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The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of ZVS203e administered via subretinal injection in participants with RP caused by RHO site-specific gene mutation (RHO-RP).
This is a single-arm, open-label, single ascending dose study of ZVS203e in participants with RHO-RP. Up to 9 participants will be enrolled in this study. Safety, efficacy and vector shedding characteristics of ZVS203e are then measured.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose escalation | Experimental | Three cohorts of 3 patients each. All the patients enrolled in the study will receive a single subretinal injection in one eye. Cohort 1: Subretinal administration of a single low dose ZVS203e at Day 0. Cohort 2: Subretinal administration of a single medium dose ZVS203e at Day 0. Cohort 3: Subretinal administration of a single high dose ZVS203e at Day 0. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZVS203e | Drug | ZVS203e is a rAAV-mediated gene editing drug that silences RHO mutant protein expression by CRISPR/Cas9 editing system. |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events (AEs) | 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 (SAEs) | 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. | Baseline up to Week 52 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean change from baseline in BCVA after ZVS203e treatment | BCVA of both eyes will be assessed using the early treatment of diabetic retinopathy study (ETDRS) chart. | Baseline up to Week 52 |
| Change from Baseline in visual field |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Liping Yang, MD | Contact | 010-82266595 | alexlipingyang@bjmu.edu.cn | |
| Jinlu Zhang, MD | Contact | 15810570898 | zhangjinlu@bjmu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Liping Yang, MD | Peking University Third Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital | Recruiting | Beijing | Beijing Municipality | 100191 | China |
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| ID | Term |
|---|---|
| D012174 | Retinitis Pigmentosa |
| ID | Term |
|---|---|
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D058499 | Retinal Dystrophies |
| D012162 | Retinal Degeneration |
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Visual field will be assessed by Humphrey perimetry, changes in VFI, MD, PSD will be analyzed.
| 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. | Baseline up to Week 52 |
| 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). | Baseline up to Week 52 |
| Change from Baseline in retinal thickness | Retinal thickness will be assessed for both eyes using OCT. | 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. | Baseline up to Week 52 |
| Change from Baseline in color vision | Subjects' color vision was classified and graded by Farnsworth Munsell 100 hue. | 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). | 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. | Baseline up to Week 52 |
| D012164 |
| Retinal Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |