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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.

Tracking Information
First Submitted Date  ICMJE February 17, 2017
First Posted Date  ICMJE February 28, 2017
Last Update Posted Date October 8, 2020
Actual Study Start Date  ICMJE March 31, 2017
Actual Primary Completion Date November 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2017)
Safety (incidence of ocular and non-ocular AEs and SAEs) [ Time Frame: 26 weeks ]
incidence of ocular and non-ocular AEs and SAEs
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2017)
  • Safety (incidence of ocular and non-ocular AEs and SAEs) [ Time Frame: 106 weeks ]
    incidence of ocular and non-ocular AEs and SAEs
  • Change in best corrected visual acuity [ Time Frame: 106 weeks ]
    BCVA
  • Change in central retinal thickness [ Time Frame: 106 weeks ]
    CRT as measured by SD-OCT
  • Rescue injections (Mean number of rescue injections) [ Time Frame: 106 weeks ]
    Mean number of rescue injections
  • Mean change in area of CNV [ Time Frame: 106 weeks ]
    Area of CNV and leakage measured by FA
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability of RGX-314 Gene Therapy for Neovascular AMD Trial
Official Title  ICMJE 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)
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neovascular Age-related Macular Degeneration
  • Wet Age-related Macular Degeneration
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Dose 1
    3E9 GC/eye of RGX-314
    Intervention: Genetic: RGX-314
  • Experimental: Dose 2
    1E10 GC/eye of RGX-314
    Intervention: Genetic: RGX-314
  • Experimental: Dose 3
    6E10 GC/eye of RGX-314
    Intervention: Genetic: RGX-314
  • Experimental: Dose 4
    1.6E11 GC/eye of RGX-314
    Intervention: Genetic: RGX-314
  • Experimental: Dose 5
    2.5E11 GC/eye of RGX-314
    Intervention: Genetic: RGX-314
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2019)
42
Original Estimated Enrollment  ICMJE
 (submitted: February 22, 2017)
18
Estimated Study Completion Date  ICMJE May 2021
Actual Primary Completion Date November 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03066258
Other Study ID Numbers  ICMJE RGX-314-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Regenxbio Inc.
Study Sponsor  ICMJE Regenxbio Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey Heier, MD Ophthalmic Consultants of Boston
PRS Account Regenxbio Inc.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP