Diabetic Retinopathy (DR) is a common eye condition caused by diabetes, where high blood sugar levels damage the blood vessels in the back part of the eye (called the retina). Over time, this damage can lead to vision problems and even blindness if not treated. This study will assess surabgene lomparvovec (sura-vec) as a potential one-time gene therapy administered in the suprachoroidal space (SCS) for the treatment of diabetic retinopathy (DR) and prevention of vision-threatening events (VTEs) in participants with non-proliferative DR (NPDR) without center-involved diabetic macular edema (CI-DME).
This study will consist of 3 portions: a Phase 2b portion, a Phase 3 portion, and a bilateral treatment portion. Approximately 576 adult participants will be enrolled in the study across multiple sites in the United States and Puerto Rico.
In the Phase 2b and Phase 3 portions, participants will be randomized to different groups to receive sura-vec and prophylactic steroids or sham and artificial tears in their study eye. If assigned to sham, participants will be given an opportunity to cross over and receive treatment with sura-vec. In the bilateral treatment portion, participants will be enrolled to receive sura-vec and prophylactic steroids in both eyes. In all 3 portions, follow-up in the study will continue through 5 years following administration of sura-vec in each eye.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Moderately severe or severe nonproliferative diabetic retinopathy (NPDR) (early treatment diabetic retinopathy study-diabetic retinopathy severity scale [DRSS] level 47 or 53) for which panretinal photocoagulation (PRP) or anti- vascular endothelial growth factor (VEGF) can be safely deferred for at least 6 months after Screening Visit 1.
Best-corrected visual acuity (BCVA) in the study eye of >= 69 Early treatment diabetic retinopathy study letters (approximate Snellen equivalent 20/40 or better) at Screening Visit 1.
Active ocular inflammation including scleral inflammation (including episcleritis) or ocular/ periocular infection present in either eye at Screening Visit 1 or Screening Visit 2
Neovascularization from a cause other than DR, per investigator
Evidence or documented history of panretinal photocoagulation (PRP) or retinal laser therapy
History of intravitreal therapy, including anti-VEGF and long- or short-acting steroid therapy, within the prior 6 months and documentation of more than 10 prior anti-VEGF or short acting steroid intravitreal injections within 36 months of Screening Visit 1
Parallel
Surabgene Lomparvovec
DrugSolution Injection
Sham
Drugneedleless injection without fluid
Topical Steroid
DrugTopical Drops
Artificial Tears
DrugTopical Drops
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Treatment groupsSee each treatment group below.
Phase 2B: Percentage of Participants Achieving >= 2-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye
The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity.
Phase 3: Percentage of Participants Achieving >= 2-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye
The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity.
Bilateral Portion: Bilateral portion: Number of participants experiencing ocular Adverse Events (AEs), Serious Adverse Events (SAEs), or any Adverse Events of Special Interest (AESIs)
Safety of bilateral administration with sura-vec will be assessed with Ocular AEs, SAEs, and AESIs. An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Bilateral Portion: Participants Who Experience Intraocular Inflammation
Percentage of participants who experience intraocular inflammation.
Phase 2B: Percentage of Participants Who Develop a Vision-Threatening Event (VTE) due to Diabetic Retinopathy (DR)
Participants will be assessed for the development of VTEs
Phase 2B: Percentage of Participants Who Develop a Vision-Threatening Event (VTE) due to Diabetic Retinopathy (DR)
Participants will be assessed for the development of VTEs
Phase 2B: Percentage of Participants Who Experience Progression to Proliferative Diabetic Retinopathy (PDR) or Anterior Segment Neovascularization (ASNV) in the Study Eye
Participants will be assessed for the progression to PDR or ASNV.
Phase 2B: Percentage of Participants Who Experience Progression to Proliferative Diabetic Retinopathy (PDR) or Anterior Segment Neovascularization (ASNV) in the Study Eye
Participants will be assessed for the progression to PDR or ASNV.
