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

Study Overview
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Brief Summary
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A Multicenter, Open-Label, Non-Randomized, Uncontrolled Study of VGR-R01 in Patients with Bietti Crystalline Dystrophy.

Detailed Description
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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 at least 52 weeks 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.

Official Title
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A Phase 1 Study to Assess the Safety and Tolerability of VGR-R01 in Patients With Bietti Crystalline Dystrophy

Conditions
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Bietti Crystalline Dystrophy

Intervention / Treatment
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* Genetic: VGR-R01


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Able to provide informed consent and comply with requirements of the study; ≥18 years and <70 years of age; Confirmed diagnosis of Bietti Crystalline Dystrophy and molecular diagnosis of CYP4V2 mutations (homozygotes or compound heterozygotes); BCVA ≤ 60 ETDRS letters in the study eye. Key Exclusion Criteria: Have insufficient viable retinal photoreceptor cells based on investigator's decision; Have current ocular or periocular infections, or endophthalmitis; 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; Have intraocular surgery history except cataract surgery in the study eye; Have or potentially require of systemic medications that may cause eye injure; Have contraindications for corticosteroids or immunosuppressant; Unwilling or unable to have the planned follow-up; Abnormal coagulation function or other clinically significant abnormal laboratory results; Have malignancies or history of malignancies; History of immunodeficiency (acquired or congenital); Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VGR-R01<br>Single-dose Subretinal Administration of VGR-R01 | Genetic: VGR-R01<br>* CYP4v2-coding gene delivered by AAV vector<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment. | Baseline up to Week 52 | 
| Incidence of serious adverse events | A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening; require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect. | Baseline up to Week 52 | 
| Number of Participants with Clinically Significant Change from Baseline in Vital Signs | 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 5 minutes. Clinical significance of vital signs will be determined at the investigator's discretion. | Baseline up to Week 52 | 
| Number of Participants with Clinically Laboratory Abnormalities | Laboratory Tests will include hematology, coagulation, blood chemistry, urinalysis, serology, and pregnancy test, 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. | Baseline up to Week 52 | 
| Number of Participants with Clinically Significant Change from Baseline in Ophthalmic Examination Findings | 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. | Baseline up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best-Corrected Visual Acuity (BCVA) | BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. | Week 52 | 
| Changes from baseline of Visual Field Index (%) in Visual Field (Humphery perimetry) indexes | The VFI can range from 100% (normal visual field) to 0% (perimetrically blind field). | Week 52 | 
| Changes from baseline of Mean Deviation (dB) in Visual Field (Humphery perimetry) indexes | Normal values are typically within 0dB and -2dB. | Week 52 | 
| Changes from baseline of Pattern Standard Deviation (dB) in Visual Field (Humphery perimetry) indexes | A typical normal dB reading is around 30. The numeric dB graph should be studied next. The dBs tested by the Humphrey analyzer range between 0 and 50 dB (0 is the brightest and 50 is the dimmest). | Week 52 | 
| Changes from baseline in Mobility testing scores | The mobility score range is between -1 (the worst functional vision) and 6 (the best). | Week 52 |