X-linked Retinoschisis
Conditions
Keywords
gene therapy, AAV, RS1
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.
Interventions
DRUGZM-01-L
rAAV-hRS1 intravitreal injection of low dose
DRUGZM-01-H
rAAV-hRS1 intravitreal injection of high dose
Sponsors
Zhongmou Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
3 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events and serious adverse events | 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. |
| Change in best corrected visual acuity (BCVA) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events and serious adverse events | 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. |
| Change in Quality of Life | baseline to month 9, 12 | Quality of Life will be measured using Pediatric Eye Questionnaire (PedEyeQ) or other similar questionnaires before and after treatment |
| Change in best corrected visual acuity (BCVA) | 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. |
| Change in visual field | 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. |
| Change in electrophysiology result | 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). |
| Anti-AAV neutralizing antibody titer, Anti-RS1 neutralizing antibody titer | 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. |
| Change in the retina cavity assessed by macular OCT | 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. |
Countries
China
Contacts
STUDY_CHAIRYin Shen, PhD
Zhongmou Theraputics
Outcome results
None listed