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

NCT06066008 | Completed Early Phase 1

• 1 other identifier: ZM-01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

X-linked Retinoschisis

Keywords

gene therapy; AAV; RS1

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events and serious adverse events

  An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment. A serious adverse event (SAE) is any untoward medical occurrence at any dose that leading to the following: Results in death; Life-threatening, refers to an event in which the patient is at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe; Significant or permanent disability/incapacity, where disability refers to a serious disruption and damage of a person's ability to perform normal life functions; Requires inpatient hospitalization or prolongation of existing hospitalization; Congenital anomaly or birth defect; Other medically important events.

  baseline to day 7, month 1, 2

• Change in best corrected visual acuity (BCVA)

  BCVA of both eyes will be assessed using the early treatment of diabetic retinopathy study (ETDRS) chart or tumbling "E" chart. This approach was chosen to facilitate visual acuity testing in children who cannot recognize letters, which was more appropriate for this study.

  baseline to day 7, month 1, 2

Secondary Outcomes (7)

• Incidence of adverse events and serious adverse events

  baseline to month 3, 4, 6, 9, 12

• Change in Quality of Life

  baseline to month 9, 12

• Change in best corrected visual acuity (BCVA)

  baseline to month 3, 4, 6, 9, 12

• Change in visual field

  baseline to month 1, 2, 3, 4, 6, 9, 12

• Change in electrophysiology result

  baseline to month 1, 2, 3, 4, 6, 9, 12

Study Arms (2)

group 1

EXPERIMENTAL

IVT administration of a single low dose ZM-01 injection

Drug: ZM-01-L

group 2

EXPERIMENTAL

IVT administration of a single high dose ZM-01 injection

Drug: ZM-01-H

Interventions

ZM-01-L DRUG

rAAV-hRS1 intravitreal injection of low dose

Also known as: rAAV-hRS1

group 1

ZM-01-H DRUG

rAAV-hRS1 intravitreal injection of high dose

Also known as: rAAV-hRS1

group 2

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects who meet all of the following criteria will be enrolled into the study
• Diagnosis of X-linked retinoschisis consistent with the presence of RS1 gene mutation
• Male, aged between 3 and 18 years old, in overall good health except for XLRS condition
• Capable of undergoing visual and retinal function assessment.
• The visual acuity of the study eye not better than: 0.4 (68 ETDRS letters equivalent)
• No carbonic anhydrase inhibitors have been used at present and for 3 months before treatment
• Laboratory tests meet the following criteria:
• Hemoglobin ≥ 11.0 g/dL
• White blood cell counts ranged from 3,300 to 12,000 cells /mm³;
• Platelet count 125,000-550,000 /mm³;
• Alanine aminotransferase (ALT) is not higher than 1.5 times the upper limit of the normal range of laboratory tests;
• Serum creatinine was no higher than 1.1 times the upper limit of the normal range for laboratory tests;
• Prothrombin time (PT) ≤14.5 seconds and partial thromboplastin time (PTT) ≤ 36.0 seconds.
• Willing to discontinue aspirin, aspirin-containing products, and any other medications that may alter clotting function at least 7 days before dosing.
• Be able to understand and sign informed consent.

You may not qualify if:

• Previously received any AAV gene therapy
• The following mutations in RS1 gene: R141H, C59S or C223S
• 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)
• Ocular diseases in which there is opacity of the lens, cornea, or other media, hindering adequate observation and examination of the retina
• Use anticoagulant or antiplatelet drugs within 7 days before dosing
• Use any experimental drug within 3 months prior to registration
• 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

Sponsors & Collaborators

• Zhongmou Therapeutics: lead

Study Sites (1)

Wuhan University Renmin Hospital affiliated with Hanchuan Hospital

Xiaogan, Hubei, China

Location

MeSH Terms

Conditions

Retinoschisis

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Officials

• Yin Shen, PhD

  Zhongmou Theraputics

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 4, 2023
• Study Start: September 25, 2022
• Primary Completion: October 31, 2023
• Study Completion: January 31, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)