- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06066008
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Pei Cao
- Phone Number: +86 18707134160
- Email: zmt@simbaeye.com
Study Locations
-
-
Hubei
-
Xiaogan, Hubei, China
- Recruiting
- Wuhan University Renmin Hospital affiliated with Hanchuan Hospital
-
Contact:
- Pei Cao
- Phone Number: +86 18707134160
- Email: caopei813@163.com
-
Principal Investigator:
- Guangtao Sun, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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.
Exclusion Criteria:
Subjects who meet any of the following exclusion criteria before enrollment were excluded from the study
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: group 1
IVT administration of a single low dose ZM-01 injection
|
rAAV-hRS1 intravitreal injection of low dose
Other Names:
|
Experimental: group 2
IVT administration of a single high dose ZM-01 injection
|
rAAV-hRS1 intravitreal injection of high dose
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events and serious adverse events
Time Frame: baseline to day 7, month 1, 2
|
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)
Time Frame: baseline to day 7, month 1, 2
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events and serious adverse events
Time Frame: baseline to month 3, 4, 6, 9, 12
|
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 month 3, 4, 6, 9, 12
|
Change in Quality of Life
Time Frame: baseline to month 9, 12
|
Quality of Life will be measured using Pediatric Eye Questionnaire (PedEyeQ) or other similar questionnaires before and after treatment
|
baseline to month 9, 12
|
Change in best corrected visual acuity (BCVA)
Time Frame: baseline to month 3, 4, 6, 9, 12
|
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 month 3, 4, 6, 9, 12
|
Change in visual field
Time Frame: baseline to month 1, 2, 3, 4, 6, 9, 12
|
Visual field will be assessed by Humphrey perimetry, changes in VFI, MD, PSD will be analyzed.
|
baseline to month 1, 2, 3, 4, 6, 9, 12
|
Change in electrophysiology result
Time Frame: baseline to month 1, 2, 3, 4, 6, 9, 12
|
The ERG measurement will be performed based on the standards of international society for clinical electrophysiology of vision (ISCEV).
|
baseline to month 1, 2, 3, 4, 6, 9, 12
|
Anti-AAV neutralizing antibody titer, Anti-RS1 neutralizing antibody titer
Time Frame: baseline to day 1, 7 and month 1, 2
|
Peripheral blood samples were collected from each subjects to measure the AAV8 antibody levels and virus titers in the peripheral blood.
|
baseline to day 1, 7 and month 1, 2
|
Change in the retina cavity assessed by macular OCT
Time Frame: baseline to day 7, month 1, 2, 3, 4, 6, 9, 12
|
Optical coherence tomography (OCT) of the macula was performed in both eyes of each participant at each visit.
|
baseline to day 7, month 1, 2, 3, 4, 6, 9, 12
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Yin Shen, PhD, Zhongmou Theraputics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ZM-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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