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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
rAAV2/8-hCYP4V2 is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene
Beijing Tongren Hospital
Beijing, Beijing Municipality, China
RECRUITINGIncidence 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.
Time frame: 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
Time frame: 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).
Time frame: 24 months
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
Time frame: 24 months
Change from Baseline in visual field
Visual field will be assessed by Humphrey perimetry, changes in VFI, MD, PSD will be analyzed.
Time frame: 24 months
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Change from Baseline in contrast sensitivity
Change from baseline in contrast sensitivity will be measured using the CSV-1000E instrument.
Time frame: 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).
Time frame: 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.
Time frame: 24 months
Change from Baseline in microperimetry
Microperimetry will be measured using MP-3,changes in retinal light sensitivity will be analyzed.
Time frame: 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.
Time frame: 24 months
Change from Baseline in retinal thickness
Retinal thickness will be assessed for both eyes using OCT.
Time frame: 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.
Time frame: 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.
Time frame: 24 months