Phase 2 Trial of RGX-314 in Adults With Center Involved - Diabetic Macular Edema (CI - DME)

Official title

A Randomized, Open Label, Controlled, Phase 2 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 AAV Gene Therapy Administered Via Subretinal Delivery in Participants With Center Involved Diabetic Macular Edema

Overview

Phase 2 open label, randomized, active controlled, dose-ranging trial in adults with Center Involved - Diabetic Macular Edema (CI - DME)

Detailed description

This Phase 2 trial is an open label, randomized, active controlled, dose-ranging trial to allow for preliminary safety and efficacy data on subretinal (SR) delivery of RGX-314 in participants with CI - DME

Interventions

• Genetic RGX-314 Dose 1
  AAV8 vector containing a transgene for anti-VEGF fab (Dose 1)
• Genetic RGX-314 Dose 2
  AAV8 vector containing a transgene for anti-VEGF fab (Dose 2)
• Biological Aflibercept (2.0 mg)
  Commercially available Active Comparator

Primary outcome measures

• Mean change from baseline in BCVA in the study eye at Week 52 [Time frame: 52 Weeks]

Secondary outcome measures (12)

• Mean change from baseline in BCVA in the study eye over time [Time frame: 52 Weeks]
• Proportion of participants with BCVA of 20/40 or better (ETDRS ≥ 69 letters) in the study eye over time [Time frame: 52 Weeks]
• Mean change from baseline in central subfield thickness (CST) in the study at week 52 [Time frame: 52 Weeks]
• Mean change from baseline in CST in the study eye on SD-OCT at Week 26 and Week 52 [Time frame: 52 Weeks]
• Proportion of participants with an absence of CI-DME in the study eye at Week 26 and Week 52 [Time frame: 52 Weeks]
• Proportion of participants achieving a 2-step or greater improvement or any improvement (a 1-step or greater improvement) in DR in the study eye by ETDRS DRSS on 4 widefield digital stereoscopic fundus photography at Week 52 [Time frame: 52 Weeks]
• Incidences of overall and ocular adverse events (AEs) [Time frame: 52 Weeks]
• Proportion of participants requiring any additional intervention for ocular diabetic complications to Week 52 [Time frame: 52 Weeks]
• Proportion of participants with any sight-threatening ocular diabetic complications to Week 52 [Time frame: 52 Weeks]
• Proportion of participants developing ocular diabetic complications requiring treatment per standard of care (anti-VEGF treatment, steroid treatment, pan retinal photocoagulation, laser, or surgery) through Week 52 [Time frame: 52 Weeks]
• Proportion of participants developing ocular diabetic complications (e.g., neovascularization due to DR) requiring treatment per standard of care (pan retinal photocoagulation or anti-VEGF treatment) through Week 52 [Time frame: 52 Weeks]
• Proportion of participants developing ocular diabetic complications (e.g., retinal detachments) requiring surgical intervention per standard of care through Week 52 [Time frame: 52 Weeks]

Eligibility criteria

Inclusion criteria

• Type I or Type II diabetes mellitus with center involving diabetic macular edema with previous treatment
• HbA1c ≤12%
• BCVA in study eye 78 to 25 ETDRS letters (\~20/32 to 20/320) at screening
• Decreased visual acuity attributable primarily due to CI - DME
• Demonstrate clinical response to aflibercept injection in the study eye
• Provide written informed consent

Exclusion criteria

• Women of childbearing potential
• Neovascularization in the study eye from a cause other than DR
• Evidence in the study eye of optic nerve pallor on clinical examination
• History of pan retinal photocoagulation in the study eye
• Any concurrent ocular condition in the study eye other than CI-DME that could require surgical intervention within 6 months or any condition in the study eye that may increase the risk to the participant, require either medical or surgical intervention during the study to prevent or treat vision loss, or interfere with the study procedures or assessments
• Presence of an implant in the study eye at screening (excluding intraocular lens)
• Any condition in the investigator's opinion that could limit VA improvement in the study eye
• Active or history of glaucoma, steroid response, or ocular hypertension
• Any prior intravitreal steroid injection in the study eye within 6 months prior to screening, administration in the study eye of Ozudrex® within 12 months prior to screening, or administration in the study eye if Iluven® within 36 months prior to screening
• Diabetic macular edema diagnosis ≥ 7 years
• History of chronic renal failure requiring dialysis or kidney transplant
• Participation in any other gene therapy study or receipt of any investigational product within 30 days prior to enrollment or 5 half-lives of the investigational product, whichever is longer, or any plans to use an investigational product within 6 months following enrollment

Note: Other inclusion/exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Sierra Eye Associates — Reno

Identifiers

NCT: NCT06942520 · SEA1979

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗