Safety and Tolerability of RGX-314 (Investigational Product) Gene Therapy for Neovascular AMD Trial

May 12, 2023 updated by: REGENXBIO Inc.

A Phase I/IIa (Phase 1/Phase 2a), Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of Gene Therapy With RGX-314 in Subjects With Neovascular AMD (nAMD)

Excessive vascular endothelial growth factor (VEGF) plays a key part in promoting neovascularization and edema in neovascular (wet) age-related macular degeneration (nAMD). VEGF inhibitors (anti-VEGF), including ranibizumab (LUCENTIS®, Genentech) and aflibercept (EYLEA®, Regeneron), have been shown to be safe and effective for treating nAMD and have demonstrated improvement in vision. However, anti-VEGF therapy is administered frequently via intravitreal injection and can be a significant burden to the patients. RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein. The long-term, stable delivery of this therapeutic protein following a 1 time gene therapy treatment for nAMD could potentially reduce the treatment burden of currently available therapies while maintaining vision with a favorable benefit:risk profile.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This Phase I/IIa, open-label, multiple-cohort, dose-escalation study was designed to evaluate the safety and tolerability of RGX-314 gene therapy in subjects with previously treated nAMD. Five doses were studied in approximately 42 subjects. Subjects who met the inclusion/exclusion criteria and had an anatomic response to an initial anti-VEGF injection received a single dose of RGX-314 administered by subretinal delivery. RGX-314 uses an AAV8 vector that contains a gene that encodes for a monoclonal antibody fragment which binds to and neutralizes VEGF activity. Safety was the primary focus for the initial 24 weeks after RGX-314 administration (primary study period). Following completion of the primary study period, subjects continued to be assessed until 104 weeks following treatment with RGX-314.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

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
    • California
      • Santa Barbara, California, United States, 93103
        • Santa Barbara Location
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Baltimore Location
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Boston Location
    • Nevada
      • Reno, Nevada, United States, 89502
        • Reno Location
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Philadelphia location 1
      • Philadelphia, Pennsylvania, United States, 19107
        • Philadelphia location 2
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Memphis location
    • Texas
      • Houston, Texas, United States, 77030
        • Houston location

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

46 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients ≥ 50 and ≤ 89 years with a diagnosis of subfoveal CNV (Choroidal neovascularization) secondary to AMD in the study eye receiving prior intravitreal anti-VEGF therapy.
  2. BCVA (Best Corrected Visual Acuity) between ≤20/63 and ≥20/400 (≤63 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/40 and ≥20/400 (≤73 and ≥19 ETDRS letters) for the rest of the cohort.
  3. History of need for and response to anti-VEGF therapy.
  4. Response to anti-VEGF at trial entry (assessed by SD-OCT (Spectral Domain Optical Coherence Tomography) at week 1)
  5. Must be pseudophakic (status post cataract surgery) in the study eye.
  6. AST (Aspartate aminotransferase)/ALT (Alanine aminotransferase) < 2.5 × ULN (Upper limit of normal); TB (Total bilirubin) < 1.5 × ULN; PT (Prothrombin time) < 1.5 × ULN; Hb > 10 g/dL (males) and > 9 g/dL (females); Platelets > 100 × 10^3/µL; eGFR (Estimated glomerular filtration rate) > 30 mL/min/1.73 m^2
  7. Must be willing and able to provide written, signed informed consent.

Exclusion Criteria:

  1. CNV or macular edema in the study eye secondary to any causes other than AMD.
  2. Any condition preventing visual acuity improvement in the study eye, eg, fibrosis, atrophy, or retinal epithelial tear in the center of the fovea.
  3. Active or history of retinal detachment in the study eye.
  4. Advanced glaucoma in the study eye.
  5. History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening.
  6. Presence of an implant in the study eye at screening (excluding intraocular lens).
  7. Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within the past 6 months.
  8. Uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100 mmHg) despite maximal medical treatment.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
3E9 GC (genome copies)/eye of RGX-314 (E means the exponential constant)
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Cohort 2
1E10 GC/eye of RGX-314
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Cohort 3
6E10 GC/eye of RGX-314
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Cohort 4
1.6E11 GC/eye of RGX-314
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein
Experimental: Cohort 5
2.5E11 GC/eye of RGX-314
Genetic: RGX-314
RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))
Time Frame: 26 weeks (24 weeks following RGX-314 administration)
Participants with ocular and non-ocular AEs and SAEs through 26 weeks (24 weeks following RGX-314 administration)
26 weeks (24 weeks following RGX-314 administration)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety (Participants With Ocular and Non-ocular AEs and SAEs)
Time Frame: 106 weeks (104 weeks following RGX-314 administration)
Participants with ocular and non-ocular AEs and SAEs
106 weeks (104 weeks following RGX-314 administration)
Change From Baseline in BCVA (Best Corrected Visual Acuity)
Time Frame: 106 weeks (104 weeks following RGX-314 administration)
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.
106 weeks (104 weeks following RGX-314 administration)
Change From Baseline in CRT (Central Retinal Thickness)
Time Frame: 106 weeks (104 weeks following RGX-314 administration)
Retinal fluid status of the study eye was evaluated using spectral domain OCT (Optical Coherence Tomography). A decrease in value indicates a decrease in fluid
106 weeks (104 weeks following RGX-314 administration)
Supplemental Injections (Annualized Rate of Supplemental Injections)
Time Frame: 106 weeks (104 weeks following RGX-314 administration)
The number of supplemental anti-VEGF injections given after RGX-314 was administered. Injections per year which were determined by the number of supplemental injections divided total follow-up in study days which is annualized to a per year rate. Injections were given for signs of worsening disease at a study visit, per the discretion of the investigator.
106 weeks (104 weeks following RGX-314 administration)
Mean Change From Baseline in Area of CNV (Choroidal Neovascularization)
Time Frame: 106 weeks (104 weeks following RGX-314 administration)
Area of Choroidal Neovascularization of the study eye was assessed with color fundus photography. Analysis was performed by the central reading center. An increase in value represents an increase in CNV.
106 weeks (104 weeks following RGX-314 administration)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
REGENXBIO Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jeffrey Heier, MD, Ophthalmic Consultants of Boston

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 29, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 24, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 17, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 17, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 28, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 16, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RGX-314-001

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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Conditions

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