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)

RGX-314 is being developed as a potential novel one-time gene therapy treatment for the treatment of neovascular (wet) age related macular degeneration (wet AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to twelve weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time.

Study Overview

• Status: Recruiting
• Conditions: Neovascular Age-Related Macular Degeneration (nAMD)
• Intervention / Treatment: Biological: Ranibizumab; Genetic: RGX-314 Dose 1; Genetic: RGX-314 Dose 2; Genetic: RGX-314 Dose 3; Drug: Local steroid; Drug: Topical steroid

Detailed Description

This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of RGX-314 gene therapy in subjects with nAMD. Approximately 115 participants who meet the inclusion/exclusion criteria will be enrolled into one of 6 cohorts. Participants will be randomized in Cohorts 1 and 2 to receive RGX-314 or ranibizumab control, and participants enrolled in Cohorts 3 through 5 will receive RGX-314. Participants enrolled in Cohort 6 will receive RGX-314 and will be randomized to one of two different post-procedural steroid regimens. Cohort 1 will evaluate RGX-314 Dose 1, Cohorts 2 and 3 will evaluate RGX-314 Dose 2, and Cohorts 4, 5, and 6 will evaluate RGX-314 Dose 3. Participants will be evaluated for efficacy, safety and tolerability of RGX-314 throughout the study.

• Study Type: Interventional
• Enrollment (Anticipated): 115
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Patient Advocacy; Phone Number: 1-866-860-0117; Email: patientadvocacy@regenxbio.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Recruiting
      • Phoenix Location
      • Contact: Principal Investigator
  • California
    • Bakersfield, California, United States, 93309
      • Active, not recruiting
      • Bakersfield Location
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Beverly Hills Location
      • Contact: Principal Investigator
    • Mountain View, California, United States, 94040
      • Recruiting
      • Mountain View Location
      • Contact: Principal Investigator
    • Poway, California, United States, 92064
      • Recruiting
      • Poway Location
      • Contact: Principal Investigator
    • Santa Barbara, California, United States, 93103
      • Active, not recruiting
      • Santa Barbara Location
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Recruiting
      • Augusta Location
      • Contact: Principal Investigator
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Baltimore Location
      • Contact: Principal Investigator
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Boston Location
      • Contact: Principal Investigator
  • Nevada
    • Reno, Nevada, United States, 89502
      • Recruiting
      • Reno Location
      • Contact: Principal Investigator
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Recruiting
      • Albuquerque Location
      • Contact: Principal Investigator
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Philadelphia Location
      • Contact: Principal Investigator
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Active, not recruiting
      • Germantown Location
    • Nashville, Tennessee, United States, 37203
      • Active, not recruiting
      • Nashville location
  • Texas
    • The Woodlands, Texas, United States, 77384
      • Active, not recruiting
      • Woodlands Location

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 87 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 ONLY:

  • Active or history of glaucoma or ocular hypertension 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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ranibizumab control; Control treatment arm	Biological: Ranibizumab; Ranibizumab (anti-VEGF agent)
Experimental: RGX-314 Treatment Arm (Dose 1); RGX-314 Dose 1	Genetic: RGX-314 Dose 1; AAV8 vector containing a transgene for anti-VEGF fab (Dose 1); Other Names: Combination Product
Experimental: RGX-314 Treatment Arm (Dose 2); RGX-314 Dose 2	Genetic: RGX-314 Dose 2; AAV8 vector containing a transgene for anti-VEGF fab (Dose 2); Other Names: Combination Product
Experimental: RGX-314 Treatment Arm (Dose 3); RGX-314 Dose 3	Genetic: RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Names: Combination Product
Experimental: RGX-314 Treatment Arm (Dose 3) and Local Steroid; RGX-314 Dose 3 and Local Steroid	Genetic: RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Names: Combination Product; Drug: Local steroid; Local Steroid
Experimental: RGX-314 Treatment Arm (Dose 3) and Topical Steroid; RGX-314 Dose 3 and Topical Steroid	Genetic: RGX-314 Dose 3; AAV8 vector containing a transgene for anti-VEGF fab (Dose 3); Other Names: Combination Product; Drug: Topical steroid; Topical steroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the mean change in Best Corrected Visual Acuity (BCVA) for RGX-314 compared with ranibizumab monthly.	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
Evaluate the safety and tolerability of RGX-314	Incidence of overall and ocular adverse events (AEs) and serious adverse events (SAEs)	52 weeks
Evaluate the incidence of ocular inflammation following administration of RGX-314	Proportion of participants who experience ocular inflammation following SCS RGX-314 administration	52 weeks
Evaluate the effect of RGX-314 on choroidal neovascularization (CNV) lesion growth and leakage	Mean change from baseline in CNV lesion size and leakage area based on fluorescein angiography (FA) at Week 52.	52 weeks
Evaluate the effect of RGX-314 on BCVA	Mean change from baseline in BCVA to Week 52	52 weeks
Evaluate the effect of RGX-314 on central retinal thickness (CRT)	Mean change from baseline in CRT as measured by spectral domain-optical coherence tomography (SD-OCT) to Week 40 and Week 52	52 weeks
Assess the need for supplemental anti-vascular endothelial growth factor (VEGF) therapy in participants who receive RGX-314 treatment	Mean supplemental anti-VEGF injection annualized rate in the RGX-314 treatment arm through Week 40 and Week 52	52 weeks
Evaluate the concentration of RGX-314 transgene product (TP) in aqueous humor and serum	Mean change from baseline and Week 54 in serum RGX-314 TP concentration over time	52 weeks

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): January 1, 2024

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): May 22, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: AMD; wet AMD; wAMD; nAMD
• Additional Relevant MeSH Terms: Eye Diseases; Eye Abnormalities; Retinal Degeneration; Retinal Diseases; Uveal Diseases; Choroid Diseases; Macular Degeneration; Wet Macular Degeneration; Choroidal Effusions; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: RGX-314-2102

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