RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Diabetic Retinopathy (DR) Without Center Involved-Diabetic Macular Edema (CI-DME) (ALTITUDE)

RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Diabetic Retinopathy (DR) Without Center Involved-Diabetic Macular Edema (CI-DME)

A Phase 2, Randomized, Dose-escalation, Observation-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of RGX-314 Gene Therapy Delivered Via a Single Suprachoroidal Space (SCS) Injections in Participants With Diabetic Retinopathy (DR) Without Center Involved-Diabetic Macular Edema (CI-DME)(ALTITUDE)

RGX-314 is being developed as a novel, potential one-time gene therapy treatment for the treatment of diabetic retinopathy, a chronic and progressive complication of diabetes mellitus. Diabetic retinopathy (DR) is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that leads to further deterioration of functional vision. Despite the availability of current treatments, diabetic retinopathy remains the leading cause of vision loss in working-age adults, those between the ages of 20 and 74. Existing treatment with anti-VEGF agents, although shown to be effective, are limited by short therapeutic half-lives, which then require frequent intravitreal injections over the patient's lifetime, resulting in increased risk of associated adverse events and significant treatment burden. Due to the burden of treatment, patients often do not closely adhere to treatment regimens and experience sub-optimal outcomes and a decline in vision. RGX-314 is being developed as a potential one time treatment for diabetic retinopathy, which may deliver advantages over conventional treatments, such as potentially providing a longer duration of therapeutic effect and intervening at an earlier stage of the disease.

This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of RGX-314 gene therapy in subjects with DR without center-involved diabetic macular edema (CI-DME). Approximately 100 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 5 cohorts. Participants will be randomized in Cohorts 1, 2, 4 and 5 to receive RGX-314 or to be observed, and participants enrolled in Cohorts 3 will receive RGX-314. Cohort 1 will evaluate RGX-314 Dose 1, Cohorts 2 and 3 will evaluate RGX-314 Dose 2, Cohorts 4 and 5 will evaluate RGX-314 Dose 3. Following SCS RGX-314 administration, participants in Cohorts 4 and 5 will receive a protocol-mandated post-procedure steroid regimen for 7 weeks. Participants who are randomized to be observed in Cohorts 1, 2, 4 and 5 will be offered RGX-314 after completing the study. Efficacy will be the primary focus of the study. Participants will be evaluated for safety and tolerability of RGX-314 throughout the study.

To evaluate the effect of RGX-314 on DR by the Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (-DRSS) at week 48

Proportion of participants achieving a 2-step or greater improvement in DR by Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (-DRSS) at Week 48 scored from Levels 10-85 with higher levels indicating greater DR severity.

Proportion of participants achieving improvement or worsening in DR per ETDRS-DRSS grading through week 48

To evaluate the need for additional Standard of Care (SOC) intervention due to ocular vision-threatening diabetic complications

Proportion of participants with sight-threatening ocular diabetic complications requiring additional SOC intervention (anti-VEGF, Pan-Retinal Photocoagulation (PRP), laser, steroids, or surgical intervention)

Inclusion Criteria: Patients 25-89 years of age with a diabetic retinopathy diagnosis of nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) secondary to diabetes mellitus Type 1 or 2 for which PRP or anti-VEGF injections can be safely deferred for at least 6 months Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better) Prior history of CI-DME in the study eye is acceptable. Must be willing and able to provide written, signed informed consent. Exclusion Criteria: Neovascularization in the study eye from a cause other than DR. Presence of any active CI-DME. Active or history of retinal detachment in the study eye. Any evidence or documented history of PRP or retinal laser in the study eye. Patients who had a prior vitrectomy surgery. Women of childbearing potential. Note: Other inclusions/exclusions criteria apply