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This trial employs a single-arm, open-label seamless Phase I/II design, consisting of two stages: Phase I dose exploration and Phase II dose expansion.The primary objective of this trial is to evaluate the safety, tolerability, and efficacy of subretinal injection of ZVS203e solution.
ZVS203e injection is administered via a single subretinal injection of rAAV8 vector carrying CRISPR/Cas9 gene-editing tools to silence mutated genes, allowing retinal cells to express only normal functional proteins, thereby treating RHO-adRP.
This trial employs a single-arm, open-label seamless Phase I/II design, consisting of two stages: Phase I dose escalation and Phase II dose expansion, with an anticipated total enrollment of 9 to 18 participants.
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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 ZVS203e in one eye |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZVS203e | Drug | ZVS203e injection is a clear, transparent liquid containing a recombinant adeno-associated virus serotype 8 (rAAV8) vector that expresses humanized SauriCas9 protein and single guide RNA (sgRNA) targeting specific mutations in the RHO gene. |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the safety and tolerability of subretinal injection of ZVS203e solution | Types, severity, and incidence of adverse events (AE) and serious adverse events (SAE) in the eyes and throughout the body within 24 weeks post-treatment, including dose-limiting toxicities (DLT) during the dose escalation phase. | 24 weeks post-treatment |
| Change from baseline in best-corrected visual acuity (BCVA) | Change in best-corrected visual acuity (BCVA) of the treated eye at 24 weeks compared to baseline. | 24 weeks post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in Visual function metrics | Treatment outcomes for visual function metrics include changes from baseline in LLVA, dynamic visual field, microperimetry, FST, contrast sensitivity, color vision, and mfERG; as well as changes from baseline in the NEI-VFQ-25 score reported by the participants. | 24 weeks post-treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jinlu Zhang, MD | Contact | 15810570898 | zhangjinlu@chinagene.cc |
| Name | Affiliation | Role |
|---|---|---|
| Hongliang Dou, M.D. | Peking University Third Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital | Recruiting | Beijing | Beijing Municipality | 100191 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34919893 | Background | Liu X, Jia R, Meng X, Li Y, Yang L. Retinal degeneration in humanized mice expressing mutant rhodopsin under the control of the endogenous murine promoter. Exp Eye Res. 2022 Feb;215:108893. doi: 10.1016/j.exer.2021.108893. Epub 2021 Dec 14. | |
| 37272616 | Background | Liu X, Qiao J, Jia R, Zhang F, Meng X, Li Y, Yang L. Allele-specific gene-editing approach for vision loss restoration in RHO-associated retinitis pigmentosa. Elife. 2023 Jun 5;12:e84065. doi: 10.7554/eLife.84065. |
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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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|
| Change from Baseline in OCT |
Compare changes in retinal morphology and alterations in cell layers of the retina before and after drug administration. |
| 24 weeks post-treatment |
| Evaluate the immunogenicity of ZVS203e | Changes in SauriCas9 antibody, AAV8 antibody, and neutralizing antibody levels from baseline in the subjects. | 24 weeks post-treatment |
| Evaluate the pharmacokinetic characteristics of ZVS203e | Changes in AAV8 vector DNA and mRNA levels in the blood and tears of participants compared to baseline. | 24 weeks post-treatment |
| 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). | 24 weeks post-treatment |
| D012164 |
| Retinal Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |