Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD

Study Overview
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Brief Summary
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RGX-314 is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to 12 weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time. RGX-314 is being developed as a potential one-time treatment for wet AMD.

Detailed Description
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This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of RGX-314 gene therapy in participants with nAMD. The study will evaluate 2 dose levels of RGX-314 gene therapy relative to an active comparator. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of RGX-314 relative to aflibercept. Approximately 465 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.

Official Title
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A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD

Conditions
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AMD, wAMD, nAMD, Wet Age-related Macular Degeneration, WetAMD, CNV

Intervention / Treatment
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* Genetic: RGX-314 Dose 1
* Genetic: RGX-314 Dose 2
* Biological: Aflibercept (EYLEA®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 50 years and ≤ 89 years An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye Diagnosis of subfoveal CNV secondary to AMD in the study eye previously treated with anti-VEGF Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye. Willing and able to provide written, signed informed consent for this study Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry Exclusion Criteria: CNV or macular edema in the study eye secondary to any causes other than AMD Subfoveal fibrosis or atrophy in the study eye Any condition in the investigator's opinion that could limit VA improvement in the study eye Active or history of retinal detachment or current retinal tear in the study eye Advanced glaucoma or history of secondary glaucoma in the study eye Myocardial infarction, cerebrovascular accident, or transient ischemic attach within the past 6 months. History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1 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 Visit 1. Prior treatment with gene therapy.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 89 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 RGX-314 treatment arms, 1 control arm (aflibercept)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RGX-314 Dose 1<br>RGX-314 Dose 1 administered via subretinal delivery one time. | Genetic: RGX-314 Dose 1<br>* AAV8 vector containing a transgene for anti-VEGF Fab (Dose 1)<br>|
| Experimental: RGX-314 Dose 2<br>RGX-314 Dose 2 administered via subretinal delivery one time. | Genetic: RGX-314 Dose 2<br>* AAV8 vector containing a transgene for anti-VEGF Fab (Dose 2)<br>|
| Active Comparator: Control Arm<br>Aflibercept administered via intravitreal injection approximately every 8 weeks | Biological: Aflibercept (EYLEA®)<br>* 2.0 mg (0.05 mLsolution) administered by intravitreal injection approximately every 8 weeks after 3 monthly injections Other Names: • Eylea (anti-VEGF agent)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in Best Corrected Visual Acuity (BCVA) | BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS) | At Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidences of ocular and overall Serious Adverse Events (SAEs) | Incidences of ocular and overall Serious Adverse Events | At Week 54 | 
| Mean change from baseline in BCVA | BCVA measured by ETDRS | At Week 54 (RGX-314 randomized participants only) | 
| Mean change from baseline in CRT and CPT as measured by SD-OCT | CRT and CPT as measured by SD-OCT | At Week 54 and Week 90 | 
| Mean reduction in supplemental anti VEGF injection annualized rate compared with the prior year of therapy | Supplemental anti-VEGF treatments required post therapy to the year prior | Through Week 54 and Week 108 | 
| Mean supplemental anti VEGF injection annualized rate in the RGX-314 arms | Supplemental anti-VEGF treatments required post therapy to the year prior | Through Week 54 and Week 108 | 
| Aqueous RGX-314 TP concentrations | Observation of concentration of RGX-314 in the aqueous humor over time | At Week 14, Week 38, Week 54, Week 74, Week 90 and Week 108 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-Related Macular Degeneration, Neovascular Age-Related Macular Degeneration, Macular Degeneration, Wet Macular Degeneration, Choroidal Neovascularization, Retinal Degeneration, Retinal Diseases, Eye Diseases, Ranibizumab, Aflibercept, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors, Antineoplastic Agents, Gene Therapy, Anti-vascular endothelial grown factory therapy, Anti-VEGF therapy