Gene therapy for patients with X-linked retinoschisis

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 study is testing a new gene therapy called ZM-01 to see if it can improve vision and retinal health in boys aged 3 to 18 with X-linked retinoschisis.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 3 Years to 18 Years
• Sex: Male
• Sponsor: Zhongmou Therapeutics (Industry-sponsored)
• Locations: 1 site (Xiaogan, Hubei)
• Trial ID: NCT06066008 on ClinicalTrials.gov

What this trial studies

This trial evaluates the safety and efficacy of a novel gene therapy, ZM-01, for treating X-linked retinoschisis, a rare inherited retinal disease caused by mutations in the RS1 gene. The study involves administering unilateral intravitreal injections of ZM-01 to male patients aged 3 to 18 years who have been diagnosed with XLRS. The trial aims to assess the treatment's impact on visual function and overall retinal health. Participants will be monitored for safety and efficacy outcomes following the injection.

Who should consider this trial

Good fit: Ideal candidates for this study are male patients aged 3 to 18 years with a confirmed diagnosis of X-linked retinoschisis and specific visual acuity criteria.

Not a fit: Patients who do not have X-linked retinoschisis or those with better visual acuity than specified may not benefit from this study.

Why it matters

Potential benefit: If successful, this gene therapy could provide a new treatment option for patients suffering from X-linked retinoschisis, potentially improving their visual function.

How similar studies have performed: While gene therapy approaches for retinal diseases are emerging, this specific application for X-linked retinoschisis is novel and has not been extensively tested in prior studies.

Eligibility criteria

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

Where this trial is running

Xiaogan, Hubei

• Wuhan University Renmin Hospital affiliated with Hanchuan Hospital — Xiaogan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Pei Cao

Conditions X-linked Retinoschisis; gene therapy; AAV; RS1