Bietti Crystalline Dystrophy
Conditions
Keywords
VGR-R01, CYP4V2, gene therapy
Brief summary
This is a multi-centre, single- arm, non-randomized, open-label phase 1/2 clinical trial which enables dosing of the fellow eyes of patients who received VGR-R01 administration in previous studies.
Detailed description
VGR-R01 is a novel Adeno-associated virus (AAV) vector carrying the human Cytochrome P450 Family 4 Subfamily V Member 2 (CYP4V2) coding sequence. This study will evaluate the safety and efficacy of VGR-R01 administered in the contralateral eye (the second treated eye) of subjects enrolled in the VGR-R01-001 and VGR-R01-101 studies, along with assessments of immunogenicity and vector shedding. Additionally, the long-term safety and efficacy of VGR-R01 treatment will be continuously assessed for up to 5 years after the last dose.
Interventions
BIOLOGICALVGR-R01
CYP4v2-coding gene delivered by AAV vector
Sponsors
Shanghai Vitalgen BioPharma Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants received VGR-R01 administration in the VGR-R01-001 or VGR-R01-101 studies. 2. Able to provide informed consent and comply with requirements of the study; 3. Hand Motion ≤ BCVA ≤ 75 ETDRS letters in the second treated 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. Abnormal coagulation function or other clinically significant abnormal laboratory results; 8. Have malignancies or history of malignancies; 9. History of immunodeficiency (acquired or congenital); Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events and serious adverse events | Up to Year 5 | Ocular/non-ocular adverse events are collected. The ophthalmic examination will include Best Corrected Visual Acuity (BCVA), Intraocular Pressure (IOP), slit lamp examination, angiography and Optical Coherence Tomography (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 participants with clinically significant change from baseline in vital signs, clinically laboratory abnormalities and ophthalmic examination findings | Up to Year 5 | Vital signs (temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure) will be obtained with participant in the seated position, after having sat calmly for at least 10 minutes. Laboratory Tests will include hematology, coagulation, blood chemistry, urinalysis, serology, and pregnancy test, etc. Ophthalmic Examination will include BCVA, IOP, slit lamp examination, angiography and OCT, etc. Clinical significance of the above signs will be determined at the investigator's discretion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in BCVA | Year 5 | BCVA will be assessed with the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart.. |
| Change from baseline in multi-luminance mobility test (MLMT) score | Year 5 | Subjects will navigate a standardized mobility maze under set conditions as specified times during the study. All light-levels used for testing will be rounded to one of the following specified light levels: 0.1, 1, 4, 10, 50, 125, 250, or 400 lux. The corresponding scores for the above light levels range from 7 to 0, in descending order. -1 point means failing to pass the test at the 400 lux level; the lower the score, the worse the functional vision of the participant. |
| Change from baseline in optical coherence tomography (OCT) | Year 5 | Change from baseline in central retinal thickness (CRT) as imaged by OCT. |
| Number of subjects with the presence of immunogenicity | Year 5 | Assessed as presence of systemic cell-mediated or humoral responses to capsid or transgene product. |
| Number of subjects with the presence of vector shedding | Year 5 | Assessed as the presence of vector in peripheral blood or collected tear. |
| Fixation stability | Year 5 | Number of treated eyes with changes from baseline in fixation stability with MP-3 Microperimetry. Fixation stability is rated into three levels: stable fixation, relatively unstable fixation, and unstable fixation, with fixed standard reporting on the device settings. |
| Light sensitivity | Year 5 | Changes from baseline in light sensitivity with MP-3 Microperimetry. The MP-3 has a stimulus intensity range of 0 to 34 decibels (dB). |
Countries
China
Contacts
CONTACTYan Jiang
PRINCIPAL_INVESTIGATORWenbin Wei
Beijing Tongren Hospital
Outcome results
None listed