Safety and Tolerability of VGR-R01 in Patients With Bietti Crystalline Dystrophy

An Open-Label Safety Study of Single-dose VGR-R01 in Patients With Bietti Crystalline Dystrophy

An Open-Label, Non-Randomized, Uncontrolled, Single-dose Pilot Study of VGR-R01 in Patients with Bietti Crystalline Dystrophy.

VGR-R01 is a novel AAV vector carrying the human CYP4v2 coding sequence. This study is intended to evaluate the safety and tolerability of a single subretinal administration of VGR-R01. All subjects will undergo 365(±7) days of safety observation and will be encouraged to enroll in an extension study to evaluate the long-term safety of VGR-R01 for a total of five years.

Inclusion Criteria:

1. ≥18 years and <80 years of age;
2. Confirmed diagnosis of Bietti Crystalline Dystrophy;
3. Molecular diagnosis of CYP4v2 mutations (homozygotes or compound heterozygotes);
4. BCVA ≤ 20/200 in the study eye;
5. -8 D <diopters< +8 D, 21 mm < axial lengths ≤ 28 mm in the study eye;
6. Normal liver function and renal function；
7. Agree to use reliable barrier contraception for 1 year after administration of VGR-R01;
8. Able to provide informed consent and comply with requirements of the study. -

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. Prior medications which may interfere with the interpretation of study endpoints within six months before screening, eg. anti-VEGF drugs;
6. Have or potentially require of systemic medications that may cause eye injure;
7. Live attenuated vaccines is expected to be required during the study;
8. Participation in a clinical study with an investigational drug or medical device within three months before enrollment;
9. History of allergy or sensitivity to investigational drug, medications planned for use in the study;
10. Use of anticoagulants, or after 10 days cessation of anti-platelet agents the platelet function does not recover;
11. Use of any corticosteroids, other immunosuppressive drug(s) or antipsychotic drugs (eg. antidepressant, etc.) within 3 months prior to enrollment;
12. Have contraindications for corticosteroids or immunosuppressant;
13. Have complicating systemic diseases that would preclude the planned follow-up;
14. Abnormal coagulation function or other clinically significant abnormal laboratory results;
15. Have malignancies or history of malignancies;
16. History of immunodeficiency (acquired or congenital);
17. Females in lactation period;
18. Have a history of alcohol or illicit drug addiction;
19. Unable or unwilling to comply with the schedule of visits. -