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

NCT ID: NCT04567550

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 139 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-20
• Study Completion Date: 2026-12-31

Brief Summary

ABBV-RGX-314 is being developed as a novel, potential one-time gene therapy treatment for the treatment of Diabetic Retinopathy (DR) with and without Center-Involved Diabetic Macular Edema (CI-DME). DR is a chronic and progressive complication of diabetes mellitus. It 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.

Detailed Description

This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of ABBV-RGX-314 gene therapy in subjects with DR with and without center-involved diabetic macular edema (CI-DME).

Part 1: For subjects with DR without 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 ABBV-RGX-314 or to be observed, and participants enrolled in Cohort 3 will receive ABBV-RGX-314. Cohort 1 will evaluate ABBV-RGX-314 Dose 1, Cohorts 2 and 3 will evaluate ABBV-RGX-314 Dose 2, and Cohorts 4 and 5 will evaluate ABBV-RGX-314 Dose 3. Following SCS ABBV-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 ABBV-RGX-314 after completing the study.

Part 2: For subjects with DR with CI-DME, approximately 30 participants who meet the inclusion/exclusion criteria will be enrolled into one cohort (Cohort A). Participants will be randomized to receive ABBV-RGX-314 or Aflibercept Control. Cohort A will evaluate ABBV-RGX-314 Dose 4. Participants randomized to receive SCS ABBV-RGX-314 will receive a protocol-mandated course of steroid. Participants who are randomized to the Aflibercept Control arm will be offered ABBV-RGX-314 after completing the study.

Conditions

Diabetic Retinopathy (DR); Center-Involved Diabetic Macular Edema (CI-DME)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Part 1: Observation Control Arm

Observation Control

Group Type: NO_INTERVENTION

No interventions assigned to this group

Part 1: ABBV-RGX-314 Treatment Arm (Dose 1)

ABBV-RGX-314 Dose 1

Group Type: EXPERIMENTAL

ABBV-RGX-314 Dose 1

Intervention Type: GENETIC

AAV8 vector containing a transgene for anti-VEGF fab (Dose 1)

Part 1: ABBV-RGX-314 Treatment Arm (Dose 2)

ABBV-RGX-314 Dose 2

Group Type: EXPERIMENTAL

ABBV-RGX-314 Dose 2

Intervention Type: GENETIC

AAV8 vector containing a transgene for anti-VEGF fab (Dose 2)

Part 1: ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid

ABBV-RGX-314 Dose 3 and Topical Steroid

Group Type: EXPERIMENTAL

ABBV-RGX-314 Dose 3

Intervention Type: GENETIC

AAV8 vector containing a transgene for anti-VEGF fab (Dose 3)

Topical Steroid

Intervention Type: DRUG

Topical Steroid

Part 2: ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid

ABBV-RGX-314 Dose 4 and Topical Steroid

Group Type: EXPERIMENTAL

Topical Steroid

Intervention Type: DRUG

Topical Steroid

ABBV-RGX-314 Dose 4

Intervention Type: GENETIC

AAV8 vector containing a transgene for anti-VEGF fab (Dose 4)

Part 2: Aflibercept Control

Control treatment arm

Group Type: ACTIVE_COMPARATOR

Aflibercept

Intervention Type: BIOLOGICAL

Aflibercept

Interventions

ABBV-RGX-314 Dose 1

AAV8 vector containing a transgene for anti-VEGF fab (Dose 1)

Intervention Type: GENETIC

ABBV-RGX-314 Dose 2

AAV8 vector containing a transgene for anti-VEGF fab (Dose 2)

Intervention Type: GENETIC

ABBV-RGX-314 Dose 3

AAV8 vector containing a transgene for anti-VEGF fab (Dose 3)

Intervention Type: GENETIC

Topical Steroid

Topical Steroid

Intervention Type: DRUG

ABBV-RGX-314 Dose 4

AAV8 vector containing a transgene for anti-VEGF fab (Dose 4)

Intervention Type: GENETIC

Aflibercept

Aflibercept

Intervention Type: BIOLOGICAL

Other Intervention Names

Genetic/ Combination Product; Genetic/ Combination Product; Genetic/ Combination Product; Genetic/ Combination Product

Eligibility Criteria

Inclusion Criteria

• Patients 25-89 years of age with a diabetic retinopathy (DR) 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
• HbA1c < 12%.
• 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.

• Patients 25-89 years of age with diabetic retinopathy secondary to diabetes mellitus Type 1 or 2.
• HbA1c < 12%
• Macular thickening secondary to DME involving the center of the fovea, CST on SD-OCT (≥ 325 μm)
• Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of 78-25 letters (approximate Snellen equivalent of 20/32 to 20/320)
• Participants must have demonstrated a meaningful response to anti-VEGF therapy.
• 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.

Part 2 (DR with CI-DME):

• Neovascularization in the study eye from a cause other than DR.
• 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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

REGENXBIO Inc.

INDUSTRY

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Retinal Research Institute, LLC

Phoenix, Arizona, United States

Barnet Dulaney Perkins Eye Center

Phoenix, Arizona, United States

California Retina Consultants

Bakersfield, California, United States

Retina-Vitreous Associates Medical Group

Beverly Hills, California, United States

Retinal Diagnostic Center

Campbell, California, United States

Northern California Retina Vitreous Associates Medical Group, Inc.

Mountain View, California, United States

California Eye Specialists Medical Group, Inc

Pasadena, California, United States

Retinal Consultants San Diego

Poway, California, United States

California Retina Consultants

Santa Barbara, California, United States

Southeast Retina Center, PC

Augusta, Georgia, United States

University Retina and Macula Associates, PC

Oak Forest, Illinois, United States

Springfield Clinic

Springfield, Illinois, United States

Wilmer Eye Institute/Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Cumberland Valley Retina Consultants

Hagerstown, Maryland, United States

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Sierra Eye Associates

Reno, Nevada, United States

NJ Retina

Teaneck, New Jersey, United States

Vision Research Center Eye Associates of New Mexico

Albuquerque, New Mexico, United States

Duke University Eye Center

Durham, North Carolina, United States

Mid Atlantic Retina

Philadelphia, Pennsylvania, United States

Charles Retina Institute, P.C.

Germantown, Tennessee, United States

Retina Research Institute of Texas, LLC

Abilene, Texas, United States

Austin Clinical Research, LLC

Austin, Texas, United States

Star Retina

Burleson, Texas, United States

Retinal Consultants of Texas

The Woodlands, Texas, United States

Countries

United States

Other Identifiers

RGX-314-2202 (M23-414)

Identifier Type: -

Identifier Source: org_study_id