Safety and Efficacy of a Single Subretinal Injection of JWK002 Gene Therapy in Subjects With X-linked Retinoschisis(XLRS)

Clinical Study on the Safety and Efficacy of JWK002 Injection Administered as a Single Subretinal Injection in Subjects With X-linked Retinoschisis

This trial is to evaluate the safety and efficacy of JWK002 treatment of X-linked retinoschisis(XLRS). This study will enroll subjects aged 5-18 years old to receive a sub-retinal injection of JWK002.

Study Overview

• Status: Recruiting
• Conditions: X Linked Retinoschisis
• Intervention / Treatment: Drug: JWK002

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Licong Liang; Email: 932968425@qq.com
• Study Contact Backup: Name: Kaiqin She; Email: shekaiqin@wchscu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610023
      • Recruiting
      • West China Hospital
      • Contact: Licong Liang; Email: 932968425@qq.com
      • Contact: Fang Lu; Email: lufang@wchscu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Fully understand the purpose and requirements of the trial, voluntarily participate in the clinical trial and sign the informed consent, and be able to cooperate with the testing required in various studies according to the requirements of the program;
2. Male, ≥5 years old and < 18 years old (subject to the date of signing the informed consent);
3. Clinically diagnosed XLRS, identified by genetic testing as RS1 gene mutation, and do not carry other mutations causing ophthalmic genetic diseases;
4. Best corrected visual acuity (BCVA) of the study eye ≤63 letters (equivalent to Snellen 20/63); Best corrected visual acuity (BCVA) ≥34 letters (equivalent to Snellen 20/200).

Exclusion Criteria:

1. Carbonic anhydrase inhibitor treatment within 3 months;
2. The presence of other conditions in the study eye that may cause vision loss (e.g., atrophy of the optic nerve, advanced glaucoma, uveitis, the presence of vesicular splitting chambers or vesicular retinal detachment that may affect the subretinal injection operator);
3. Those who study the retinal observation and examination caused by lens, cornea or other refractive interstitial turbidity;
4. There are eye conditions affecting subretinal injection or eye conditions affecting the determination of the study endpoint;
5. Patients who had undergone internal eye surgery within 6 months;
6. Patients with AAV8 neutralizing antibody titer ≥1:1000;
7. Have previously received any gene therapy or cell therapy;
8. fertile subjects are unwilling to use contraception;
9. The presence of any of the following: an active infection that the investigator believes may affect the patient's participation in the study or affect the study results that requires systematic treatment; Hepatitis B surface antigen positive, hepatitis B virus deoxyribonucleic acid (HBV DNA) copy number > ULN; Hepatitis C virus (HCV) antibody positive and HCV-RNA copy number >ULN; Treponema pallidum antibody positive; Positive for human immunodeficiency virus (HIV) antibodies;
10. Malignant tumors (basal cell or squamous cell skin cancer) were diagnosed within 5 years prior to screening;
11. has or has had a systemic immune system disease;
12. Laboratory values considered to be clinically significant were abnormal: alanine and/or aspartate transaminase >2.5×ULN, total bilirubin >1.5×ULN, serum creatinine >1.5×ULN, prothrombin time ≥1.5×ULN, activated partial thromboplastin time ≥1.5×ULN; (13) have a severe allergy or a known allergy to the drugs used in the treatment or examination in the study protocol, including the investigational drug allergy;

(14) Other situations that the investigator considers inappropriate for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JWK002 at Low Dose Group; Subretinal injection low dose of JWK002 in one eye	Drug: JWK002; Subretinal administration of gene therapy vector JWK002 to one eye.
Experimental: JWK002 at Medium Dose Group; Subretinal injection medium dose of JWK002 in one eye	Drug: JWK002; Subretinal administration of gene therapy vector JWK002 to one eye.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety(Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)	The primary outcome measures are safety, determined by the number of ocular and non-ocular Study Drug-related adverse events (SDAE), treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).	baseline to day 7, day 14, month 1, 3, 6, 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best corrected visual acuity (BCVA)	Visual acuity of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS)	baseline to day 7, day 14, month 1, 2, 3, 6, 12
Full-field electroretinogram(ff-ERG)	The ERG measurement will be performed based on the standards of international society for clinical electrophysiology of vision (ISCEV).	baseline to month 1, 3, 6, 12
Macular structure as assessed by swept source optical coherence tomography	Change in swept source optical coherence tomography(SS-OCT)	baseline to month 1, 3, 6, 12
Visual field	Change in visual field assessed by Humphrey perimetry	baseline to month 1, 3, 6, 12

Collaborators and Investigators

• Sponsor: West China Hospital
• Investigators: Principal Investigator: Fang Lu, lufang@wchscu.cn

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Estimated): November 30, 2033
• Study Completion (Estimated): November 30, 2033

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: March 28, 2024
• First Posted (Actual): April 3, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: X Linked Retinoschisis
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Retinoschisis
• Other Study ID Numbers: 2023-1479

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No