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Active, not recruitingNCT04567550ALTITUDE®Updated Aug 19, 2026

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)

A Phase 2 interventional study of ABBV-RGX-314 Dose 1 and ABBV-RGX-314 Dose 2 in Diabetic Retinopathy (DR) and Center-Involved Diabetic Macular Edema (CI-DME), sponsored by AbbVie. Active, not recruiting at 25 sites in United States. Open to participants aged 25 Years to 89 Years. Per ClinicalTrials.gov, last updated 2026-08-19.

Sponsored by AbbVie · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
139
Allocation
Randomized
Ages
25 Years to 89 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

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

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Keywords

  • DR
  • CI-DME
03

In context

Diabetic Retinopathy

773 studies on the registry are indexed under Diabetic Retinopathy; 139 are open to participants now.

This study's enrollment of 139 is above the median of 78 across 480 interventional studies indexed under Diabetic Retinopathy.

Browse Diabetic Retinopathy studies →

Lead sponsor

AbbVie is the lead sponsor of 953 studies on the registry; 136 are open to participants now.

Of its 350 completed or terminated interventional studies of FDA-regulated products, 210 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
25 Years to 89 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
139 participants (actual)

Study arms

  • 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

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

    ABBV-RGX-314 Dose 2

    Genetic: ABBV-RGX-314 Dose 2

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

    ABBV-RGX-314 Dose 3 and Topical Steroid

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

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

    ABBV-RGX-314 Dose 4 and Topical Steroid

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

  • Active comparator
    Part 2: Aflibercept Control

    Control treatment arm

    Biological: Aflibercept

Interventions

  • GeneticABBV-RGX-314 Dose 1

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

    Also known as: Genetic/ Combination Product

  • GeneticABBV-RGX-314 Dose 2

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

    Also known as: Genetic/ Combination Product

  • GeneticABBV-RGX-314 Dose 3

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

    Also known as: Genetic/ Combination Product

  • DrugTopical Steroid

    Topical Steroid

  • GeneticABBV-RGX-314 Dose 4

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

    Also known as: Genetic/ Combination Product

  • BiologicalAflibercept

    Aflibercept

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

  1. 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.

    Time frame: At Week 4, Week 12, Week 24, and Week 36

  2. 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.

    Time frame: At Week 4, Week 12, Week 24, Week 36, and Week 48

  3. 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.

    Time frame: At Week 4, Week 12, Week 24, Week 36, and Week 48

  4. 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.

    Time frame: At Week 4, Week 12, Week 24, Week 36, and Week 48

  5. 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.

    Time frame: At Week 24, Week 36, and Week 48

  6. 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.

    Time frame: At Week 54, Week 62, and Week 74 (Crossover (CO) participants)

  7. 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.

    Time frame: At Week 54, Week 62, and Week 74 (Crossover participants)

  8. 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.

    Time frame: Baseline to Week 12, Week 24, Week 36, and Week 48; Week 48 to Week 54, Week 62, and Week 74 (Crossover participants)

  9. Part 1: Incidences of overall and ocular AEs

    To assess the safety and tolerability of ABBV-RGX-314

    Time frame: Through Week 48; and through Week 74 (Crossover participants)

  10. Part 1: Vector shedding analysis in serum, urine, and tears

    To assess the safety and tolerability of ABBV-RGX-314

    Time frame: Through Week 48; and through Week 74 (Crossover participants)

  11. 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.

    Time frame: Through Week 48; and through Week 74 (Crossover participants)

  12. 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

    Time frame: Through Week 48 or Week 74 (Crossover participants)

  13. 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

    Time frame: Day 1 to Week 48; Week 50 to Week 74 (Crossover participants)

  14. 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

    Time frame: Day 1 to Week 48; Week 50 to Week 74 (Crossover participants)

  15. 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

    Time frame: Day 1 to Week 48; or Week 50 to Week 74 (Crossover participants)

  16. 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

    Time frame: Day 1 to Week 48; or Week 50 to Week 74 (Crossover participants)

  17. Part 1: Aqueous ABBV-RGX-314 TP concentration at assessed time points

    To measure aqueous ABBV-RGX-314 TP concentrations

    Time frame: Through Week 48 or Week 74 (Crossover participants)

  18. Part 1: Serum ABBV-RGX-314 TP concentration at assessed time points

    To measure serum ABBV-RGX-314 TP concentrations

    Time frame: Through Week 48 or Week 74 (Crossover participants)

  19. 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

    Time frame: Through Week 54

  20. 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

    Time frame: Through Week 54

  21. 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

    Time frame: At Week 14, Week 30, Week 38, and Week 54

  22. 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

    Time frame: At Week 14, Week 30, Week 38, and Week 54

  23. 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

    Time frame: At Week 66 and Week 82 (Crossover participants)

  24. 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

    Time frame: At Week 66 and Week 82 (Crossover participants)

  25. 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

    Time frame: Baseline to Week 22, Week 38, and Week 54; Week 56 to Week 74 and Week 82 (Crossover participants)

  26. 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.

    Time frame: At Week 54

  27. Part 2: Incidences of overall and ocular AEs

    To assess the safety and tolerability of ABBV-RGX-314

    Time frame: Through Week 54 or Week 82 (Crossover participants)

  28. Part 2: Vector shedding analysis in serum, urine, and tears

    To assess the safety and tolerability of ABBV-RGX-314

    Time frame: Through Week 54 or Week 82 (Crossover participants)

  29. 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

    Time frame: Through Week 54 or Week 82 (Crossover participants)

  30. 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

    Time frame: Through Week 54 or Week 82 (Crossover participants)

  31. 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

    Time frame: Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)

  32. 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

    Time frame: Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)

  33. 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

    Time frame: Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)

  34. 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

    Time frame: Day 1 to Week 54; Week 56 to Week 82 (Crossover participants)

  35. 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

    Time frame: At Week 30 and Week 54

  36. 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

    Time frame: At Week 82

  37. 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

    Time frame: At Week 30 and Week 54

  38. Part 2: Aqueous ABBV-RGX-314 TP concentration at assessed time points

    To measure aqueous ABBV-RGX-314 TP concentrations

    Time frame: Through Week 54 or Week 82 (Crossover participants)

  39. Part 2: Serum ABBV-RGX-314 TP concentration at assessed time points

    To measure serum ABBV-RGX-314 TP concentrations

    Time frame: Through Week 54 or Week 82 (Crossover participants)

07

Study locations

25 sites
  • Retinal Research Institute, LLC
    Phoenix, Arizona 85014, United States
  • Barnet Dulaney Perkins Eye Center
    Phoenix, Arizona 85016, United States
  • California Retina Consultants
    Bakersfield, California 93309, United States
  • Retina-Vitreous Associates Medical Group
    Beverly Hills, California 90017, United States
  • Retinal Diagnostic Center
    Campbell, California 95008, United States
  • Northern California Retina Vitreous Associates Medical Group, Inc.
    Mountain View, California 94040, United States
  • California Eye Specialists Medical Group, Inc
    Pasadena, California 91107, United States
  • Retinal Consultants San Diego
    Poway, California 92064, United States
  • California Retina Consultants
    Santa Barbara, California 93103, United States
  • Southeast Retina Center, PC
    Augusta, Georgia 30909, United States
  • University Retina and Macula Associates, PC
    Oak Forest, Illinois 60452, United States
  • Springfield Clinic
    Springfield, Illinois 62702, United States
  • Wilmer Eye Institute/Johns Hopkins University School of Medicine
    Baltimore, Maryland 21287, United States
  • Cumberland Valley Retina Consultants
    Hagerstown, Maryland 21740, United States
  • Ophthalmic Consultants of Boston
    Boston, Massachusetts 02114, United States
  • Sierra Eye Associates
    Reno, Nevada 89502, United States
  • NJ Retina
    Teaneck, New Jersey 07666, United States
  • Vision Research Center Eye Associates of New Mexico
    Albuquerque, New Mexico 87109, United States
  • Duke University Eye Center
    Durham, North Carolina 27705, United States
  • Mid Atlantic Retina
    Philadelphia, Pennsylvania 19107, United States
  • Charles Retina Institute, P.C.
    Germantown, Tennessee 38138, United States
  • Retina Research Institute of Texas, LLC
    Abilene, Texas 79606, United States
  • Austin Clinical Research, LLC
    Austin, Texas 78750, United States
  • Star Retina
    Burleson, Texas 76028, United States
  • Retinal Consultants of Texas
    The Woodlands, Texas 77384, United States
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 19, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04567550
Lead sponsor
AbbVie
Collaborators
REGENXBIO Inc.
Responsible party
Sponsor
First posted
Sep 28, 2020
Start date
Nov 20, 2020
Primary completion
Jun 18, 2026
Completion
Dec 2026 (estimated)
Last update
Aug 19, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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