Clinical trial NCT06066008: Safety and Efficacy Study of Novel Gene Therapy ZM-01 for X-linked Retinoschisis Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: X-linked Retinoschisis
Keywords: gene therapy
AAV
RS1
Lead sponsor: Zhongmou Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-10-04
Enrollment: 9
Sex: MALE
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

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

Primary outcomes:
measure: Incidence of adverse events and serious adverse events
timeFrame: baseline to day 7, month 1, 2
measure: Change in best corrected visual acuity (BCVA)
timeFrame: baseline to day 7, month 1, 2
Secondary outcomes:
measure: Incidence of adverse events and serious adverse events
timeFrame: baseline to month 3, 4, 6, 9, 12
measure: Change in Quality of Life
timeFrame: baseline to month 9, 12
measure: Change in best corrected visual acuity (BCVA)
timeFrame: baseline to month 3, 4, 6, 9, 12
measure: Change in visual field
timeFrame: baseline to month 1, 2, 3, 4, 6, 9, 12
measure: Change in electrophysiology result
timeFrame: baseline to month 1, 2, 3, 4, 6, 9, 12
measure: Anti-AAV neutralizing antibody titer, Anti-RS1 neutralizing antibody titer
timeFrame: baseline to day 1, 7 and month 1, 2
measure: Change in the retina cavity assessed by macular OCT
timeFrame: baseline to day 7, month 1, 2, 3, 4, 6, 9, 12
Other outcomes:
Locations:
city: Xiaogan
country: China
facility: Wuhan University Renmin Hospital affiliated with Hanchuan Hospital
state: Hubei
Study officials:
affiliation: Zhongmou Theraputics
name: Yin Shen, PhD
role: STUDY_CHAIR
References: