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)

NCT04567550 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: RGX-314-2202 (M23-414)
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 25

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.

Conditions

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

Keywords

DR; CI-DME

Outcome Measures

Primary Outcomes (2)

• Part 1: Proportion of participants achieving a 2-step or greater improvement in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography at Week 48

  To evaluate the effect of ABBV-RGX-314 on DR by the ETDRS DRSS at Week 48.

  At Week 48

• Part 2: Mean change from baseline in Best Corrected Visual Acuity (BCVA) in the study eye at Week 54.

  To evaluate the effect of ABBV-RGX-314 on BCVA at Week 54.

  At Week 54

Secondary Outcomes (39)

• Part 1: Proportion of participants achieving an improvement in DR in the study eye per the ETDRS DRSS on 4 widefield digital stereoscopic fundus photography.

  At Week 4, Week 12, Week 24, and Week 36

• Part 1:Proportion of participants achieving a 0-step (no change) or greater improvement in DR in the study eye per the ETDRS DRSS on 4 widefield digital stereoscopic fundus photography.

  At Week 4, Week 12, Week 24, Week 36, and Week 48

• Part 1:Proportion of participants with a worsening in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography.

  At Week 4, Week 12, Week 24, Week 36, and Week 48

• Part 1: Proportion of participants in the NPDR and PDR subgroups at baseline achieving an improvement or worsening in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography.

  At Week 4, Week 12, Week 24, Week 36, and Week 48

• Part 1: Proportion of participants graded as proliferative diabetic retinopathy (PDR) in the study eye at baseline achieving regression to nonproliferative diabetic retinopathy (NPDR) in the study eye.

  At Week 24, Week 36, and Week 48

Study Arms (6)

Part 1: Observation Control Arm

NO INTERVENTION

Observation Control

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

EXPERIMENTAL

ABBV-RGX-314 Dose 1

Genetic: ABBV-RGX-314 Dose 1

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

EXPERIMENTAL

ABBV-RGX-314 Dose 2

Genetic: ABBV-RGX-314 Dose 2

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

EXPERIMENTAL

ABBV-RGX-314 Dose 3 and Topical Steroid

Genetic: ABBV-RGX-314 Dose 3; Drug: Topical Steroid

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

EXPERIMENTAL

ABBV-RGX-314 Dose 4 and Topical Steroid

Drug: Topical Steroid; Genetic: ABBV-RGX-314 Dose 4

Part 2: Aflibercept Control

ACTIVE COMPARATOR

Control treatment arm

Biological: Aflibercept

Interventions

ABBV-RGX-314 Dose 1 GENETIC

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

Also known as: Genetic/ Combination Product

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

ABBV-RGX-314 Dose 2 GENETIC

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

Also known as: Genetic/ Combination Product

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

ABBV-RGX-314 Dose 3 GENETIC

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

Also known as: Genetic/ Combination Product

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

Topical Steroid DRUG

Topical Steroid

Part 1: ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid; Part 2: ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid

ABBV-RGX-314 Dose 4 GENETIC

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

Also known as: Genetic/ Combination Product

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

Aflibercept BIOLOGICAL

Aflibercept

Part 2: Aflibercept Control

Eligibility Criteria

• Age: 25 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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):
• 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
• Neovascularization in the study eye from a cause other than DR.
• Active or history of retinal detachment in the study eye.

Sponsors & Collaborators

• AbbVie: lead
• REGENXBIO Inc.: collaborator

Study Sites (25)

Retinal Research Institute, LLC

Phoenix, Arizona, 85014, United States

Location

Barnet Dulaney Perkins Eye Center

Phoenix, Arizona, 85016, United States

Location

California Retina Consultants

Bakersfield, California, 93309, United States

Location

Retina-Vitreous Associates Medical Group

Beverly Hills, California, 90017, United States

Location

Retinal Diagnostic Center

Campbell, California, 95008, United States

Location

Northern California Retina Vitreous Associates Medical Group, Inc.

Mountain View, California, 94040, United States

Location

California Eye Specialists Medical Group, Inc

Pasadena, California, 91107, United States

Location

Retinal Consultants San Diego

Poway, California, 92064, United States

Location

California Retina Consultants

Santa Barbara, California, 93103, United States

Location

Southeast Retina Center, PC

Augusta, Georgia, 30909, United States

Location

University Retina and Macula Associates, PC

Oak Forest, Illinois, 60452, United States

Location

Springfield Clinic

Springfield, Illinois, 62702, United States

Location

Wilmer Eye Institute/Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Cumberland Valley Retina Consultants

Hagerstown, Maryland, 21740, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

NJ Retina

Teaneck, New Jersey, 07666, United States

Location

Vision Research Center Eye Associates of New Mexico

Albuquerque, New Mexico, 87109, United States

Location

Duke University Eye Center

Durham, North Carolina, 27705, United States

Location

Mid Atlantic Retina

Philadelphia, Pennsylvania, 19107, United States

Location

Charles Retina Institute, P.C.

Germantown, Tennessee, 38138, United States

Location

Retina Research Institute of Texas, LLC

Abilene, Texas, 79606, United States

Location

Austin Clinical Research, LLC

Austin, Texas, 78750, United States

Location

Star Retina

Burleson, Texas, 76028, United States

Location

Retinal Consultants of Texas

The Woodlands, Texas, 77384, United States

Location

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

Steroids; aflibercept

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: September 28, 2020
• Study Start: November 20, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (25)