Retinitis PigmentosaPhase 1/2ZVS203eNCT06952842
Safety and Efficacy of ZVS203e in the Treatment of Retinitis Pigmentosa Caused by RHO Gene Mutation
A Phase 1/2 study testing ZVS203e in people with Retinitis Pigmentosa, run by Chigenovo Co., Ltd at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Retinitis Pigmentosa
- What is being tested?
- ZVS203e
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 4 Aug 2025to 18 Jun 2045
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a clinical diagnosis of retinitis pigmentosa (RP) (aged 18 years or older);
- RHO (c.403C>T, p.R135W) gene site-specific mutation was confirmed by genetic testing, and no other ophthalmic genetic diseases were complicated;
- The researchers judged that the target eye had viable retinal photoreceptor cells and retinal pigment epithelial cells;
- The best corrected visual acuity of the target eye is between 2.0 LogMAR and 0.5 LogMAR (including 2.0 LogMAR and 0.5 LogMAR, which is equivalent to a number of fingers to 60 letters);
- The subject and his or her spouse agree to use effective contraception during the trial period and for at least 1 year after dosing;
- Voluntarily participate in clinical trials and sign informed consent, and can complete the whole test process according to the protocol requirements.
Who cannot join
- The researcher determined that the target eye currently has or had macular lesions such as macular hiatal hole or macular neovascularization;
- Have other eye conditions that may prevent surgery or interfere with interpretation of the study endpoint, such as glaucoma, diabetic retinopathy, eye or periocular infections, active endophthalmitis, etc.
- Within 3 months prior to enrollment, the study eye had received any intraocular surgery, such as phacoemulsification cataract extraction.
- The study eye had undergone retinal reattachment or vitrectomy.
- Participants who had participated in any drug or medical device clinical trial within 3 months before enrollment;
- Previously treatment of either eye with gene therapy or stem cell therapy for RP and other ocular diseases, including but not limited to viral vector gene therapy, RNA therapy.
- Treatment with medications that may affect the efficacy and safety evaluation of the investigational product within 3 months prior to enrollment (e.g., ranibizumab, bevacizumab, aflibercept, conbercept).
- Known allergy to the drug planned to be used in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking University Third Hospital
Beijing, Beijing Municipality, 100191
About this study
Official title: A Single-Arm, Open-Label, Phase 1/2 Clinical Trial of ZVS203e in Subjects With Retinitis Pigmentosa Associated With RHO Mutation
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.
Read the detailed description
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.
- Conditions
- Retinitis Pigmentosa
- Being tested
- ZVS203e
- Keywords
- Gene editing, ZVS203e, RHO, Retinitis pigmentosa
- Medical subject headings
- Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZVS203eDrug
Also called rAAV8
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.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | All patients enrolled in the study will receive a single subretinal injection of ZVS203e in one eye Receives: Drug: ZVS203e |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 weeks post-treatment
Secondary outcomes (5)
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.
Measured: 24 weeks post-treatment
Change from Baseline in OCT
Compare changes in retinal morphology and alterations in cell layers of the retina before and after drug administration.
Measured: 24 weeks post-treatment
Evaluate the immunogenicity of ZVS203e
Changes in SauriCas9 antibody, AAV8 antibody, and neutralizing antibody levels from baseline in the subjects.
Measured: 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.
Measured: 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).
Measured: 24 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2025
- Study start4 Aug 2025
- Primary completion18 Jun 2030 (estimated)
- Study completion18 Jun 2045 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Retinitis PigmentosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chigenovo Co., Ltd
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Hongliang Dou, M.D., Principal investigator, Peking University Third Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06952842
- Sponsor's protocol ID
- ZYB-2025-001
- Acronym
- ZVS203e
- Status last verified
- Jun 2026
- First submitted
- 22 Apr 2025
- Last updated
- 17 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34919893Liu 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.
PubMed 37272616
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm, Open-Label, Phase 1/2 Clinical Trial of ZVS203e in Subjects With Retinitis Pigmentosa Associated With RHO Mutation
- ClinicalTrials.gov ID
- NCT06952842
- Acronym / sponsor ID
- ZVS203e / ZYB-2025-001
- Conditions
- Retinitis Pigmentosa
- Keywords
- Gene editing, ZVS203e, RHO, Retinitis pigmentosa
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Chigenovo Co., LtdResearch network
- Study start
- 4 Aug 2025 (actual)
- Primary completion
- 18 Jun 2030 (estimated)
- Study completion
- 18 Jun 2045 (estimated)
- First posted
- 1 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: ZVS203eAll patients enrolled in the study will receive a single subretinal injection of ZVS203e in one eye |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with a clinical diagnosis of retinitis pigmentosa (RP) (aged 18 years or older);
- RHO (c.403C>T, p.R135W) gene site-specific mutation was confirmed by genetic testing, and no other ophthalmic genetic diseases were complicated;
- The researchers judged that the target eye had viable retinal photoreceptor cells and retinal pigment epithelial cells;
- The best corrected visual acuity of the target eye is between 2.0 LogMAR and 0.5 LogMAR (including 2.0 LogMAR and 0.5 LogMAR, which is equivalent to a number of fingers to 60 letters);
- The subject and his or her spouse agree to use effective contraception during the trial period and for at least 1 year after dosing;
Key exclusion criteria (8 listed)
- The researcher determined that the target eye currently has or had macular lesions such as macular hiatal hole or macular neovascularization;
- Have other eye conditions that may prevent surgery or interfere with interpretation of the study endpoint, such as glaucoma, diabetic retinopathy, eye or periocular infections, active endophthalmitis, etc.
- Within 3 months prior to enrollment, the study eye had received any intraocular surgery, such as phacoemulsification cataract extraction.
- The study eye had undergone retinal reattachment or vitrectomy.
- Participants who had participated in any drug or medical device clinical trial within 3 months before enrollment;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZVS203eAlso: rAAV8ZVS203e 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. | Drug | Single arm |
Primary outcome
Evaluate the safety and tolerability of subretinal injection of ZVS203e solution
Time frame: 24 weeks post-treatment
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.
Change from baseline in best-corrected visual acuity (BCVA)
Time frame: 24 weeks post-treatment
Change in best-corrected visual acuity (BCVA) of the treated eye at 24 weeks compared to baseline.
5 secondary outcomes
Change from Baseline in Visual function metrics
Time frame: 24 weeks post-treatment
Change from Baseline in OCT
Time frame: 24 weeks post-treatment
Evaluate the immunogenicity of ZVS203e
Time frame: 24 weeks post-treatment
Evaluate the pharmacokinetic characteristics of ZVS203e
Time frame: 24 weeks post-treatment
Change from Baseline in multi-luminance mobility test (MLMT)
Time frame: 24 weeks post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
- Background: PubMed 34919893Liu 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.
- Background: PubMed 37272616Liu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hongliang Dou, M.D. principal investigator
Peking University Third Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ZVS203e in people with Retinitis Pigmentosa, run by Chigenovo Co., Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jinlu Zhang, MD (15810570898, zhangjinlu@chinagene.cc), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and tolerability of subretinal injection of ZVS203e solution (time frame: 24 weeks post-treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06952842, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.