Safety and Efficacy Study of Novel Gene Therapy ZM-01 for X-linked Retinoschisis Patients

Prospective, Dose-Escalating, Investigator Initiated Trial to Evaluate the Safety and Efficacy of ZM-01 in 3-18 Year-old Male Subjects With X-linked Retinoschisis

This trial is meant to evaluate the safety and efficacy of ZM-01 of X-linked retinoschisis. Unilateral intravitreal injections (IVT) will be given into the subject's Study Eye.

X-linked retinoschisis (XLRS) is a rare, inherited retinal disease caused by mutations in the RS1 gene. Individuals affected by XLRS often experience progressive visual impairment from a young age, potentially leading to legal blindness. There is currently no established clinical treatment available. We developed an innovative adeno-associated virus (AAV)-based gene therapy for individuals with XLRS. Six to nine subjects with XLRS received a single unilateral intravitreal injection of ZM-01 at ascending doses.

Inclusion Criteria:

Subjects who meet all of the following criteria will be enrolled into the study

1. Diagnosis of X-linked retinoschisis consistent with the presence of RS1 gene mutation

2. Male, aged between 3 and 18 years old, in overall good health except for XLRS condition

3. Capable of undergoing visual and retinal function assessment.

4. The visual acuity of the study eye not better than: 0.4 (68 ETDRS letters equivalent)

5. No carbonic anhydrase inhibitors have been used at present and for 3 months before treatment

6. Laboratory tests meet the following criteria:

   1. Hemoglobin ≥ 11.0 g/dL
   2. White blood cell counts ranged from 3,300 to 12,000 cells /mm³;
   3. Platelet count 125,000-550,000 /mm³;
   4. Alanine aminotransferase (ALT) is not higher than 1.5 times the upper limit of the normal range of laboratory tests;
   5. Serum creatinine was no higher than 1.1 times the upper limit of the normal range for laboratory tests;
   6. Prothrombin time (PT) ≤14.5 seconds and partial thromboplastin time (PTT) ≤ 36.0 seconds.

7. Willing to discontinue aspirin, aspirin-containing products, and any other medications that may alter clotting function at least 7 days before dosing.

8. Be able to understand and sign informed consent.

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria before enrollment were excluded from the study

1. Previously received any AAV gene therapy
2. The following mutations in RS1 gene: R141H, C59S or C223S
3. Pre-existing eye conditions that cause severe vision loss or increase the risk of intravitreal injections (e.g., advanced glaucoma, uveitis, or severe retinal detachment)
4. Ocular diseases in which there is opacity of the lens, cornea, or other media, hindering adequate observation and examination of the retina
5. Use anticoagulant or antiplatelet drugs within 7 days before dosing
6. Use any experimental drug within 3 months prior to registration
7. Presented any situation that causes the investigator to believe the subject might not adhere to the study protocol or that participation might pose an unacceptable risk to the subject