Bietti Crystalline Dystrophy, Inherited Retinal Diseases
Conditions
Brief summary
This is a phase 3 study to evaluate the efficacy and safety of VGR-R01 in subjects with Bietti Crystalline Dystrophy. This is a multicenter, randomized controlled study which will enroll 45 subjects.
Detailed description
VGR-R01 is a novel AAV vector carrying the human CYP4v2 coding sequence. This study is intended to assess the efficacy of VGR-R01 in subjects with Bietti crystalline dystrophy (BCD) based on the change from baseline in best corrected visual acuity (BCVA) of the study eyes. 30 subjects will be enrolled in the intervention group and will receive monocular administration of VGR-R01, and 15 subjects in the control group will not receive any intervention. After completion of the trial, the untreated eyes will receive administration of VGR-R01 in subsequent clinical trial.
Interventions
DRUGVGR-R01
Subretinal injection of VGR-R01 (0.1 mL)
Sponsors
Shanghai Vitalgen BioPharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Able to provide informed consent and comply with requirements of the study; 2. ≥18 years and \<70 years of age; 3. Confirmed diagnosis of Bietti Crystalline Dystrophy and molecular diagnosis of CYP4V2 mutations (homozygotes or compound heterozygotes); 4. Hand Motion ≤ BCVA ≤ 60 ETDRS letters in the study eye; Key
Exclusion criteria
1. Have insufficient viable retinal photoreceptor cells based on investigator's decision; 2. Have current ocular or periocular infections, or endophthalmitis; 3. Have any significant ocular disease/disorder other than BCD, including age-related macular degeneration, diabetic retinopathy, optic neuropathy, significant lens opacity, glaucoma, uveitis, retinal detachment, etc; 4. Have intraocular surgery history except cataract surgery in the study eye; 5. Have or potentially require of systemic medications that may cause eye injure; 6. Have contraindications for corticosteroids or immunosuppressant; 7. Unwilling or unable to have the planned follow-up; 8. Abnormal coagulation function or other clinically significant abnormal laboratory results; 9. Have malignancies or history of malignancies; 10. History of immunodeficiency (acquired or congenital); Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with change in BCVA in the study eyes of BCD subjects as assessed by ETDRS | Baseline up to Week 52 | Change in the BCVA assessment from screening in the study eye of BCD subjects will be compared to controls |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in BCVA | Baseline up to Week 52 | BCVA will be assessed with the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. Testing Protocol will be followed (confidential). Change in the BCVA assessment from baseline in treated eyes of intervention group will be compared to controls. |
| Change from baseline in multi-luminance mobility test (MLMT) score of the study eye | Baseline up to Week 52 | Subjects will navigate a standardized mobility maze under set conditions as specified times during the study. The mobility testing will follow a standardized administration and data acquisition protocol and may only be administered by site staff certified in the methodology. |
| Changes from baseline in Microperimetry indexes | Baseline up to Week 52 | Number of subjects with change in fixation stability or light sensitivity in treated eyes of intervention group will be compared to controls |
| Counts, frequencies and percentages of AE, SAE and other safety evaluation | Baseline up to Week 52 | Ocular/non-ocular adverse events are collected. The ophthalmic examination will include BCVA, IOP, slitlamp examination, angiography and SD-OCT, etc. If any potential changes accompanied by clinical symptoms, or results in a change of medical intervention, the findings will be considered as clinically significant based on investigator's decision |
| Number of subjects with the presence of immunogenicity | Baseline up to Week 52 | Assessed as presence of systemic cell-mediated or humoral responses to capsid or transgene product |
| Change from baseline in optical coherence tomography (OCT) | Baseline up to Week 52 | Change from baseline in central retinal thickness (CRT) as imaged by OCT |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in visual field index | Baseline up to Week 52 | Assessed by Humphery static visual field testing. |
| Change from baseline in PRO measures | Baseline up to Week 52 | As assessed by the NEI-VFQ-25 questionnaire |
Countries
China
Outcome results
None listed