The purpose of the study is to evaluate the safety and tolerability of an adeno-associated virus vector expressing CYP4V2 in patients with Bietti's crystalline dystrophy (BCD).
This is a single-arm, open-label, and single-center study of ZVS101e in patients with BCD. A total of 6 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
6
ZVS101e is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene.
Peking University Third Hospital
Beijing, Beijing Municipality, China
RECRUITINGIncidence of ocular and systemic adverse events (AEs) after ZVS101e treatment.
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: Baseline up to Week 52
Incidence of ocular and systemic serious adverse events (SAEs) after ZVS101e treatment.
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: Baseline up to Week 52
Type and severity of ocular and systemic AEs and SAEs after ZVS101e treatment.
Safety as the primary endpoint will be assessed by best-corrected visual acuity (BCVA), slit-lamp examination, ophthalmoscopy, fundus photography, intraocular pressure (IOP), optical coherence tomography (OCT), laboratory tests, vital signs, physical examinations, electrocardiogram (ECG), immunopathology and biodistribution of ZVS101e.
Time frame: Baseline up to Week 52
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: Baseline up to Week 52
Change from Baseline in visual field
Visual field will be assessed by Humphrey perimetry.
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Time frame: Baseline up to Week 52
Change from Baseline in contrast sensitivity
Change from baseline in contrast sensitivity will be measured using the CSV-1000E instrument.
Time frame: Baseline up to Week 52
Change from Baseline in color vision
Subjects' color vision was classified and graded by having them identify the pictures within Color Vision Examination Plates.
Time frame: Baseline up to Week 52
Change from Baseline in retinal thickness
Retinal thickness will be assessed for both eyes using OCT.
Time frame: Baseline up to Week 52
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: Baseline up to Week 52
Change from Baseline in multi-luminance mobility test (MLMT)
MLMT was assessed using both eyes at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night).
Time frame: Baseline up to Week 52
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: Baseline up to Week 52
Change from Baseline in mfERG
The measurement will be performed based on the standards of international society for clinical electrophysiology of vision (ISCEV).
Time frame: Baseline up to Week 52
Incidence of ocular and systemic AEs after ZVS101e treatment.
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: Week 53 to Week 104
Incidence of ocular and systemic SAEs after ZVS101e treatment.
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: Week 53 to Week 104
Type and severity of ocular and systemic AEs and SAEs after ZVS101e treatment.
Safety will be assessed by best-corrected visual acuity (BCVA), slit-lamp examination, ophthalmoscopy, fundus photography, intraocular pressure (IOP), optical coherence tomography (OCT), laboratory tests, vital signs, physical examinations, electrocardiogram (ECG), immunopathology and biodistribution of ZVS101e.
Time frame: Week 53 to Week 104