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

Diabetic Retinopathy (DR) Clinical Trial

— ALTITUDE  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04567550
• Other study ID #: RGX-314-2202
• Status: Recruiting
• Phase: Phase 2
• Start date: November 20, 2020
• Est. completion date: October 2024

Study information

• Verified date: May 2023
• Source: AbbVie
• Contact: Patient Advocacy
• Phone: 1-866-860-0117
• Email: patientadvocacy[@]regenxbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Choroidal Effusions
• Diabetic Retinopathy
• Diabetic Retinopathy (DR)
• Macular Edema
• Retinal Diseases

Intervention

Genetic:
• RGX-314 Dose 1
AAV8 vector containing a transgene for anti-VEGF fab (Dose 1)
• RGX-314 Dose 2
AAV8 vector containing a transgene for anti-VEGF fab (Dose 2)
• RGX-314 Dose 3
AAV8 vector containing a transgene for anti-VEGF fab (Dose 3)

Drug:
• Topical Steroid
Topical Steroid

Locations

Country	Name	City	State
United States	Vision Research Center Eye Associates of New Mexico	Albuquerque	New Mexico
United States	Southeast Retina Center, PC	Augusta	Georgia
United States	Austin Clinical Research, LLC	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Wilmer Eye Institute/Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Retinal Diagnostic Center	Campbell	California
United States	Duke University Eye Center	Durham	North Carolina
United States	Charles Retina Institute, P.C.	Germantown	Tennessee
United States	Cumberland Valley Retina Consultants	Hagerstown	Maryland
United States	Northern California Retina Vitreous Associates Medical Group, Inc.	Mountain View	California
United States	University Retina and Macula Associates, PC	Oak Forest	Illinois
United States	California Eye Specialists Medical Group, Inc	Pasadena	California
United States	Mid Atlantic Retina	Philadelphia	Pennsylvania
United States	Retinal Research Institute, LLC	Phoenix	Arizona
United States	Retinal Consultants San Diego	Poway	California
United States	Sierra Eye Associates	Reno	Nevada
United States	California Retina Consultants	Santa Barbara	California
United States	NJ Retina	Teaneck	New Jersey
United States	Retinal Consultants of Texas	The Woodlands	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	To evaluate the effect of RGX-314 on DR (ETDRS-DRSS) over time	Proportion of participants achieving improvement or worsening in DR per ETDRS-DRSS grading through week 48	48 weeks
Secondary	To assess the safety and tolerability of RGX-314	Assess the incidence of overall and ocular Adverse Events (AEs)	48 weeks
Secondary	To evaluate the need for additional Standard of Care (SOC) intervention due to ocular vision-threatening diabetic complications	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
Secondary	To evaluate the incidences of ocular inflammation following SCS RGX-314 administration	Proportion of participants who experience ocular inflammation following SCS RGX-314 administration.	48 weeks