Long-term Follow-Up Study of RGX-314 and Fellow Eye Substudy (RGX-314 SRLTFU)

A Long-term Follow-Up Study to Evaluate the Safety and Efficacy of RGX-314 Following Subretinal Administration in Participants With Neovascular Age-related Macular Degeneration and Fellow Eye Treatment Substudy

This is a prospective, observational study designed to evaluate the long-term safety and efficacy of RGX-314. Eligible participants are those who were previously enrolled in a clinical study in which they received a single subretinal administration of RGX-314 in their study eye. Enrollment of each participant in the current study should occur after the participant has completed either the end of study or early termination visit in the previous (parent) clinical study. Participants will be followed for up to 5 years post-RGX-314 administration (inclusive of the parent study). After enrollment and a 6-month follow-up visit, participants will attend at least annual study visits through the end of the 5-year post-RGX-314 administration follow-up period.

Additionally, an interventional fellow eye treatment substudy will evaluate the safety, efficacy, and immunogenicity of subretinal RGX-314 administration in the fellow eye of participants having bilateral disease who previously received a subretinal injection of RGX-314 in their study eye. Participants who qualify for the substudy will receive subretinal administration of RGX-314 in their fellow eye and complete 13 study visits in a 54-week period. Following completion of the substudy participants will continue in the observational portion of the study for up to 5 years post RGX-314 administration in their fellow eye.

Study Overview

• Status: Enrolling by invitation
• Conditions: Wet Macular Degeneration; Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Genetic: RGX-314

• Study Type: Interventional
• Enrollment (Estimated): 865
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute, LCC
  • California
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants CRC
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • MidAtlantic Retina
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Department of Ophthalmology
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
  • Texas
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Texas Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

All subjects that previously received RGX-314 in a parent study are enrolled into this arm.

Description

Main Observational Study:

Inclusion Criteria:

1. Able and willing to provide written consent
2. Previously enrolled in a clinical study of RGX-314 and received a single subretinal administration of RGX-314

Exclusions Criteria:

1. None

Fellow Eye Substudy:

Inclusion Criteria

1. Age ≤ 93 years
2. Currently or previously enrolled in the main observational study
3. Diagnosis of bilateral choroidal neovascularization secondary to age-related macular degeneration
4. Active nAMD in the fellow eye
5. BCVA between ≤ 80 and ≥ 20 letters in the fellow eye

Exclusion Criteria:

1. CNV or macular edema in the fellow eye secondary to causes other than nAMD
2. Subfoveal fibrosis or atrophy in the fellow eye
3. Advanced glaucoma or history of secondary glaucoma in the fellow eye or any invasive procedure to treat glaucoma
4. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
5. History of intraocular surgery in the fellow eye within 12 weeks of screening
6. History of intravitreal therapy, such as intravitreal steroid injection or investigational product, other than an intravitreal therapy for nAMD, in the fellow eye within 6 months of screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Main Observational Study; All subjects that previously received RGX-314 in a subretinal administration parent study are enrolled into this arm.
Experimental: RGX-314 Fellow Eye Treatment Substudy; RGX-314 Fellow Eye Treatment	Genetic: RGX-314; AAV8 vector containing a transgene for anti-VEGF Fab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of ocular adverse events and any serious adverse events in the study eye	5 years inclusive of parent study
Fellow eye substudy: Incidence of ocular adverse events and any serious adverse events in the fellow eye	54 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in best corrected visual acuity (BCVA) in the study eye	Mean change and proportion of participants losing greater than or equal to 5, 10, and 15 letters	5 years inclusive of parent study
Change from baseline in Central Retinal Thickness (CRT) in the study eye	Mean change from baseline in CRT as measured by spectral domain optical coherence tomography (SD-OCT)	5 years inclusive of parent study
Number of supplemental anti-VEGF injections in the study eye	Mean number of supplemental anti-VEGF injections based on chart review	5 years inclusive of parent study
Number of retinal specialist visits for the study eye	Mean number of retinal specialist visits attended for nAMD based on chart review	5 years inclusive of parent study
Fellow eye substudy: Change from baseline in best corrected visual acuity	Mean change from baseline in BCVA in the fellow eye	54 weeks
Fellow eye substudy: Change from baseline in Central Retinal Thickness in the fellow eye	Mean change from baseline in CRT in the fellow eye as measured by SD-OCT	54 weeks
Fellow eye substudy: Number of supplemental anti-VEGF injections in the fellow eye	Mean number of supplemental anti-VEGF injections in the fellow eye	54 weeks
Fellow eye substudy: Aqueous and Serum RGX-314 transgene product (TP) concentrations in the fellow eye	Fellow eye aqueous and serum RGX-314 TP concentrations at assessed time points	54 weeks
Fellow eye substudy: Immunogenicity measurements in the fellow eye	Fellow eye immunogenicity measurements at assessed timepoints	54 weeks

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2019
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: June 24, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): June 17, 2024
• Last Update Submitted That Met QC Criteria: June 14, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: gene therapy; wet AMD; nAMD
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: RGX-314-5101

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: No