RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Neovascular Age-Related Macular Degeneration (nAMD) (AAVIATE)

A Phase 2, Randomized, Dose-escalation, Ranibizumab-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of RGX-314 Gene Therapy Delivered Via One or Two Suprachoroidal Space (SCS) Injections in Participants With Neovascular Age-Related Macular Degeneration (nAMD) (AAVIATE)

This interventional study is being conducted with an investigational gene therapy treatment called ABBV-RGX-314 (also known as RGX-314) and is being developed as a potential one-time gene therapy treatment for neovascular (wet) age-related macular degeneration (wet AMD or nAMD). The typical treatment for nAMD is frequent injections of anti-VEGF therapy. Researchers are testing ABBV-RGX-314 to see if it has similar effects as the current approved standard of care, such as Lucentis® or Eylea® injections.

The duration of this study will be up to 52 weeks or for ranibizumab control participants who cross over to ABBV-RGX-314 after week 52, up to 80 weeks post-randomization.

The primary outcome measure for this investigational study is to evaluate the mean change in best-corrected visual acuity (BCVA) for ABBV-RGX-314 compared with ranibizumab monthly at the Week 40 visit.

Study Overview

• Status: Active, not recruiting
• Conditions: Neovascular Age-Related Macular Degeneration (nAMD)
• Intervention / Treatment: Biological: Ranibizumab; Drug: Local Steroid; 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

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 nAMD.

ABBV-RGX-314 will be injected into the SCS part of the eye. Approximately 140 participants who meet the inclusion/exclusion criteria will be enrolled into one of 7 cohorts. Participants will be randomized in Cohorts 1 and 2 to receive ABBV-RGX-314 or the intravitreal ranibizumab control. Participants enrolled in Cohorts 3 through 5 will receive ABBV-RGX-314. Participants enrolled in Cohort 6 will receive ABBV-RGX-314 and will be randomized to one of two different post-procedural steroid regimens. Participants randomized in Cohort 7 will receive ABBV-RGX-314 with a protocol mandated steroid regimen or the intravitreal ranibizumab control. Cohort 1 will evaluate ABBV-RGX-314 Dose 1, Cohorts 2 and 3 will evaluate ABBV-RGX-314 Dose 2, Cohorts 4, 5, and 6 will evaluate ABBV-RGX-314 Dose 3, and Cohort 7 will evaluate ABBV-RGX-314 Dose 4.

The duration of the study will be up to 52 weeks or for ranibizumab control participants who cross over to ABBV-RGX-314, up to 80 weeks post-randomization.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute /ID# 255925
  • California
    • Bakersfield, California, United States, 93309-1677
      • California Retina Consultants - Bakersfield /ID# 255910
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Assoc Med Grp /ID# 255921
    • Campbell, California, United States, 95008
      • Retinal Diagnostic Center /ID# 272275
    • Mountain View, California, United States, 94040-4101
      • Northern California Retina Vitreous Associates Medical Group, Inc /ID# 255920
    • Poway, California, United States, 92064-2530
      • Retina Consultants of San Diego /ID# 255911
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants - Santa Barbara /ID# 255923
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center /ID# 255912
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic - First /ID# 272274
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital /ID# 255919
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston /ID# 255917
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates /ID# 255908
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Eye Associates of New Mexico /ID# 255915
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center /ID# 267646
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina /ID# 255906
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute /ID# 255922
    • Nashville, Tennessee, United States, 37203-1513
      • Tennessee Retina - Nashville /ID# 255918
  • Texas
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants - The Woodlands /ID# 255924

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >/= 50 and </= 89
• Diagnosis of CNV secondary to age-related macular degeneration in the study eye.
• Participants must have demonstrated a meaningful response to anti-VEGF therapy.
• Willing and able to provide written, signed informed consent for this study.

Exclusion Criteria:

• CNV or macular edema in the study eye secondary to any causes other than AMD.
• Subfoveal fibrosis or atrophy in study eye.
• Participants who have had a prior vitrectomy.
• Active or history of retinal detachment in the study eye.
• History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product (IP), other than anti-VEGF therapy, in the 6 months prior to study entry.
• Received any gene therapy.
• Any condition preventing visualization of the fundus or VA improvement in the study eye, eg, cataract.
• History of intraocular surgery in the study eye within 12 weeks of study entry.
• Receipt of any IP within 30 days of study entry or 5 half-lives of the IP.
• Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within 6 months of study entry.
• Cohorts 1 - 5 only: Uncontrolled glaucoma in the study eye.

COHORT 6 AND 7 ONLY:

• Active or history of glaucoma or ocular hypertension (steroid-induced ocular hypertension (Cohort 7 only)) in the study eye.
• Certain OCT characteristics including: Large Pigment Epithelial Detachments (PED), clinically significant Epiretinal Membrane (ERM) in the study eye at Visit 1.

Note: Other inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ranibizumab control; Control treatment arm	Biological: Ranibizumab; Ranibizumab (anti-VEGF agent)
Experimental: 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: Combination Product
Experimental: 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: Combination Product
Experimental: ABBV-RGX-314 Treatment Arm (Dose 3); ABBV-RGX-314 Dose 3	Genetic: ABBV-RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Names: Combination Product
Experimental: ABBV-RGX-314 Treatment Arm (Dose 3) and Local Steroid; ABBV-RGX-314 Dose 3 and Local Steroid	Drug: Local Steroid; Local steroid; Genetic: ABBV-RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Names: Combination Product
Experimental: 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: Combination Product
Experimental: 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: Combination Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in BCVA to Week 40 based on the Early Treatment Diabetic Retinopathy Study (ETDRS) score	The scale used is the early treatment diabetic retinopathy study (ETDRS) letter score from 0-100 and higher score being better vision.	40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of overall and ocular adverse events (AEs) and serious adverse events (SAEs)	Incidence of overall and ocular adverse events (AEs) and serious adverse events (SAEs)	52 weeks
Vector shedding analysis in serum, urine, and tears	Evaluate the safety and tolerability of ABBV-RGX-314	52 Weeks
Proportion of participants who experience ocular inflammation following SCS ABBV-RGX-314 administration	To evaluate the incidences of ocular inflammation following SCS ABBV-RGX-314 administration	52 weeks
Mean change from baseline in choroidal neovascularization (CNV) lesion size and leakage area based on fluorescein angiography (FA)	To evaluate the effect of ABBV-RGX-314 on CNV lesion growth and leakage as measured by FA	Up to Week 80
Mean change from baseline in BCVA based on ETDRS score	Evaluate the effect of ABBV-RGX-314 on BCVA	Up to Week 80
Proportion of participants (1) gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 letters; (2) losing ≥ 15, ≥ 10, ≥ 5, or > 0 letters (3) maintaining vision (not losing ≥ 15 letters) compared with baseline as per BCVA	To evaluate the effect of ABBV-RGX-314 on BCVA	Up to Week 52
Mean change from baseline in CRT as measured by SD-OCT	To evaluate the effect of ABBV-RGX-314 on CRT, as measured by SD-OCT	Up to Week 80
Mean supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 treatment arms	To assess the need for supplemental anti-VEGF therapy in participants who receive ABBV-RGX-314 treatment	Up to Week 80
Proportion of participants who have a reduction of ≥ 50% and ≥ 75% in supplemental anti-VEGF- injection annualized rate	Proportion of participants who have a reduction of ≥ 50% and ≥ 75% in supplemental anti-VEGF- injection annualized rate through Week 40 and Week 52 compared with the prior 52 weeks preceding the first intravitreal ranibizumab injection received as part of the Screening Period (ABBV-RGX-314 administered participants)	52 Weeks
Proportion of participants with 0, ≤ 1, and ≤ 2 supplemental injections	To assess the need for supplemental anti-VEGF therapy in participants who receive ABBV-RGX-314 treatment	Up to Week 80
Mean percent reduction in supplemental anti-VEGF injection annualized rate	To assess the need for supplemental anti-VEGF therapy in participants who receive ABBV-RGX-314 treatment	Up to Week 80
Time from ABBV-RGX-314 administration to first supplemental anti-VEGF injection	To assess the need for supplemental anti-VEGF therapy in participants who receive ABBV-RGX-314 treatment	80 Weeks
Aqueous humor ABBV-RGX- 314 TP concentration over time	To evaluate the concentration of ABBV-RGX-314 TP in aqueous humor and serum	52 Weeks
Mean change from baseline in serum ABBV-RGX-314 TP concentration over time	To evaluate the concentration of ABBV-RGX-314 TP in aqueous humor and serum	80 Weeks

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: REGENXBIO Inc.
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: AMD; wet AMD; wAMD; nAMD
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Retinal Diseases; Retinal Degeneration; Choroid Diseases; Eye Abnormalities; Choroidal Effusions; Macular Degeneration; Wet Macular Degeneration; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Polycyclic Compounds; Amides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Fused-Ring Compounds; Drug Combinations; Penicillin G; beta-Lactams; Lactams; Sulfones; Tazobactam; Penicillanic Acid; Piperacillin; Ampicillin; Penicillins; Ranibizumab; Piperacillin, Tazobactam Drug Combination; Steroids
• Other Study ID Numbers: RGX-314-2102 (M23-411); M23-411 (Other Identifier: AbbVie Inc)

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
• product manufactured in and exported from the U.S.: No