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) (ALTITUDE®)

A Phase 2, Randomized, Controlled, Dose-escalation 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) With and Without Center Involved-Diabetic Macular Edema (CI-DME)(ALTITUDE)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Retinopathy (DR); Center-Involved Diabetic Macular Edema (CI-DME)
• Intervention / Treatment: Drug: Topical Steroid; Genetic: ABBV-RGX-314 Dose 1; Genetic: ABBV-RGX-314 Dose 2; Genetic: ABBV-RGX-314 Dose 3; Genetic: ABBV-RGX-314 Dose 4; Biological: Aflibercept

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.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Barnet Dulaney Perkins Eye Center
    • Phoenix, Arizona, United States, 85014
      • Retinal Research Institute, LLC
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90017
      • Retina-Vitreous Associates Medical Group
    • Campbell, California, United States, 95008
      • Retinal Diagnostic Center
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates Medical Group, Inc.
    • Pasadena, California, United States, 91107
      • California Eye Specialists Medical Group, Inc
    • Poway, California, United States, 92064
      • Retinal Consultants San Diego
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center, PC
  • Illinois
    • Oak Forest, Illinois, United States, 60452
      • University Retina and Macula Associates, PC
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute/Johns Hopkins University School of Medicine
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • NJ Retina
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Vision Research Center Eye Associates of New Mexico
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Eye Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute, P.C.
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas, LLC
    • Austin, Texas, United States, 78750
      • Austin Clinical Research, LLC
    • Burleson, Texas, United States, 76028
      • Star Retina
    • The Woodlands, Texas, United States, 77384
      • Retinal Consultants of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Part 1: Observation Control Arm; Observation Control
Experimental: Part 1: ABBV-RGX-314 Treatment Arm (Dose 1); ABBV-RGX-314 Dose 1	Genetic: ABBV-RGX-314 Dose 1; AAV8 vector containing a transgene for anti-VEGF fab (Dose 1); Other Names: Genetic/ Combination Product
Experimental: Part 1: ABBV-RGX-314 Treatment Arm (Dose 2); ABBV-RGX-314 Dose 2	Genetic: ABBV-RGX-314 Dose 2; AAV8 vector containing a transgene for anti-VEGF fab (Dose 2); Other Names: Genetic/ Combination Product
Experimental: Part 1: ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid; ABBV-RGX-314 Dose 3 and Topical Steroid	Drug: Topical Steroid; Topical Steroid; Genetic: ABBV-RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Names: Genetic/ Combination Product
Experimental: Part 2: ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid; ABBV-RGX-314 Dose 4 and Topical Steroid	Drug: Topical Steroid; Topical Steroid; Genetic: ABBV-RGX-314 Dose 4; AAV8 vector containing a transgene for anti-VEGF fab (Dose 4); Other Names: Genetic/ Combination Product
Active Comparator: Part 2: Aflibercept Control; Control treatment arm	Biological: Aflibercept; Aflibercept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.	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.	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.	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.	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.	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.	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.	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.	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.	At Week 24, Week 36, and Week 48
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	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.	At Week 54, Week 62, and Week 74 (Crossover (CO) participants)
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.	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.	At Week 54, Week 62, and Week 74 (Crossover participants)
Part 1: Mean change from baseline in the study eye in ETDRS-DRSS severity steps at Week 12, Week 24, Week 36, and Week 48 and (CO participants) change from Week 48 at Week 54, Week 62, and Week 74	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.	Baseline to Week 12, Week 24, Week 36, and Week 48; Week 48 to Week 54, Week 62, and Week 74 (Crossover participants)
Part 1: Incidences of overall and ocular AEs	To assess the safety and tolerability of ABBV-RGX-314	Through Week 48; and through Week 74 (Crossover participants)
Part 1: Vector shedding analysis in serum, urine, and tears	To assess the safety and tolerability of ABBV-RGX-314	Through Week 48; and through Week 74 (Crossover participants)
Part 1: Proportion of participants who experience ocular inflammation in the study eye following Suprachoroidal Space (SCS) ABBV-RGX-314 administration.	To evaluate the incidences of ocular inflammation following SCS ABBV-RGX-314 administration.	Through Week 48; and through Week 74 (Crossover participants)
Part 1: Proportion of participants requiring any additional intervention in the study eye for ocular diabetic complications	To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications	Through Week 48 or Week 74 (Crossover participants)
Part 1: Proportion of participants with any sight threatening ocular diabetic complications in the study eye based on duration of time to development of sight threatening ocular conditions	To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications	Day 1 to Week 48; Week 50 to Week 74 (Crossover participants)
Part 1:Proportion of participants developing ocular diabetic complications in the study eye requiring treatment per SOC based on number of treatments received and duration of time from intervention to first treatment per SOC	To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications	Day 1 to Week 48; Week 50 to Week 74 (Crossover participants)
Part 1: Proportion of participants developing ocular diabetic complications in the study eye requiring treatment per SOC based on duration of time from study intervention to first treatment and proportion of participants requiring more than 1 treatment	To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications	Day 1 to Week 48; or Week 50 to Week 74 (Crossover participants)
Part 1: Proportion of participants developing ocular diabetic complications in the study eye requiring surgical intervention per SOC based on duration of time from study intervention to surgical intervention	To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications	Day 1 to Week 48; or Week 50 to Week 74 (Crossover participants)
Part 1: Aqueous ABBV-RGX-314 TP concentration at assessed time points	To measure aqueous ABBV-RGX-314 TP concentrations	Through Week 48 or Week 74 (Crossover participants)
Part 1: Serum ABBV-RGX-314 TP concentration at assessed time points	To measure serum ABBV-RGX-314 TP concentrations	Through Week 48 or Week 74 (Crossover participants)
Part 2: Mean change from baseline in BCVA in the study eye over time	To evaluate the effect of ABBV-RGX-314 on BCVA over time	Through Week 54
Part 2: Proportion of participants with improved BCVA in the study eye over time	To evaluate the effect of ABBV-RGX-314 on BCVA over time	Through Week 54
Part 2: Proportion of participants with a worsening in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time	At Week 14, Week 30, Week 38, and Week 54
Part 2: Proportion of participants achieving an improvement in DR in the study eye per the ETDRS-DRSS on 4 widefield digital stereoscopic fundus photography	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time	At Week 14, Week 30, Week 38, and Week 54
Part 2: 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	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time	At Week 66 and Week 82 (Crossover participants)
Part 2: Proportion of participants with a worsening in DR in the study eye per the ETDRS-DRSS on 4-widefield digital stereoscopic fundus photography	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time	At Week 66 and Week 82 (Crossover participants)
Part 2: Mean change from baseline in the study eye in ETDRS-DRSS severity steps at Week 22, Week 38, and Week 54 and (CO participants) change from Week 56 at Week 74 and Week 82	To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time	Baseline to Week 22, Week 38, and Week 54; Week 56 to Week 74 and Week 82 (Crossover participants)
Part 2: Proportion of participants with an absence of CI-DME in the study eye	To evaluate the effect of ABBV-RGX-314 on CST (as determined by SD-OCT measurement) at Week 54.	At Week 54
Part 2: Incidences of overall and ocular AEs	To assess the safety and tolerability of ABBV-RGX-314	Through Week 54 or Week 82 (Crossover participants)
Part 2: Vector shedding analysis in serum, urine, and tears	To assess the safety and tolerability of ABBV-RGX-314	Through Week 54 or Week 82 (Crossover participants)
Part 2: Proportion of participants who experience ocular inflammation in the study eye following SCS ABBV-RGX-314 administration	To evaluate the incidences of ocular inflammation following SCS ABBV-RGX-314 administration	Through Week 54 or Week 82 (Crossover participants)
Part 2: Proportion of participants requiring any additional intervention in the study eye for ocular diabetic complications to Week 54 and (CO participants) Week 82	To evaluate the need for additional SOC intervention due to ocular diabetic complications	Through Week 54 or Week 82 (Crossover participants)
Part 2: Proportion of participants with any sight threatening ocular diabetic complications in the study eye based on duration of time to development of sight-threatening ocular conditions	To evaluate the need for additional SOC intervention due to ocular diabetic complications	Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)
Part 2: Proportion of participants developing ocular diabetic complications in the study eye requiring treatment per SOC based on number of treatments received and duration of time from study intervention to first treatment per SOC	To evaluate the need for additional SOC intervention due to ocular diabetic complications	Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)
Part 2: Proportion of participants developing ocular diabetic complications in the study eye requiring treatment per SOC based on duration of time from study intervention to first treatment and proportion of participants requiring more than 1 treatment	To evaluate the need for additional SOC intervention due to ocular diabetic complications	Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)
Part 2: Proportion of participants developing ocular diabetic complications in the study eye requiring surgical intervention per SOC	To evaluate the need for additional SOC intervention due to ocular diabetic complications	Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)
Part 2: Mean change from baseline in CST in the study eye on SD OCT at Week 30 and Week 54	To evaluate the effect of ABBV-RGX-314 on anatomic outcomes assessed using SD-OCT in all ABBV-RGX-314 treated participants	At Week 30 and Week 54
Part 2: Mean change from Week 54 in CST in the study eye on SD OCT at Week 82 (Crossover participants)	To evaluate the effect of ABBV-RGX-314 on anatomic outcomes assessed using SD-OCT in all ABBV-RGX-314 treated participants	At Week 82
Part 2: Proportion of participants achieving a reduction in CST in the study eye on SD-OCT at Week 30 and Week 54	To evaluate the effect of ABBV-RGX-314 on anatomic outcomes assessed using SD-OCT in all ABBV-RGX-314 treated participants	At Week 30 and Week 54
Part 2: Aqueous ABBV-RGX-314 TP concentration at assessed time points	To measure aqueous ABBV-RGX-314 TP concentrations	Through Week 54 or Week 82 (Crossover participants)
Part 2: Serum ABBV-RGX-314 TP concentration at assessed time points	To measure serum ABBV-RGX-314 TP concentrations	Through Week 54 or Week 82 (Crossover participants)

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: REGENXBIO Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: DR; CI-DME
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Eye Diseases; Diabetic Angiopathies; Diabetes Complications; Retinal Diseases; Diabetic Retinopathy; Polycyclic Compounds; Fused-Ring Compounds; aflibercept; Steroids
• Other Study ID Numbers: RGX-314-2202 (M23-414)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes