | 54 weeks | 
| Fellow eye substudy: Immunogenicity measurements in the fellow eye | Fellow eye immunogenicity measurements at assessed timepoints | 54 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gene therapy, wet AMD, nAMD