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

Phase 1

Not yet recruiting

• Conditions: Bietti Crystalline Dystrophy
• Interventions: Genetic: VGR-R01

• Registration Number: NCT05694598
• Lead Sponsor: Shanghai Vitalgen BioPharma Co., Ltd.

Brief Summary

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

Detailed Description

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.

Study Timeline

• Status Verified: 2023-01
• Study First Submitted: 2023-01-11
• Study First Submitted QC: 2023-01-20
• Last Update Submitted: 2023-01-20
• Study First Posted: 2023-01-23
• Last Update Posted: 2023-01-23
• Study Start: 2023-03-01
• Primary Completion: 2025-03-01
• Study Completion: 2025-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

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. 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/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
VGR-R01	VGR-R01	Single-dose Subretinal Administration of VGR-R01

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events	Baseline up to Week 52	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.
Number of Participants with Clinically Significant Change from Baseline in Vital Signs	Baseline up to Week 52	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.
Number of Participants with Clinically Laboratory Abnormalities	Baseline up to Week 52	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.
Number of Participants with Clinically Significant Change from Baseline in Ophthalmic Examination Findings	Baseline up to Week 52	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.
Incidence of serious adverse events	Baseline up to Week 52	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.

Secondary Outcome Measures

Name	Time	Method
Changes from baseline in Mobility testing scores	Week 52	The mobility score range is between -1 (the worst functional vision) and 6 (the best).
Changes from baseline of Mean Deviation (dB) in Visual Field (Humphery perimetry) indexes	Week 52	Normal values are typically within 0dB and -2dB.
Changes from baseline of Visual Field Index (%) in Visual Field (Humphery perimetry) indexes	Week 52	The VFI can range from 100% (normal visual field) to 0% (perimetrically blind field).
Changes from baseline of Pattern Standard Deviation (dB) in Visual Field (Humphery perimetry) indexes	Week 52	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).
Best-Corrected Visual Acuity (BCVA)	Week 52	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.

Trial Locations

Locations (1)

Shanghai Vitalgen Biopharma Co.,Ltd.; 🇨🇳 Shanghai, Shanghai, China