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

NCT ID: NCT06066008

Last Updated: 2024-02-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-25
• Study Completion Date: 2027-10-31

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.

Conditions

X-linked Retinoschisis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

group 1

IVT administration of a single low dose ZM-01 injection

Group Type: EXPERIMENTAL

ZM-01-L

Intervention Type: DRUG

rAAV-hRS1 intravitreal injection of low dose

group 2

IVT administration of a single high dose ZM-01 injection

Group Type: EXPERIMENTAL

ZM-01-H

Intervention Type: DRUG

rAAV-hRS1 intravitreal injection of high dose

Interventions

ZM-01-L

rAAV-hRS1 intravitreal injection of low dose

Intervention Type: DRUG

ZM-01-H

rAAV-hRS1 intravitreal injection of high dose

Intervention Type: DRUG

Other Intervention Names

rAAV-hRS1; rAAV-hRS1

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

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Zhongmou Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yin Shen, PhD

Role: STUDY_CHAIR

Zhongmou Theraputics

Locations

Wuhan University Renmin Hospital affiliated with Hanchuan Hospital

Xiaogan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Pei Cao

Role: CONTACT

zmt@simbaeye.com

+86 18707134160

Facility Contacts

Pei Cao

Role: primary

caopei813@163.com

+86 18707134160

Other Identifiers

ZM-01

Identifier Type: -

Identifier Source: org_study_id