Diabetic Retinopathy (DR)Phase 2ALTITUDE®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)
A Phase 2 study testing ABBV-RGX-314 Dose 1, ABBV-RGX-314 Dose 2 and ABBV-RGX-314 Dose 3 in people with Diabetic Retinopathy (DR) and Center-Involved Diabetic Macular Edema (CI-DME), run by AbbVie at 25 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 89 years
- Conditions the study is for
- Diabetic Retinopathy (DR), Center-Involved Diabetic Macular Edema (CI-DME)
- What is being tested?
- ABBV-RGX-314 Dose 1, ABBV-RGX-314 Dose 2 and ABBV-RGX-314 Dose 3
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 25 sitesUnited States
- Study dates
- 20 Nov 2020to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Patients 25-89 years of age with diabetic retinopathy secondary to diabetes mellitus Type 1 or 2.
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- 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
Who cannot join
- 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.
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- Part 2 (DR with CI-DME):
- 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.
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Retina Research Institute of Texas, LLC
Abilene, Texas, 79606
Vision Research Center Eye Associates of New Mexico
Albuquerque, New Mexico, 87109
Southeast Retina Center, PC
Augusta, Georgia, 30909
Austin Clinical Research, LLC
Austin, Texas, 78750
California Retina Consultants
Bakersfield, California, 93309
Wilmer Eye Institute/Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287
Retina-Vitreous Associates Medical Group
Beverly Hills, California, 90017
Ophthalmic Consultants of Boston
Boston, Massachusetts, 02114
Star Retina
Burleson, Texas, 76028
Retinal Diagnostic Center
Campbell, California, 95008
Duke University Eye Center
Durham, North Carolina, 27705
Charles Retina Institute, P.C.
Germantown, Tennessee, 38138
Cumberland Valley Retina Consultants
Hagerstown, Maryland, 21740
Northern California Retina Vitreous Associates Medical Group, Inc.
Mountain View, California, 94040
University Retina and Macula Associates, PC
Oak Forest, Illinois, 60452
California Eye Specialists Medical Group, Inc
Pasadena, California, 91107
Mid Atlantic Retina
Philadelphia, Pennsylvania, 19107
Retinal Research Institute, LLC
Phoenix, Arizona, 85014
Barnet Dulaney Perkins Eye Center
Phoenix, Arizona, 85016
Retinal Consultants San Diego
Poway, California, 92064
Sierra Eye Associates
Reno, Nevada, 89502
California Retina Consultants
Santa Barbara, California, 93103
Springfield Clinic
Springfield, Illinois, 62702
NJ Retina
Teaneck, New Jersey, 07666
Retinal Consultants of Texas
The Woodlands, Texas, 77384
About this study
Official 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)
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.
- Being tested
- ABBV-RGX-314 Dose 1, ABBV-RGX-314 Dose 2, ABBV-RGX-314 Dose 3, Topical Steroid, ABBV-RGX-314 Dose 4
- Keywords
- DR, CI-DME
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABBV-RGX-314 Dose 1Genetic
Also called Genetic/ Combination Product
AAV8 vector containing a transgene for anti-VEGF fab (Dose 1)
ABBV-RGX-314 Dose 2Genetic
Also called Genetic/ Combination Product
AAV8 vector containing a transgene for anti-VEGF fab (Dose 2)
ABBV-RGX-314 Dose 3Genetic
Also called Genetic/ Combination Product
AAV8 vector containing a transgene for anti-VEGF fab (Dose 3)
Topical SteroidDrug
Topical Steroid
ABBV-RGX-314 Dose 4Genetic
Also called Genetic/ Combination Product
AAV8 vector containing a transgene for anti-VEGF fab (Dose 4)
AfliberceptBiological
Aflibercept
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Observation Control Arm | No intervention | Observation Control |
| Part 1: ABBV-RGX-314 Treatment Arm (Dose 1) | Experimental | ABBV-RGX-314 Dose 1 Receives: Genetic: ABBV-RGX-314 Dose 1 |
| Part 1: ABBV-RGX-314 Treatment Arm (Dose 2) | Experimental | ABBV-RGX-314 Dose 2 Receives: 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 Receives: 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 Receives: Drug: Topical Steroid; Genetic: ABBV-RGX-314 Dose 4 |
| Part 2: Aflibercept Control | Active comparator | Control treatment arm Receives: Biological: Aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
To evaluate the effect of ABBV-RGX-314 on DR (ETDRS-DRSS) over time.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: At Week 54
Part 2: Incidences of overall and ocular AEs
To assess the safety and tolerability of ABBV-RGX-314
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Through Week 54 or Week 82 (Crossover participants)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2020
- Study start20 Nov 2020
- Primary completion18 Jun 2026
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Retinopathy (DR)Studies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- REGENXBIO Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04567550
- Sponsor's protocol ID
- RGX-314-2202 (M23-414)
- Acronym
- ALTITUDE®
- Status last verified
- Aug 2026
- First submitted
- 15 Sep 2020
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT04567550
- Acronym / sponsor ID
- ALTITUDE® / RGX-314-2202 (M23-414)
- Keywords
- DR, CI-DME
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 139 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Collaborators
- REGENXBIO Inc.
- Study start
- 20 Nov 2020 (actual)
- Primary completion
- 18 Jun 2026 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 28 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1: Observation Control Arm | No intervention | –Observation Control |
| Part 1: ABBV-RGX-314 Treatment Arm (Dose 1) | Experimental | Genetic: ABBV-RGX-314 Dose 1ABBV-RGX-314 Dose 1 |
| Part 1: ABBV-RGX-314 Treatment Arm (Dose 2) | Experimental | Genetic: ABBV-RGX-314 Dose 2ABBV-RGX-314 Dose 2 |
| Part 1: ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid | Experimental | Genetic: ABBV-RGX-314 Dose 3, Drug: Topical SteroidABBV-RGX-314 Dose 3 and Topical Steroid |
| Part 2: ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid | Experimental | Drug: Topical Steroid, Genetic: ABBV-RGX-314 Dose 4ABBV-RGX-314 Dose 4 and Topical Steroid |
| Part 2: Aflibercept Control | Active comparator | Biological: AfliberceptControl treatment arm |
Who may qualify
- Ages
- 25 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABBV-RGX-314 Dose 1Also: Genetic/ Combination ProductAAV8 vector containing a transgene for anti-VEGF fab (Dose 1) | Genetic | Part 1: ABBV-RGX-314 Treatment Arm (Dose 1) |
| ABBV-RGX-314 Dose 2Also: Genetic/ Combination ProductAAV8 vector containing a transgene for anti-VEGF fab (Dose 2) | Genetic | Part 1: ABBV-RGX-314 Treatment Arm (Dose 2) |
| ABBV-RGX-314 Dose 3Also: Genetic/ Combination ProductAAV8 vector containing a transgene for anti-VEGF fab (Dose 3) | Genetic | Part 1: ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid |
| Topical SteroidTopical Steroid | Drug | 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 4Also: Genetic/ Combination ProductAAV8 vector containing a transgene for anti-VEGF fab (Dose 4) | Genetic | Part 2: ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid |
| AfliberceptAflibercept | Biological | Part 2: Aflibercept Control |
Primary outcome
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.
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.
39 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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
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)
Part 1: Incidences of overall and ocular AEs
Time frame: Through Week 48; and through Week 74 (Crossover participants)
Part 1: Vector shedding analysis in serum, urine, and tears
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Through Week 48 or Week 74 (Crossover participants)
Part 1: Serum ABBV-RGX-314 TP concentration at assessed time points
Time frame: Through Week 48 or Week 74 (Crossover participants)
Part 2: Mean change from baseline in BCVA in the study eye over time
Time frame: Through Week 54
Part 2: Proportion of participants with improved BCVA in the study eye over time
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At Week 54
Part 2: Incidences of overall and ocular AEs
Time frame: Through Week 54 or Week 82 (Crossover participants)
Part 2: Vector shedding analysis in serum, urine, and tears
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: At Week 30 and Week 54
Part 2: Aqueous ABBV-RGX-314 TP concentration at assessed time points
Time frame: Through Week 54 or Week 82 (Crossover participants)
Part 2: Serum ABBV-RGX-314 TP concentration at assessed time points
Time frame: Through Week 54 or Week 82 (Crossover participants)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ABBV-RGX-314 Dose 1, ABBV-RGX-314 Dose 2 and ABBV-RGX-314 Dose 3 in people with Diabetic Retinopathy (DR) and Center-Involved Diabetic Macular Edema (CI-DME), run by AbbVie at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.