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Safety and Tolerability of RGX-314 Gene Therapy for Neovascular AMD Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03066258
Recruitment Status : Active, not recruiting
First Posted : February 28, 2017
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Regenxbio Inc.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Neovascular Age-related Macular Degeneration Wet Age-related Macular Degeneration Genetic: RGX-314 Phase 1 Phase 2

Detailed Description:
This Phase I/IIa, open-label, multiple-cohort, dose-escalation study is designed to evaluate the safety and tolerability of RGX-314 gene therapy in subjects with previously treated nAMD. Five doses will be studied in approximately 42 subjects. Subjects who meet the inclusion/exclusion criteria and have an anatomic response to an initial anti VEGF injection will receive 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 will be the primary focus for the initial 24 weeks after RGX-314 administration (primary study period). Following completion of the primary study period, subjects will continue to be assessed until 104 weeks following treatment with RGX-314.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIa, 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)
Actual Study Start Date : March 31, 2017
Actual Primary Completion Date : November 24, 2019
Estimated Study Completion Date : May 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose 1
3E9 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: Dose 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: Dose 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: Dose 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: Dose 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


Outcome Measures
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Primary Outcome Measures :
  1. Safety (incidence of ocular and non-ocular AEs and SAEs) [ Time Frame: 26 weeks ]
    incidence of ocular and non-ocular AEs and SAEs


Secondary Outcome Measures :
  1. Safety (incidence of ocular and non-ocular AEs and SAEs) [ Time Frame: 106 weeks ]
    incidence of ocular and non-ocular AEs and SAEs

  2. Change in best corrected visual acuity [ Time Frame: 106 weeks ]
    BCVA

  3. Change in central retinal thickness [ Time Frame: 106 weeks ]
    CRT as measured by SD-OCT

  4. Rescue injections (Mean number of rescue injections) [ Time Frame: 106 weeks ]
    Mean number of rescue injections

  5. Mean change in area of CNV [ Time Frame: 106 weeks ]
    Area of CNV and leakage measured by FA


Eligibility Criteria
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Ages Eligible for Study:   50 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients ≥ 50 and ≤ 89 years with a diagnosis of subfoveal CNV secondary to AMD in the study eye receiving prior intravitreal anti-VEGF therapy.
  2. BCVA 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 at week 1)
  5. Must be pseudophakic (status post cataract surgery) in the study eye.
  6. AST/ALT < 2.5 × ULN; TB < 1.5 × ULN; PT < 1.5 × ULN; Hb > 10 g/dL (males) and > 9 g/dL (females); Platelets > 100 × 10^3/µL; eGFR > 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03066258


Locations
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United States, California
Santa Barbara location
Santa Barbara, California, United States, 93103
United States, Maryland
Baltimore location
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston location
Boston, Massachusetts, United States, 02114
United States, Nevada
Reno location
Reno, Nevada, United States, 89502
United States, Pennsylvania
Philadelphia location 1
Philadelphia, Pennsylvania, United States, 19104
Philadelphia location 2
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Memphis location
Germantown, Tennessee, United States, 38138
United States, Texas
Houston location
Houston, Texas, United States, 77030
Sponsors and Collaborators
Regenxbio Inc.
Investigators
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Principal Investigator: Jeffrey Heier, MD Ophthalmic Consultants of Boston
More Information
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Responsible Party: Regenxbio Inc.
ClinicalTrials.gov Identifier: NCT03066258    
Other Study ID Numbers: RGX-314-001
First Posted: February 28, 2017    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regenxbio Inc.:
nAMD
wet AMD
gene therapy
Additional relevant MeSH terms:
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Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases