RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Diabetic Retinopathy (DR) Without Center Involved-Diabetic Macular Edema (CI-DME)
- Conditions
- Diabetic Retinopathy (DR)
- Interventions
- Genetic: RGX-314 Dose 1Genetic: RGX-314 Dose 2Genetic: RGX-314 Dose 3Drug: Topical Steroid
- Registration Number
- NCT04567550
- Lead Sponsor
- AbbVie
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RGX-314 Treatment Arm (Dose 1) RGX-314 Dose 1 RGX-314 Dose 1 RGX-314 Treatment Arm (Dose 2) RGX-314 Dose 2 RGX-314 Dose 2 RGX-314 Treatment Arm (Dose 3) and Topical Steroid RGX-314 Dose 3 RGX-314 Dose 3 and Topical Steroid RGX-314 Treatment Arm (Dose 3) and Topical Steroid Topical Steroid RGX-314 Dose 3 and Topical Steroid
- Primary Outcome Measures
Name Time Method 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 48 weeks 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.
- Secondary Outcome Measures
Name Time Method To evaluate the effect of RGX-314 on DR (ETDRS-DRSS) over time 48 weeks Proportion of participants achieving improvement or worsening in DR per ETDRS-DRSS grading through week 48
To assess the safety and tolerability of RGX-314 48 weeks Assess the incidence of overall and ocular Adverse Events (AEs)
To evaluate the need for additional Standard of Care (SOC) intervention due to ocular vision-threatening diabetic complications 48 weeks Proportion of participants with sight-threatening ocular diabetic complications requiring additional SOC intervention (anti-VEGF, Pan-Retinal Photocoagulation (PRP), laser, steroids, or surgical intervention)
To evaluate the incidences of ocular inflammation following SCS RGX-314 administration 48 weeks Proportion of participants who experience ocular inflammation following SCS RGX-314 administration.
Trial Locations
- Locations (20)
Cumberland Valley Retina Consultants
🇺🇸Hagerstown, Maryland, United States
Vision Research Center Eye Associates of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Northern California Retina Vitreous Associates Medical Group, Inc.
🇺🇸Mountain View, California, United States
Southeast Retina Center, PC
🇺🇸Augusta, Georgia, United States
Wilmer Eye Institute/Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
University Retina and Macula Associates, PC
🇺🇸Oak Forest, Illinois, United States
Mid Atlantic Retina
🇺🇸Philadelphia, Pennsylvania, United States
Retinal Research Institute, LLC
🇺🇸Phoenix, Arizona, United States
California Retina Consultants
🇺🇸Santa Barbara, California, United States
Retinal Diagnostic Center
🇺🇸Campbell, California, United States
California Eye Specialists Medical Group, Inc
🇺🇸Pasadena, California, United States
Duke University Eye Center
🇺🇸Durham, North Carolina, United States
Charles Retina Institute, P.C.
🇺🇸Germantown, Tennessee, United States
Retinal Consultants San Diego
🇺🇸Poway, California, United States
Austin Clinical Research, LLC
🇺🇸Austin, Texas, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Retinal Consultants of Texas
🇺🇸The Woodlands, Texas, United States
NJ Retina
🇺🇸Teaneck, New Jersey, United States