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Active, Not Recruiting

NCT Number: NCT04567550

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)

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Diabetic Retinopathy (DR) Cardiovascular Diseases Center-Involved Diabetic Macular Edema (CI-DME) Diabetes Complications Diabetes Mellitus Diabetic Angiopathies Diabetic Retinopathy Endocrine System Diseases Eye Diseases Retinal Diseases Vascular Diseases

Age range

25 year–89 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Barnet Dulaney Perkins Eye Center, Phoenix, Arizona, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ABBV-RGX-314 Dose 1

Genetic

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

Other names: Genetic/ Combination Product

ABBV-RGX-314 Dose 2

Genetic

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

Other names: Genetic/ Combination Product

ABBV-RGX-314 Dose 3

Genetic

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

Other names: Genetic/ Combination Product

Topical Steroid

Drug

Topical Steroid

ABBV-RGX-314 Dose 4

Genetic

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

Other names: Genetic/ Combination Product

Aflibercept

Biological

Aflibercept

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

    Time frame: At Week 48

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

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

    Time frame: At Week 54

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

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.

  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.

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.

  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.

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.

  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.

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.

  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.

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.

  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

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.

  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.

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.

  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

    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)

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.

  9. Part 1: Incidences of overall and ocular AEs

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

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

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

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

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

  11. Part 1: Proportion of participants who experience ocular inflammation in the study eye following Suprachoroidal Space (SCS) ABBV-RGX-314 administration.

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

    To evaluate the incidences of ocular inflammation following SCS ABBV-RGX-314 administration.

  12. Part 1: Proportion of participants requiring any additional intervention in the study eye for ocular diabetic complications

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

    To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications

  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

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

    To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications

  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

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

    To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications

  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

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

    To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications

  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

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

    To evaluate the need for additional Standard of Care (SOC) intervention due to ocular diabetic complications

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

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

    To measure aqueous ABBV-RGX-314 TP concentrations

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

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

    To measure serum ABBV-RGX-314 TP concentrations

  19. Part 2: Mean change from baseline in BCVA in the study eye over time

    Time frame: Through Week 54

    To evaluate the effect of ABBV-RGX-314 on BCVA over time

  20. Part 2: Proportion of participants with improved BCVA in the study eye over time

    Time frame: Through Week 54

    To evaluate the effect of ABBV-RGX-314 on BCVA over time

  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

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time

  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

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time

  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

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time

  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

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time

  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

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

    To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time

  26. Part 2: Proportion of participants with an absence of CI-DME in the study eye

    Time frame: At Week 54

    To evaluate the effect of ABBV-RGX-314 on CST (as determined by SD-OCT measurement) at Week 54.

  27. Part 2: Incidences of overall and ocular AEs

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

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

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

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

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

  29. Part 2: Proportion of participants who experience ocular inflammation in the study eye following SCS ABBV-RGX-314 administration

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

    To evaluate the incidences of ocular inflammation following SCS ABBV-RGX-314 administration

  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

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

    To evaluate the need for additional SOC intervention due to ocular diabetic complications

  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

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

    To evaluate the need for additional SOC intervention due to ocular diabetic complications

  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

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

    To evaluate the need for additional SOC intervention due to ocular diabetic complications

  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

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

    To evaluate the need for additional SOC intervention due to ocular diabetic complications

  34. Part 2: Proportion of participants developing ocular diabetic complications in the study eye requiring surgical intervention per SOC

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

    To evaluate the need for additional SOC intervention due to ocular diabetic complications

  35. Part 2: Mean change from baseline in CST in the study eye on SD OCT at Week 30 and Week 54

    Time frame: 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

  36. Part 2: Mean change from Week 54 in CST in the study eye on SD OCT at Week 82 (Crossover participants)

    Time frame: At Week 82

    To evaluate the effect of ABBV-RGX-314 on anatomic outcomes assessed using SD-OCT in all ABBV-RGX-314 treated participants

  37. Part 2: Proportion of participants achieving a reduction in CST in the study eye on SD-OCT at Week 30 and Week 54

    Time frame: 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

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

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

    To measure aqueous ABBV-RGX-314 TP concentrations

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

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

    To measure serum ABBV-RGX-314 TP concentrations

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • REGENXBIO Inc.

Registry information

Official study title

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)

Acronym: ALTITUDE®

Important dates

Study start
2020
Primary completion
2026
Study completion
2026
First posted
Sep 28, 2020
Registry last updated
Sep 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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