NCT03066258

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Mar 2017

Longer than P75 for phase_1

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 17, 2017

Completed
11 days until next milestone

First Posted

Study publicly available on registry

February 28, 2017

Completed
29 days until next milestone

Study Start

First participant enrolled

March 29, 2017

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 24, 2019

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 17, 2021

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

May 16, 2023

Completed
Last Updated

May 16, 2023

Status Verified

May 1, 2023

Enrollment Period

2.7 years

First QC Date

February 17, 2017

Results QC Date

February 13, 2023

Last Update Submit

May 12, 2023

Conditions

Neovascular Age-related Macular DegenerationWet Age-related Macular Degeneration

Keywords

nAMDwet AMDgene therapy

Outcome Measures

Primary Outcomes (1)

  • Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))

    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 Outcomes (5)

  • Safety (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)

    106 weeks (104 weeks following RGX-314 administration)

  • Change From Baseline in CRT (Central Retinal Thickness)

    106 weeks (104 weeks following RGX-314 administration)

  • Supplemental Injections (Annualized Rate of Supplemental Injections)

    106 weeks (104 weeks following RGX-314 administration)

  • Mean Change From Baseline in Area of CNV (Choroidal Neovascularization)

    106 weeks (104 weeks following RGX-314 administration)

Study Arms (5)

Cohort 1

EXPERIMENTAL

3E9 GC (genome copies)/eye of RGX-314 (E means the exponential constant)

Genetic: RGX-314

Cohort 2

EXPERIMENTAL

1E10 GC/eye of RGX-314

Genetic: RGX-314

Cohort 3

EXPERIMENTAL

6E10 GC/eye of RGX-314

Genetic: RGX-314

Cohort 4

EXPERIMENTAL

1.6E11 GC/eye of RGX-314

Genetic: RGX-314

Cohort 5

EXPERIMENTAL

2.5E11 GC/eye of RGX-314

Genetic: RGX-314

Interventions

RGX-314GENETIC

RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein

Cohort 1Cohort 2Cohort 3Cohort 4Cohort 5

Eligibility Criteria

Age50 Years - 89 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.
  • History of need for and response to anti-VEGF therapy.
  • Response to anti-VEGF at trial entry (assessed by SD-OCT (Spectral Domain Optical Coherence Tomography) at week 1)
  • Must be pseudophakic (status post cataract surgery) in the study eye.
  • 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
  • Must be willing and able to provide written, signed informed consent.

You may not qualify if:

  • CNV or macular edema in the study eye secondary to any causes other than AMD.
  • Any condition preventing visual acuity improvement in the study eye, eg, fibrosis, atrophy, or retinal epithelial tear in the center of the fovea.
  • Active or history of retinal detachment in the study eye.
  • Advanced glaucoma in the study eye.
  • 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.
  • Presence of an implant in the study eye at screening (excluding intraocular lens).
  • Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within the past 6 months.
  • Uncontrolled hypertension (systolic blood pressure \[BP\] \>180 mmHg, diastolic BP \>100 mmHg) despite maximal medical treatment.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Santa Barbara location

Santa Barbara, California, 93103, United States

Location

Baltimore location

Baltimore, Maryland, 21287, United States

Location

Boston location

Boston, Massachusetts, 02114, United States

Location

Reno location

Reno, Nevada, 89502, United States

Location

Philadelphia location 1

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia location 2

Philadelphia, Pennsylvania, 19107, United States

Location

Memphis location

Germantown, Tennessee, 38138, United States

Location

Houston location

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • Campochiaro PA, Avery R, Brown DM, Heier JS, Ho AC, Huddleston SM, Jaffe GJ, Khanani AM, Pakola S, Pieramici DJ, Wykoff CC, Van Everen S. Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study. Lancet. 2024 Apr 20;403(10436):1563-1573. doi: 10.1016/S0140-6736(24)00310-6. Epub 2024 Mar 27.

    PMID: 38554726DERIVED

Results Point of Contact

Title
Sherri Van Everen, PharmD/ Vice President of Clinical Development
Organization
Regenxbio Inc.
svaneveren@regenxbio.com
240.552.8181

Study Officials

  • Jeffrey Heier, MD

    Ophthalmic Consultants of Boston

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: dose escalation
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 17, 2017

First Posted

February 28, 2017

Study Start

March 29, 2017

Primary Completion

November 24, 2019

Study Completion

June 17, 2021

Last Updated

May 16, 2023

Results First Posted

May 16, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will not share

Locations

US(8)