Retinitis PigmentosaEarly Phase 1NCT05805007
Safety and Tolerability Study of Gene Editing Drug ZVS203e in Participants With Retinitis Pigmentosa
A Early Phase 1 study testing ZVS203e in people with Retinitis Pigmentosa, run by Peking University Third Hospital at 1 site in China.
Trial summary
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. 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
- 9 participants
- Where
- 1 siteChina
- Study dates
- 12 Sep 2023to Dec 2028
- Phase
- Early Phase 1
- 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
- 1. Patients with clinical diagnosis of Retinitis Pigmentosa (RP) (age ≥ 18 years) ;
- 2. Genetic test confirmed to carry a fix mutation of RHO and carry no pathogenic mutations of other ophthalmic genetic diseases;
- 3. Meet the following target eye selection criteria： Best corrected visual acuity between 2.3 LogMAR and 0.5 LogMAR (including 2.3 LogMAR and 0.5 LogMAR, equivalent to Snellen visual acuity of hand move to 20/63) ;
- 4. Agree to take effective contraceptive measures from the beginning of the study to 1 year after the administration;
- 5.Willingness to adhere to protocol as evidenced by written informed consent;
- Definition of the study eye: The study eye is defined as the eye with worse visual acuity between the two eyes of each prospective subject. For all subjects, only one eye shall be designated as the "study eye" (i.e., the eye receiving treatment). If both eyes of a patient meet the eligibility criteria and have equal visual acuity, the investigator shall determine the study eye based on clinical judgment.
Who cannot join
- 1. Existing or pre-existing of macular lesions such as retinoschisis or macular membrane, or other eye conditions interfering with the surgery or the interpretation of the clinical endpoint, in the investigators' opinion;
- 2. The study eye has been treated with other drugs within 3 months that could affect the evaluation of the investigational drug;
- 3. The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;
- 4. The presence of an ocular/visual disease, disorder or lesion known to cause, or to be associated with, vision loss, or whose associated treatment or therapy is known to cause, or to be associated with, vision loss；
- 5. Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;
- 6. Known allergy to the drug planned for use in the study；
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- 7.Those with the following laboratory abnormalities which are clinically significant: Liver function: chronic liver disease, ALT increased >2 times the upper limit of normal; With uncontrolled hypertension, mean systolic blood pressure ≥ 160 mmHg or mean diastolic blood pressure ≥ 100 mmHg; With uncontrolled diabetes, HbA1c>10%; Patients with abnormal coagulation function (prothrombin time ≥ upper limit of normal (3 seconds' longer), activated partial thromboplastin time ≥ upper limit of normal (10 seconds' longer)); Serum virology test: Active hepatitis B, hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab) or syphilis antibody positive;
- 8. Having any past or present medical history that may affect the safety of the trial or the in vivo process of the drug, especially the medical history of cardiovascular, hepatic, renal, endocrine, gastrointestinal, pulmonary, neurological, hematological, oncologic, immunological or metabolic disorders and others that are thought clinically significant by the investigator；
- 9. Participation in any medicine or medical device clinical trials within 3 months prior to enrollment;
- 10. Neutralizing antibodies to rAAV> 1:1000 by immunologic test;
- 11. For females in pregnancy or lactation period;
- 12. Any other conditions which leads the investigator to determine the participant is unsuitable for this 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
Jinlu Zhang, MD, 15810570898, zhangjinlu@bjmu.edu.cn
Bingqian Cong, Bachelor, 18500191916, congbingqian@chinagene.cc
About this study
Official title: A Single-arm, Open-label Exploratory Clinical Study to Assess the Preliminary Safety of the Gene Editing Drug ZVS203e for the Management of Retinitis Pigmentosa Caused by Mutations in the RHO Gene
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.
Read the detailed description
ZVS203e injection is an experimental rAAV8-mediated gene therapy drug intended for the treatment of retinitis pigmentosa caused by specific mutations in the RHO gene. Administered via subretinal injection, it directly delivers gene-editing tools to photoreceptor cells and retinal pigment epithelial (RPE) cells. Up to 9 participants will be enrolled in this study. Safety, efficacy and vector shedding characteristics of ZVS203e are then measured. The study duration for each subject includes the screening period, treatment period, core visit period, 1-year safety follow-up, and end of study.
- Conditions
- Retinitis Pigmentosa
- Being tested
- ZVS203e
- Keywords
- gene editing, retinitis pigmentosa, RHO, rAAV
- 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
ZVS203e is a rAAV-mediated gene editing drug that silences RHO mutant protein expression by CRISPR/Cas9 editing system.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: ZVS203e |
What is being measured
The primary outcome is the main question the study is designed to answer.
AEs and SAEs
Type, severity, and incidence of ocular and systemic adverse events (AEs) and serious adverse events (SAEs) in the study eye after ZVS203e administration.
Measured: Baseline up to Week 52
Immunogenicity Testing
Immunogenicity following subretinal administration of ZVS203e injection, including T-cell immune responses against SauriCas9 and AAV8, and titers of anti-SauriCas9 binding antibodies, anti-AAV8 binding antibodies, and anti-AAV8 neutralizing antibodies.
Measured: Baseline up to Week 52
Vector Shedding
Vector DNA shedding in blood and tears following subretinal administration of ZVS203e injection.
Measured: Baseline up to Week 52
Secondary outcomes (7)
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.
Measured: Baseline up to Week 52
Change from Baseline in Visual Field
Visual field will be assessed by Humphrey perimetry, changes in VFI, MD, PSD will be analyzed.
Measured: 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.
Measured: Baseline up to Week 52
Change from Baseline in Color Vision
Subjects' color vision was classified and graded by Farnsworth Munsell 100 hue.
Measured: 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).
Measured: Baseline up to Week 52
Change from Baseline in Retinal Thickness
Retinal thickness will be assessed for both eyes using OCT.
Measured: 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.
Measured: Baseline up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2023
- Study start12 Sep 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinitis PigmentosaStudies of the same condition, open and under way.
- More trials run by Peking University Third HospitalThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-dose, dose-escalation safety study with three pre-specified dose levels (low, medium, and high). A total of 9 subjects are planned to be enrolled.
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Third Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Liping Yang, MD, Principal investigator, Peking University Third Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05805007
- Sponsor's protocol ID
- ZYB-2022-001
- Status last verified
- Sep 2026
- First submitted
- 14 Mar 2023
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open-label Exploratory Clinical Study to Assess the Preliminary Safety of the Gene Editing Drug ZVS203e for the Management of Retinitis Pigmentosa Caused by Mutations in the RHO Gene
- ClinicalTrials.gov ID
- NCT05805007
- Acronym / sponsor ID
- ZYB-2022-001
- Conditions
- Retinitis Pigmentosa
- Keywords
- gene editing, retinitis pigmentosa, RHO, rAAV
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Peking University Third HospitalUniversity, hospital or other
- Study start
- 12 Sep 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 7 Apr 2023 (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.
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.
Detailed description
ZVS203e injection is an experimental rAAV8-mediated gene therapy drug intended for the treatment of retinitis pigmentosa caused by specific mutations in the RHO gene. Administered via subretinal injection, it directly delivers gene-editing tools to photoreceptor cells and retinal pigment epithelial (RPE) cells. Up to 9 participants will be enrolled in this study. Safety, efficacy and vector shedding characteristics of ZVS203e are then measured. The study duration for each subject includes the screening period, treatment period, core visit period, 1-year safety follow-up, and end of study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-dose, dose-escalation safety study with three pre-specified dose levels (low, medium, and high). A total of 9 subjects are planned to be enrolled.
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: ZVS203eThree 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 1. Patients with clinical diagnosis of Retinitis Pigmentosa (RP) (age ≥ 18 years) ;
- 2. Genetic test confirmed to carry a fix mutation of RHO and carry no pathogenic mutations of other ophthalmic genetic diseases;
- 3. Meet the following target eye selection criteria： Best corrected visual acuity between 2.3 LogMAR and 0.5 LogMAR (including 2.3 LogMAR and 0.5 LogMAR, equivalent to Snellen visual acuity of hand move to 20/63) ;
- 4. Agree to take effective contraceptive measures from the beginning of the study to 1 year after the administration;
- 5.Willingness to adhere to protocol as evidenced by written informed consent;
Key exclusion criteria (12 listed)
- 1. Existing or pre-existing of macular lesions such as retinoschisis or macular membrane, or other eye conditions interfering with the surgery or the interpretation of the clinical endpoint, in the investigators' opinion;
- 2. The study eye has been treated with other drugs within 3 months that could affect the evaluation of the investigational drug;
- 3. The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;
- 4. The presence of an ocular/visual disease, disorder or lesion known to cause, or to be associated with, vision loss, or whose associated treatment or therapy is known to cause, or to be associated with, vision loss；
- 5. Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;
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 |
|---|---|---|
| ZVS203eZVS203e is a rAAV-mediated gene editing drug that silences RHO mutant protein expression by CRISPR/Cas9 editing system. | Drug | Dose escalation |
Primary outcome
AEs and SAEs
Time frame: Baseline up to Week 52
Type, severity, and incidence of ocular and systemic adverse events (AEs) and serious adverse events (SAEs) in the study eye after ZVS203e administration.
Immunogenicity Testing
Time frame: Baseline up to Week 52
Immunogenicity following subretinal administration of ZVS203e injection, including T-cell immune responses against SauriCas9 and AAV8, and titers of anti-SauriCas9 binding antibodies, anti-AAV8 binding antibodies, and anti-AAV8 neutralizing antibodies.
Vector Shedding
Time frame: Baseline up to Week 52
Vector DNA shedding in blood and tears following subretinal administration of ZVS203e injection.
7 secondary outcomes
Change from Baseline in BCVA after ZVS203e Treatment
Time frame: Baseline up to Week 52
Change from Baseline in Visual Field
Time frame: Baseline up to Week 52
Change from Baseline in Contrast Sensitivity
Time frame: Baseline up to Week 52
Change from Baseline in Color Vision
Time frame: Baseline up to Week 52
Change from Baseline in mfERG
Time frame: Baseline up to Week 52
Change from Baseline in Retinal Thickness
Time frame: Baseline up to Week 52
Change from Baseline in Fundus Autofluorescence (FAF)
Time frame: Baseline up to Week 52
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 15 Oct 2026.
- 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.
Liping Yang, MD 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 Early Phase 1 study testing ZVS203e in people with Retinitis Pigmentosa, run by Peking University Third Hospital 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 12 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 15 Oct 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Liping Yang, MD (010-82266595, alexlipingyang@bjmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AEs and SAEs (time frame: Baseline up to Week 52). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Oct 2026.