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Primary Objectives: To evaluate the safety of rAAV2/8-hCYP4V2 gene replacement therapy drug administered as a single subretinal injection in patients with Bietti's Crystalline Dystrophy (BCD).
Secondary Objectives: To preliminarily explore the clinical effectiveness of rAAV2/8-hCYP4V2 gene replacement therapy drugs.
This is a single-arm, open-label, and single-center study of ZVS101e in patients with BCD. A total of 12 participants will be enrolled. A retinal surgeon will administer the vector by subretinal injection. Safety, efficacy and vector shedding characteristics of ZVS101e are then measured over 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm | Experimental | All patients enrolled in the study will receive a single subretinal injection of ZVS101e in one eye |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rAAV2/8-hCYP4V2 | Drug | rAAV2/8-hCYP4V2 is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events | Incidence of adverse events, vital signs, physical examination, ophthalmic 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. | 24 months |
| Incidence of serious adverse events | A serious adverse event (SAE) is any untoward medical occurrence at any dose that leading to the following: Results in death; Life-threatening, refers to an event in which the patient is at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe; Significant or permanent disability/incapacity, where disability refers to a serious disruption and damage of a person's ability to perform normal life functions; Requires inpatient hospitalization or prolongation of existing hospitalization; Congenital anomaly or birth defect; Other medically important events | 24 months |
| Clinically important changes from baseline after ZVS101e treatment | Clinically important changes including abnormal physical examinations, vital signs, ECG, laboratory findings (chemistry, hematology, urinalysis) and ophthalmologic findings (BCVA, slit lamp examination, ophthalmoscopy, IOP, funds photography, FAF, OCT, OCTA). | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Mean change from baseline in BCVA after ZVS101e treatment | BCVA of both eyes will be assessed using the early treatment of diabetic retinopathy study (ETDRS) chart | 24 months |
| Change from Baseline in visual field |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| wenbin Wei, Doctor | Contact | 13701255115 | tr_weiwenbin@163.com | |
| xiuli Zhao, Doctor | Contact | 18811612056 | xiulizhao@medmail.com.cn |
| Name | Affiliation | Role |
|---|---|---|
| wenbin Wei, Doctor | Vice President of Beijing Tongren Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Tongren Hospital | Recruiting | Beijing | Beijing Municipality | 100730 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35925866 | Background | Jia R, Meng X, Chen S, Zhang F, Du J, Liu X, Yang L. AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice. Hum Mol Genet. 2023 Jan 1;32(1):122-138. doi: 10.1093/hmg/ddac181. |
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| ID | Term |
|---|---|
| C535440 | Bietti Crystalline Dystrophy |
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Visual field will be assessed by Humphrey perimetry, changes in VFI, MD, PSD will be analyzed.
| 24 months |
| Change from Baseline in contrast sensitivity | Change from baseline in contrast sensitivity will be measured using the CSV-1000E instrument. | 24 months |
| Change from Baseline in multi-luminance mobility test (MLMT) | MLMT was assessed at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night). The score range is between -1 (the worst) and 6 (the best). | 24 months |
| Change from Baseline in OCTA | The OCTA examines the retinal and choroidal vessels. The retinal and choroidal vessel perfusion area, vessel volume, and vessel index will be analyzed. | 24 months |
| Change from Baseline in microperimetry | Microperimetry will be measured using MP-3,changes in retinal light sensitivity will be analyzed. | 24 months |
| Change from Baseline in mfERG | The measurement will be performed based on the standards of international society for clinical electrophysiology of vision (ISCEV).The change of retinal function in the macula will be analyzed. | 24 months |
| Change from Baseline in retinal thickness | Retinal thickness will be assessed for both eyes using OCT. | 24 months |
| Change from Baseline in NEI VFQ-25 total score | National eye institute 25-item visual function questionnaire (NEI VFQ-25) consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. | 24 months |
| Change from Baseline in fundus autofluorescence (FAF) | FAF is a noninvasive test to explore the health and metabolic status of retinal pigment epithelial cell/photoreceptor complex. | 24 months |