RGX-314 Gene Therapy Administered in the Suprachoroidal Space for Participants With Diabetic Retinopathy (DR) Without Center Involved-Diabetic Macular Edema (CI-DME) (ALTITUDE)

May 18, 2023 updated by: AbbVie

A Phase 2, Randomized, Dose-escalation, Observation-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of RGX-314 Gene Therapy Delivered Via a Single Suprachoroidal Space (SCS) Injections in Participants With Diabetic Retinopathy (DR) Without Center Involved-Diabetic Macular Edema (CI-DME)(ALTITUDE)

RGX-314 is being developed as a novel, potential one-time gene therapy treatment for the treatment of diabetic retinopathy, a chronic and progressive complication of diabetes mellitus. Diabetic retinopathy (DR) is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that leads to further deterioration of functional vision. Despite the availability of current treatments, diabetic retinopathy remains the leading cause of vision loss in working-age adults, those between the ages of 20 and 74. Existing treatment with anti-VEGF agents, although shown to be effective, are limited by short therapeutic half-lives, which then require frequent intravitreal injections over the patient's lifetime, resulting in increased risk of associated adverse events and significant treatment burden. Due to the burden of treatment, patients often do not closely adhere to treatment regimens and experience sub-optimal outcomes and a decline in vision. RGX-314 is being developed as a potential one time treatment for diabetic retinopathy, which may deliver advantages over conventional treatments, such as potentially providing a longer duration of therapeutic effect and intervening at an earlier stage of the disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of RGX-314 gene therapy in subjects with DR without center-involved diabetic macular edema (CI-DME). Approximately 100 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 5 cohorts. Participants will be randomized in Cohorts 1, 2, 4 and 5 to receive RGX-314 or to be observed, and participants enrolled in Cohorts 3 will receive RGX-314. Cohort 1 will evaluate RGX-314 Dose 1, Cohorts 2 and 3 will evaluate RGX-314 Dose 2, Cohorts 4 and 5 will evaluate RGX-314 Dose 3. Following SCS RGX-314 administration, participants in Cohorts 4 and 5 will receive a protocol-mandated post-procedure steroid regimen for 7 weeks. Participants who are randomized to be observed in Cohorts 1, 2, 4 and 5 will be offered RGX-314 after completing the study. Efficacy will be the primary focus of the study. Participants will be evaluated for safety and tolerability of RGX-314 throughout the study.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85014
        • Recruiting
        • Retinal Research Institute, LLC
        • Principal Investigator:
          • Phoenix Site PI
    • California
      • Bakersfield, California, United States, 93309
        • Recruiting
        • California Retina Consultants
        • Principal Investigator:
          • Bakersfield Site PI
      • Beverly Hills, California, United States, 90017
        • Recruiting
        • Retina-Vitreous Associates Medical Group
        • Principal Investigator:
          • Beverly Hills Site PI
      • Campbell, California, United States, 95008
        • Recruiting
        • Retinal Diagnostic Center
        • Principal Investigator:
          • Campbell Site PI
      • Mountain View, California, United States, 94040
        • Recruiting
        • Northern California Retina Vitreous Associates Medical Group, Inc.
        • Principal Investigator:
          • Mountain View Site PI
      • Pasadena, California, United States, 91107
        • Recruiting
        • California Eye Specialists Medical Group, Inc
        • Principal Investigator:
          • Pasadena Site PI
      • Poway, California, United States, 92064
        • Recruiting
        • Retinal Consultants San Diego
        • Principal Investigator:
          • Poway Site PI
      • Santa Barbara, California, United States, 93103
        • Recruiting
        • California Retina Consultants
        • Principal Investigator:
          • Santa Barbara Site PI
    • Georgia
      • Augusta, Georgia, United States, 30909
        • Recruiting
        • Southeast Retina Center, PC
        • Principal Investigator:
          • Augusta Site PI
    • Illinois
      • Oak Forest, Illinois, United States, 60452
        • Recruiting
        • University Retina and Macula Associates, PC
        • Principal Investigator:
          • Oak Forest Site PI
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Wilmer Eye Institute/Johns Hopkins University School of Medicine
        • Principal Investigator:
          • Baltimore Site PI
      • Hagerstown, Maryland, United States, 21740
        • Recruiting
        • Cumberland Valley Retina Consultants
        • Principal Investigator:
          • Hagerstown Site PI
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Ophthalmic Consultants of Boston
        • Principal Investigator:
          • Boston Site PI
    • Nevada
      • Reno, Nevada, United States, 89502
        • Recruiting
        • Sierra Eye Associates
        • Principal Investigator:
          • Reno Site PI
    • New Jersey
      • Teaneck, New Jersey, United States, 07666
        • Recruiting
        • NJ Retina
        • Principal Investigator:
          • Teaneck Site PI
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Recruiting
        • Vision Research Center Eye Associates of New Mexico
        • Principal Investigator:
          • Albuquerque Site PI
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University Eye Center
        • Principal Investigator:
          • Durham Site PI
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Mid Atlantic Retina
        • Principal Investigator:
          • Philadelphia Site PI
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Recruiting
        • Charles Retina Institute, P.C.
        • Principal Investigator:
          • Germantown Site PI
    • Texas
      • Austin, Texas, United States, 78750
        • Recruiting
        • Austin Clinical Research, LLC
        • Principal Investigator:
          • Austin Site PI
      • The Woodlands, Texas, United States, 77384
        • Recruiting
        • Retinal Consultants of Texas
        • Principal Investigator:
          • Woodlands Site PI

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

Ages Eligible for Study

25 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients 25-89 years of age with a diabetic retinopathy diagnosis of nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) secondary to diabetes mellitus Type 1 or 2 for which PRP or anti-VEGF injections can be safely deferred for at least 6 months
  • Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)
  • Prior history of CI-DME in the study eye is acceptable.
  • Must be willing and able to provide written, signed informed consent.

Exclusion Criteria:

  • Neovascularization in the study eye from a cause other than DR.
  • Presence of any active CI-DME.
  • Active or history of retinal detachment in the study eye.
  • Any evidence or documented history of PRP or retinal laser in the study eye.
  • Patients who had a prior vitrectomy surgery.
  • Women of childbearing potential.

Note: Other inclusions/exclusions criteria apply

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RGX-314 Treatment Arm (Dose 1)
RGX-314 Dose 1
Genetic: RGX-314 Dose 1
AAV8 vector containing a transgene for anti-VEGF fab (Dose 1)
Other Names:
  • Combination Product
Experimental: RGX-314 Treatment Arm (Dose 2)
RGX-314 Dose 2
Genetic: RGX-314 Dose 2
AAV8 vector containing a transgene for anti-VEGF fab (Dose 2)
Other Names:
  • Combination Product
Experimental: RGX-314 Treatment Arm (Dose 3) and Topical Steroid
RGX-314 Dose 3 and Topical Steroid
Genetic: RGX-314 Dose 3
AAV8 vector containing a transgene for anti-VEGF fab (Dose 3)
Other Names:
  • Combination Product
Drug: Topical Steroid
Topical Steroid
No Intervention: Observation Control Arm
Observation Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the effect of RGX-314 on DR by the Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (-DRSS) at week 48
Time Frame: 48 weeks
Proportion of participants achieving a 2-step or greater improvement in DR by Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (-DRSS) at Week 48 scored from Levels 10-85 with higher levels indicating greater DR severity.
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the effect of RGX-314 on DR (ETDRS-DRSS) over time
Time Frame: 48 weeks
Proportion of participants achieving improvement or worsening in DR per ETDRS-DRSS grading through week 48
48 weeks
To assess the safety and tolerability of RGX-314
Time Frame: 48 weeks
Assess the incidence of overall and ocular Adverse Events (AEs)
48 weeks
To evaluate the need for additional Standard of Care (SOC) intervention due to ocular vision-threatening diabetic complications
Time Frame: 48 weeks
Proportion of participants with sight-threatening ocular diabetic complications requiring additional SOC intervention (anti-VEGF, Pan-Retinal Photocoagulation (PRP), laser, steroids, or surgical intervention)
48 weeks
To evaluate the incidences of ocular inflammation following SCS RGX-314 administration
Time Frame: 48 weeks
Proportion of participants who experience ocular inflammation following SCS RGX-314 administration.
48 weeks

Collaborators and Investigators

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

Sponsor

AbbVie

Collaborators

AbbVie

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)

November 20, 2020

Primary Completion (Anticipated)

May 1, 2024

Study Completion (Anticipated)

October 1, 2024

Study Registration Dates

First Submitted

September 15, 2020

First Submitted That Met QC Criteria

September 23, 2020

First Posted (Actual)

September 28, 2020

Study Record Updates

Last Update Posted (Actual)

May 22, 2023

Last Update Submitted That Met QC Criteria

May 18, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RGX-314-2202

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

Yes

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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