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

• ClinicalTrials.gov Identifier: NCT03999801
• Recruitment Status: Enrolling by invitation
• First Posted: June 27, 2019
• Last Update Posted: May 22, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Neovascular Age-related Macular Degeneration; Wet Macular Degeneration	Genetic: RGX-314	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 865 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: 1 main Observational study arm, 1 RGX-314 Fellow Eye Treatment substudy
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 31, 2019
• Estimated Primary Completion Date: December 2028
• Estimated Study Completion Date: December 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of ocular adverse events and any serious adverse events in the study eye [ Time Frame: 5 years inclusive of parent study ]
2. Fellow eye substudy: Incidence of ocular adverse events and any serious adverse events in the fellow eye [ Time Frame: 54 weeks ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Retinal Research Institute, LCC

Phoenix, Arizona, United States, 85053

United States, California

California Retina Consultants CRC

Santa Barbara, California, United States, 93103

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States, 02114

United States, Nevada

Sierra Eye Associates

Reno, Nevada, United States, 89502

United States, Pennsylvania

University of Pennsylvania Department of Ophthalmology

Philadelphia, Pennsylvania, United States, 19104

MidAtlantic Retina

Philadelphia, Pennsylvania, United States, 19107

United States, Tennessee

Charles Retina Institute

Germantown, Tennessee, United States, 38138

United States, Texas

Retina Consultants of Texas Research Center

The Woodlands, Texas, United States, 77384

Sponsors and Collaborators

AbbVie

More Information

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT03999801
• Other Study ID Numbers: RGX-314-5101
• First Posted: June 27, 2019
• Last Update Posted: May 22, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AbbVie:

gene therapy; wet AMD; nAMD

Additional relevant MeSH terms:

Macular Degeneration; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases