Surabgene Lomparvovec Administered in the Suprachoroidal Space in Adult Participants With Diabetic Retinopathy Without Center-Involved Diabetic Macular Edema

Official title

An Operationally Seamless Phase 2b/3, Multicenter, Randomized, Masked, Sham-controlled Study to Evaluate the Efficacy and Safety of Surabgene Lomparvovec (Sura-vec) Delivered Via Suprachoroidal Space (SCS) Injection Targeting Subjects With Diabetic Retinopathy Without Center Involved-Diabetic Macular Edema (CI-DME) (NAAVIGATE)

Overview

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.

Interventions

• Drug Surabgene Lomparvovec
  Solution Injection
• Drug Sham
  needleless injection without fluid
• Drug Topical Steroid
  Topical Drops
• Drug Artificial Tears
  Topical Drops

Primary outcome measures

• Phase 2B: Percentage of Participants Achieving >= 2-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye [Time frame: At Week 52]
• Phase 3: Percentage of Participants Achieving >= 2-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye [Time frame: At Week 52]
• Bilateral Portion: Bilateral portion: Number of participants experiencing ocular Adverse Events (AEs), Serious Adverse Events (SAEs), or any Adverse Events of Special Interest (AESIs) [Time frame: Up to Approximately Week 104]
• Bilateral Portion: Participants Who Experience Intraocular Inflammation [Time frame: Up to Approximately Week 104]
• Bilateral Portion: Participants Who Experience Scleral Inflammation Including Episcleritis [Time frame: Up to Approximately Week 104]

Secondary outcome measures (12)

• Phase 2B: Percentage of Participants Who Develop a Vision-Threatening Event (VTE) due to Diabetic Retinopathy (DR) [Time frame: Up to Approximately Week 52]
• Phase 2B: Percentage of Participants Who Develop a Vision-Threatening Event (VTE) due to Diabetic Retinopathy (DR) [Time frame: Up to Approximately Week 104]
• Phase 2B: Percentage of Participants Who Experience Progression to Proliferative Diabetic Retinopathy (PDR) or Anterior Segment Neovascularization (ASNV) in the Study Eye [Time frame: Up to Approximately Week 52]
• Phase 2B: Percentage of Participants Who Experience Progression to Proliferative Diabetic Retinopathy (PDR) or Anterior Segment Neovascularization (ASNV) in the Study Eye [Time frame: Up to Approximately Week 104]
• Phase 2B: Percentage of Participants Who Develop Center Involved-Diabetic Macular Edema (CI-DME) in the Study Eye [Time frame: Up to Approximately Week 52]
• Phase 2B: Percentage of Participants Who Develop Center Involved-Diabetic Macular Edema (CI-DME) in the Study Eye [Time frame: Up to Approximately Week 104]
• Phase 2B: Percentage of Participants Achieving >= 2-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye [Time frame: At Week 104]
• Phase 2B: Participants Who Develop Treatment-Emergent Ocular Inflammation in the Study Eye. [Time frame: Up to approximately Week 14]
• Phase 2B: Participants Who Develop Treatment-Emergent Ocular Inflammation in the Study Eye. [Time frame: Up to approximately Week 24]
• Phase 2B: Participants Who Develop Treatment-Emergent Ocular Inflammation in the Study Eye. [Time frame: Up to approximately Week 38]
• Phase 2B: Participants Who Develop Treatment-Emergent Ocular Inflammation in the Study Eye. [Time frame: Up to approximately Week 52]
• Phase 2B: Percentage of Participants Achieving>= 2-Step Worsening from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye [Time frame: At Week 52]

Eligibility criteria

Inclusion criteria

Ocular (Study Eye for Phase 2b and Phase 3 Portions; Both Eyes for Bilateral Portion)

• 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.

Systemic

• Diabetic retinopathy (DR) secondary to diabetes mellitus Type 1 or 2 with a hemoglobin A1c (HbA1c)< 12% within 60 days prior to Screening Visit 1.

Exclusion criteria

Ocular (Study Eye for Phase 2b and Phase 3 Portions; Both Eyes for Bilateral Portion)

• Presence of active center involved-diabetic macular edema (CI-DME) in the study eye as determined by spectral domain optical coherence tomography (SD-OCT) evaluated by the central reading center (CRC), using the following threshold:

Central retinal thickness (CRT) >= 320 μm as measured by Heidelberg Spectralis SD-OCT (conversion to equivalent measurement is required and performed by the CRC if imaging is done with another SD-OCT instrument).

• 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
• Pregnant and breastfeeding individuals are excluded from this clinical study.

Systemic

• Initiation of intensive insulin treatment (pump or multiple daily injections) within the past 6 months or plans to do so within 52 weeks after Day 1
• Initiation of any treatment containing a GLP-1 receptor agonist within the 3 months prior to Screening Visit 1 or plans to do so within 52 weeks after Day 1
• Pregnant and breastfeeding individuals are excluded from this clinical study

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

Double blind

Primary purpose

Treatment

Study locations

United States · 22 centers

• Retinal Consultants Of Arizona - Phoenix - North /ID# 283407 — Phoenix
• Retina Macula Institute of Arizona /ID# 282881 — Scottsdale
• The Retina Partners /ID# 274741 — Encino
• Northern California Retina Vitreous Associates /ID# 282994 — Mountain View
• California Eye Specialists Medical Group /ID# 274705 — Pasadena
• Retina Consultants San Diego /ID# 274748 — Poway
• Macula Retina Vitreous Center - Torrance /ID# 282878 — Torrance
• Southwest Retina Research Center /ID# 276094 — Durango
• … and 14 more centers

Puerto Rico · 1 center

• Emanuelli Research & Development Center /ID# 275378 — Arecibo

Identifiers

NCT: NCT07592273 · M23-415

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗