X-linked retinoschisis
Conditions
Interventions
Phase I. Group 1:JWK002 injection, 3×10^10 vg/eye
Phase I. Group 2:JWK002 injection,1×10^11 vg/eye
Phase II. Treatment group:JWK002
Phase II. Control group:None
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
Male
Age
4 Years to 64 Years
Inclusion criteria
Inclusion criteria: Participants must meet all of the following criteria to be considered for enrollment: 1. The subject (or the subject’s legal guardian for pediatric participants) must voluntarily sign a written informed consent form prior to any study-related procedures and must be willing and able to comply with the requirements of the study protocol. 2. Age and Gender: • Phase I: Subjects aged >=4 years and =64 years. • Phase II, Cohort 1: Subjects aged >=4 years and =18 years and <=64 years. • All ages are calculated based on the date of signing the informed consent form. • Male subjects only. 3. Clinical diagnosis of X-linked retinoschisis (XLRS) confirmed by the presence of a pathogenic RS1 gene mutation, as determined by genetic testing, with no additional mutations known to cause other ocular diseases. 4. Best-corrected visual acuity (BCVA) in the treated eye must be measurable using an ETDRS chart and must not exceed 63 letters (equivalent to Snellen 20/63). 5. Participants of reproductive potential whose partners are also of reproductive potential must agree to use effective contraception for at least 12 months following the delivery of JWK002.
Exclusion criteria
Exclusion criteria: Participants will be excluded from the study if they meet any of the following criteria: 1. The study eye has any ocular disease or history (other than XLRS) that may lead to central vision loss or pose specific risks (e.g., optic neuropathy, glaucoma, uveitis, retinal tear, retinal detachment, retinal atrophy, vitreous hemorrhage, retinal neovascularization, etc.). 2. The study eye has lens, corneal, or other media opacities and/or pupillary abnormalities that interfere with adequate visualization and examination of the retina. 3. The study eye has undergone any intraocular surgery within 4 weeks prior to screening. 4. The study eye has any condition deemed unsuitable for subretinal injection surgery by the investigator, such as large bullous schisis cavities or bullous retinal detachment, or has previously undergone vitrectomy with residual intraocular tamponade (e.g., silicone oil or gas). 5. Evidence of active intraocular, periocular, or ocular surface infection or inflammation in either eye at screening, including infectious blepharitis, keratitis, scleritis, or conjunctivitis. 6. History of idiopathic or autoimmune uveitis in either eye. 7. Inability to complete assessments of visual and retinal function, including BCVA, OCT, ERG, static visual field, and microperimetry. 8. Use of carbonic anhydrase inhibitors (systemic or ocular in the study eye) within 4 weeks prior to screening. 9. History of severe allergy or known hypersensitivity to any treatment or medication used in this study protocol. 10. Diabetes with poor glycemic control (HbA1c >= 8%). 11. Abnormal liver or renal function: a. Liver: ALT and/or AST > 2.5 × upper limit of normal (ULN), or total bilirubin (TBIL) > 1.5 × ULN; b. Kidney: serum creatinine > 1.5 × ULN. 12. Coagulation abnormalities: Prothrombin time (PT) > 1.5 × ULN, or activated partial thromboplastin time (APTT) > 1.5 × ULN. 13. Any active systemic infection requiring systemic therapy that may affect study participation or outcomes, as judged by the investigator, such as:Hepatitis B surface antigen (HBsAg) positive with HBV DNA > ULN; Hepatitis C virus (HCV) antibody positive with HCV RNA > ULN; Positive Treponema pallidum (syphilis) antibody; HIV antigen/antibody combo test positive and confirmed HIV infection. 14. Diagnosed systemic autoimmune disease (e.g., ankylosing spondylitis, systemic lupus erythematosus), or current treatment with immunosuppressive or immunostimulatory agents. 15. Presence of any uncontrolled clinical condition (e.g., AIDS, active hepatitis, severe psychiatric, neurological, cardiovascular, or respiratory disease) that could interfere with study participation. 16. History of malignancy, except in the following cases: a. Malignancies that have been cured and have not recurred within the past 5 years; b. Malignancies that have been cured and are considered unlikely to recur by the investigator, such as non-melanoma skin cancer or superficial bladder cancer. 17. Use of antiviral medications (excluding topical ocular use) from 2 weeks before screening until enrollment, or planned use within 1 month after administration of JWK002. 18. Receipt of a live vaccine within 4 weeks prior to the initiation of study-specified immunosuppressive treatment. 19. Prior exposure to any form of AAV gene therapy. 20. Participation in any clinical trial involving drugs (excluding vitamins and minerals) and having received the investigational product within 4 weeks prior to screening (or within 5 half-l
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| adverse event, AE;dose-limiting toxicity, DLT; | — |
Secondary
| Measure | Time frame |
|---|---|
| Best Corrected Visual Acuity, BCVA;Central retinal thickness, CRT;Retinal structural morphology;Dark adaptation 3.0 a-wave amplitude, b-wave amplitude, and b/a ratio.;Contrast sensitivity;Mean sensitivity;VFQ-25 score;CVAQC score; | — |
Countries
China
Contacts
Public ContactFang Lu
West China Hospital, Sichuan University
Outcome results
None listed