safety and tolerability study of gene editing drug zvs203e in participants with retinitis pigmentosa

Conditions: Retinitis Pigmentosa

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 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.

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.

Keywords: gene editing retinitis pigmentosa rho raav