Diabetic Retinopathy
Conditions
Keywords
Diabetic Retinopathy, Severe Nonproliferative Diabetic Retinopathy, ABBV-RGX-314
Brief summary
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
DRUGSurabgene Lomparvovec
Solution Injection
DRUGSham
needleless injection without fluid
DRUGTopical Steroid
Topical Drops
DRUGArtificial Tears
Topical Drops
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2B: Percentage of Participants Achieving >= 2-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 52 | 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 | At Week 52 | 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) | Up to Approximately Week 104 | 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 | Up to Approximately Week 104 | Percentage of participants who experience intraocular inflammation. |
| Bilateral Portion: Participants Who Experience Scleral Inflammation Including Episcleritis | Up to Approximately Week 104 | Percentage of participants who experience scleral inflammation including episcleritis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2B: Percentage of Participants Who Develop a Vision-Threatening Event (VTE) due to Diabetic Retinopathy (DR) | Up to Approximately Week 52 | 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 | Up to Approximately Week 52 | Participants will be assessed for the progression to PDR or ASNV. |
| Phase 2B: Percentage of Participants Who Develop Center Involved-Diabetic Macular Edema (CI-DME) in the Study Eye | Up to Approximately Week 52 | Participants will be assessed for the development of CI-DME. |
| Phase 2B: Percentage of Participants Achieving >= 2-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 104 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Participants Who Develop Treatment-Emergent Ocular Inflammation in the Study Eye. | Up to approximately Week 14 | Percentage of participants who develop treatment-emergent ocular inflammation. |
| Phase 2B: Percentage of Participants Achieving>= 2-Step Worsening from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 52 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Percentage of Participants Achieving >= 2-Step Worsening from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 104 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Percentage of Participants With No Change from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 52 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Percentage of participants With No Change from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 104 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Percentage of Participants Achieving >= 2-Step or >= 3-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye. | At Week 52 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Percentage of Participants Achieving >= 3-Step Worsening from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 52 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Participants With Change from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 52 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Percentage of Participants With Change from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 104 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 2B: Participants Who Develop Treatment-Emergent Ocular Inflammation in the Study Eye, Comparing 2 Topical Corticosteroid Regimens for Ocular Inflammation Prophylaxis | Up to approximately Week 14 | Percentage of participants who develop treatment-emergent ocular inflammation, comparing 2 topical corticosteroid regimens for ocular inflammation prophylaxis. |
| Phase 2B: Participants Who Receive Treatments for Diabetic Retinopathy (DR) Complications in the Study Eye | Up to Approximately Week 52 | Percentage of participants who receive treatments for DR complications in the study eye. |
| Phase 3 (key secondary): Percentage of Participants who develop a Vision-Threatening Event (VTE) due to Diabetic Retinopathy (DR) | Up to Approximately Week 52 | Participants will be assessed for the development of VTEs |
| Phase 3 (key secondary): Percentage of Participants Who Experience Progression to Proliferative Diabetic Retinopathy (PDR) or Anterior Segment Neovascularization (ASNV) in the Study Eye | Up to Approximately Week 52 | Participants will be assessed for the progression to PDR or ASNV. |
| Phase 3 (key secondary): Percentage of Participants Who Develop Center Involved-Diabetic Macular Edema (CI-DME) in the Study Eye | Up to Approximately Week 52 | Participants will be assessed for the development of CI-DME. |
| Phase 3 (key secondary):Percentage of Participants Achieving >= 2-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 104 | 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 Worsening from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 104 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 3: Percentage of Participants With No change from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 52 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 3: Percentage of Participants With Change from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 104 | 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 or >= 3-Step Improvement from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye. | At Week 52 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 3: Percentage of Participants Achieving >= 3-Step Worsening from Baseline in Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye | At Week 52 | The DRSS is a scale the measures the severity of DR with a higher score indicating greater severity. |
| Phase 3: Percentage of Participants Who Receive Treatments for Diabetic Retinopathy (DR) Complications in the Study Eye | Up to approximately Week 52 | Percentage of participants who receive treatments for DR complications in the study eye. |
| Bilateral Portion: Percentage of Participants Experiencing Nonocular Adverse Events (AE)s | Up to Approximately Week 104 | 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: Percentage of Participants Experiencing Nonocular Serious Adverse Events (SAE)s | Up to Approximately Week 104 | An SAE is defined as any AE, whether or not associated with study treatment that meets any of the following criteria: death of a participant, hospitalization or prolonged hospitalization, congenital anomaly, persistent or significant disability/incapacity, and important medical event requiring medical or surgical intervention to prevent serious outcome. |
| Bilateral Portion: Percentage of Participants With Vector Shedding in Urine | Up to Approximately Week 12 | Vector shedding in urine is defined as measurement of vector Deoxyribonucleic Acid (DNA) concentrations in urine. |
| Bilateral Portion: Percentage of Participants With Vector Shedding in Tears | Up to Approximately Week 12 | Vector shedding in tears is defined as measurement of vector DNA concentrations in tears. |
| Bilateral Portion: Percentage of Participants With Vector DNA Concentrations in Serum | Up to Approximately Week 104 | Vector shedding in urine is defined as measurement of vector DNA concentrations in serum. |
| Bilateral Portion: Percentage of Participants With Change from Baseline in Diabetic Retinopathy Severity Scale (DRSS) Level | Up to Approximately Week 104 | Change from baseline in DRSS level is defined as 0-step (no change), a ≥ 1-step, a ≥ 2-step, or a ≥ 3-step change. |
| Bilateral Portion: Maintenance of Visual Acuity From Baseline | Up to Approximately Week 104 | Maintenance of visual acuity is defined as not losing 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline. |
| Bilateral portion: Change from baseline in serum anti-sura-vec Transgene product (TP) antibodies | Up to Approximately Week 104 | Change from baseline in serum anti-sura-vec antibodies |
| Bilateral Portion: Change from Baseline in Central Retinal Thickness (CRT) on Spectral Domain-Optical Coherence Tomography (SD-OCT) | Up to Approximately Week 104 | Change from baseline in CRT on SD-OCT. |
| Bilateral Portion: Change from Baseline in Aqueous Humor Surabgene Lomparvovec (Sura-vec) Transgene product (TP) Concentration | Up to Approximately Week 104 | Change from baseline in aqueous humor sura-vec TP concentration. |
| Bilateral Portion: Change from Baseline in Serum Sura-vec Transgene product (TP) concentration | Up to Approximately Week 104 | Change from baseline in serum sura-vec TP concentration. |
| Bilateral Portion: Change from Baseline in Anti- Associated Virus Serotype 8 (AAV8) Transgene product (TP) antibodies | Up to Approximately Week 104 | Change from baseline in serum anti-AAV8 TP antibodies. |
| Bilateral Portion: Percentage of Participants who develop a Vision-Threatening Event (VTE) due to Diabetic Retinopathy (DR) | Up to Approximately Week 104 | Participants will be assessed for the development of VTEs |
| Bilateral Portion: Change from Baseline in Enzyme-linked ImmunoSpot (ELISpot to capsid or transgene) | Up to Approximately Week 104 | Change from baseline in ELISpot comparing (whole blood) to capsid or transgene. |
Countries
United States
Contacts
CONTACTABBVIE CALL CENTER
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed