RGX-314 Gene Therapy Pharmacodynamic Study for Neovascular Age-related Macular Degeneration (nAMD)

September 3, 2024 updated by: AbbVie

A Phase 2, Open-label Study to Explore the Pharmacodynamics of Two Doses in Two Formulations of RGX-314 Gene Therapy Administered Via Subretinal Delivery in Participants With Neovascular Age-related Macular Degeneration

RGX-314 is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (nAMD) also referred to as Wet AMD. Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. The purpose of this phase 2, open label study is to evaluate whether different doses of RGX-314 from two different formulations (clinical versus eventual commercial formulation) perform the same in humans when delivered by subretinal administration

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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 repeated intraocular injections to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time. RGX-314 is being developed as a potential one-time treatment for wet AMD. RGX-314 uses an AAV8 vector that contains a gene that encodes for a monoclonal antibody fragment which binds to and neutralizes VEGF activity. This phase 2, open label study will explore the pharmacodynamics of two doses in two formulations of RGX-314 gene therapy via subretinal delivery in patients with neovascular Age-related Macular Degeneration. Approximately 60 patients (15 per cohort) who meet the inclusion/exclusion criteria will be enrolled in 4 sequential dose cohorts. A dose cohort will be comprised of 1 of 2 doses of RGX-314 in 1 of 2 formulations in order to explore the pharmacodynamics of RGX-314 based on aqueous humor transgene product (TP) concentrations. If the participants meet the study criteria and choose to participate in the study, their participation in the study will last about 12 months.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85014
        • Retinal Consultants of Arizona
      • Sun City, Arizona, United States, 85351
        • Barnet Dulaney Perkins Eye Center
    • California
      • San Diego, California, United States, 92064
        • Retina Consultants of San Diego
      • Santa Barbara, California, United States, 93103
        • California Retina Consultants
    • Florida
      • Saint Petersburg, Florida, United States, 33711
        • Retina Vitreous Associates of Florida
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Wilmer Eye Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Ophthalmic Consultants of Boston
    • Nevada
      • Reno, Nevada, United States, 89502
        • Sierra Eye Associates
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Eye Associates of New Mexico
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Wills Eye Hospital
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Charles Retina Institute
    • Texas
      • Dallas, Texas, United States, 75231
        • Texas Retina Associates
      • The Woodlands, Texas, United States, 77384
        • Retina Consultants of Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Males or females, aged ≥ 50 years and ≤ 89 years.
  2. An Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA-letter score between ≤ 78 and ≥ 40 in the study eye at Screening.
  3. Diagnosis of choroidal neovascularization (CNV) secondary to age-related macular degeneration in the study eye previously treated with anti-VEGF.
  4. Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry.
  5. Willing and able to provide written, signed informed consent for this study.
  6. Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye.

Exclusion Criteria:

  1. CNV or macular edema in the study eye secondary to any causes other than AMD.
  2. Subfoveal fibrosis or atrophy in study eye.
  3. Any condition in the investigator's opinion that could limit visual acuity improvement in the study eye.
  4. Active or history of retinal detachment or retinal tear in the study eye.
  5. Advanced glaucoma in the study eye.
  6. Prior treatment with gene therapy.
  7. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Commercial Formulation Dose 1
Dose 1 of RGX-314
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Clinical Formulation Dose 1
Dose 1 of RGX-314
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Commercial Formulation Dose 2
Dose 2 of RGX-314
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Clinical Formulation Dose 2
Dose 2 of RGX-314
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
RGX-314 target protein concentration in aqueous humor
Time Frame: At Week 24
At Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of ocular Adverse Events (AEs) and overall AEs
Time Frame: Through Week 48
Evaluate the safety and tolerability of RGX-314
Through Week 48
Changes in Best Corrected Visual Acuity (BCVA)
Time Frame: At Week 24 and 48
BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
At Week 24 and 48
Changes in Central Retinal Thickness (CRT)
Time Frame: At Week 24 and 48
CRT is measured by spectral domain optical coherence tomography (SD-OCT)
At Week 24 and 48
Mean Supplemental anti-VEGF injection annualized rate through week 24 and week 48
Time Frame: Through Week 24 and week 48
To assess the need for supplemental anti-VEGF therapy over 48 weeks
Through Week 24 and week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 22, 2021

Primary Completion (Actual)

October 2, 2023

Study Completion (Actual)

March 18, 2024

Study Registration Dates

First Submitted

March 30, 2021

First Submitted That Met QC Criteria

April 1, 2021

First Posted (Actual)

April 6, 2021

Study Record Updates

Last Update Posted (Estimated)

September 5, 2024

Last Update Submitted That Met QC Criteria

September 3, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RGX-314-2103

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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