Gene editing treatment for Retinitis Pigmentosa

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

This study is testing a gene editing treatment called ZVS203e to see if it can safely help people with Retinitis Pigmentosa caused by a specific gene mutation.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University Third Hospital (other)
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT05805007 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and efficacy of a gene editing drug called ZVS203e administered through a subretinal injection in participants with Retinitis Pigmentosa caused by a specific RHO gene mutation. It is a single-arm, open-label study that will enroll up to 9 participants, who will receive escalating doses of the drug. The study aims to measure the safety and effectiveness of the treatment, as well as the characteristics of the gene delivery vector.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed RHO gene mutation and specific visual acuity criteria.

Not a fit: Patients with other significant eye conditions or those who have received recent treatments that could interfere with the study will not benefit.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with Retinitis Pigmentosa, potentially improving their vision.

How similar studies have performed: While gene editing approaches are emerging, this specific application in Retinitis Pigmentosa is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* 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;

Exclusion Criteria:

* 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；
* 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.

Where this trial is running

Beijing, Beijing

• Peking University Third Hospital — Beijing, Beijing, China (RECRUITING)

Study contacts

• Principal investigator: Liping Yang, MD — Peking University Third Hospital
• Study coordinator: Liping Yang, MD

Conditions: Retinitis Pigmentosa, gene editing, retinitis pigmentosa, RHO, rAAV