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)

Phase 2Active Not RecruitingNCT04567550

AbbVie139 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Interventions

ABBV-RGX-314 Dose 1GENETIC

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

ABBV-RGX-314 Dose 2GENETIC

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

ABBV-RGX-314 Dose 3GENETIC

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

Topical SteroidDRUG

Topical Steroid

ABBV-RGX-314 Dose 4GENETIC

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

AfliberceptBIOLOGICAL

Aflibercept

Eligibility

Sex: ALLMin age: 25 YearsMax age: 89 Years

Medical Language ↔ Plain English

Part 1 (DR without CI-DME): 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. 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): Inclusion Criteria: * 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. * 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.

Locations (25)

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

...and 15 more locations

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: At Week 54

Secondary Outcomes

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.