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Neovascular Age-related Macular DegenerationPhase 1/2NCT03066258

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

A Phase 1/2 study testing RGX-314 in people with Neovascular Age-related Macular Degeneration and Wet Age-related Macular Degeneration, run by REGENXBIO Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 50 to 89 years
What is being tested?
RGX-314
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
8 sitesUnited States
Study dates
29 Mar 2017to 17 Jun 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 89 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Baltimore location

    Baltimore, Maryland, 21287

  • Boston location

    Boston, Massachusetts, 02114

  • Memphis location

    Germantown, Tennessee, 38138

  • Houston location

    Houston, Texas, 77030

  • Philadelphia location 1

    Philadelphia, Pennsylvania, 19104

  • Philadelphia location 2

    Philadelphia, Pennsylvania, 19107

  • Reno location

    Reno, Nevada, 89502

  • Santa Barbara location

    Santa Barbara, California, 93103

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
RGX-314
Keywords
nAMD, wet AMD, gene therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RGX-314Genetic

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

Study groups in NCT03066258
Study groupRoleWhat they receive
Cohort 1Experimental3E9 GC (genome copies)/eye of RGX-314 (E means the exponential constant)
Receives: Genetic: RGX-314
Cohort 2Experimental1E10 GC/eye of RGX-314
Receives: Genetic: RGX-314
Cohort 3Experimental6E10 GC/eye of RGX-314
Receives: Genetic: RGX-314
Cohort 4Experimental1.6E11 GC/eye of RGX-314
Receives: Genetic: RGX-314
Cohort 5Experimental2.5E11 GC/eye of RGX-314
Receives: Genetic: RGX-314

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 26 weeks (24 weeks following RGX-314 administration)

Secondary outcomes (5)

  1. Safety (Participants With Ocular and Non-ocular AEs and SAEs)

    Participants with ocular and non-ocular AEs and SAEs

    Measured: 106 weeks (104 weeks following RGX-314 administration)

  2. Change From Baseline in BCVA (Best Corrected Visual Acuity)

    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.

    Measured: 106 weeks (104 weeks following RGX-314 administration)

  3. Change From Baseline in CRT (Central Retinal Thickness)

    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

    Measured: 106 weeks (104 weeks following RGX-314 administration)

  4. Supplemental Injections (Annualized Rate of Supplemental Injections)

    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.

    Measured: 106 weeks (104 weeks following RGX-314 administration)

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

    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.

    Measured: 106 weeks (104 weeks following RGX-314 administration)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2017
  2. Study start29 Mar 2017
  3. Primary completion24 Nov 2019
  4. Study completion17 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
dose escalation
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03066258
Sponsor's protocol ID
RGX-314-001
Status last verified
May 2023
First submitted
17 Feb 2017
Last updated
16 May 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38554726

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RGX-314 in people with Neovascular Age-related Macular Degeneration and Wet Age-related Macular Degeneration, run by REGENXBIO Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03066258, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2023.

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