Spinal muscular atrophy
Conditions
Interventions
Low Dosing group:Intrathecal injection Low Dosing GCB-001
High Dosing group:Intrathecal injection High Dosing GCB-001
Sponsors
The Children's Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
2 Years to 12 Years
Inclusion criteria
Inclusion criteria: 1) When screening (when signing the informed consent form), age >= 2 years and 6 months and<18 months, are diagnosed with SMN1 double allele pathogenic mutation, have 2-4 copies of SMN2 gene, and meet the clinical diagnostic criteria for SMA 5qSMA; 3) Capable of sitting alone but has never acquired the ability to walk independently (according to HFMSE standards, sitting alone: able to maintain a sitting position without hand support and count to 3 or more; walking independently: able to walk 4 or more steps without assistance); 4) The guardians of the subjects are able to understand and willing to comply with the requirements and procedures of the research protocol, voluntarily participate and sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1) Researchers believe that gene replacement therapy may cause unnecessary risk of concomitant diseases, such as serious cardiovascular and cerebrovascular diseases, digestive tract diseases, liver and kidney dysfunction diseases, diabetes, known epilepsy, convulsions, convulsions or family history of psychosis; 2) Individuals who have participated in AAV gene therapy or have participated in or are currently participating in clinical trials of other SMA drugs; 3) Have received treatment with Nordenafil Sodium Injection within 4 months prior to administration; 4) Received treatment with risperidone within 15 days prior to administration; 5) Individuals who have been treated with ß 2 receptor agonists within 30 days prior to treatment (excluding inhaled salbutamol); 6) Subjects with allergic constitution, including those who are allergic or hypersensitive to prednisolone, other glucocorticoids or their excipients, and allergic to local anesthetics; 7) During the screening period, non-invasive ventilation support should be used for at least 12 hours per day; 8) When screening, the serum Anti-AAV9 neutralizing antibody titer is greater than 1:200; 9) Abnormal laboratory tests during the screening or baseline period, such as: a) Patients with liver dysfunction, i.e. ALT and AST >= 3 times the upper limit of normal (ULN); Total bilirubin (TBil) >= 1.5 times the upper limit of normal (ULN); b) Renal dysfunction: blood creatinine>normal value; c) Platelets (PLT)5/HP, urine protein (PRO) positive, red blood cell (RBC)>3/HP; 10) During the screening period, according to the health industry standards of the People's Republic of China (2023 growth standards for children under 7 years old), those who are 2 standard deviations below the average weight of children of the same age and gender (X-2SD) or who are not fed orally (such as those fed by nasal feeding); 11) During the screening period, invasive ventilators are used to support or pulse oximetry is less than 95% in a quiet and awake state; 12) Individuals who have contraindications for lumbar puncture surgery or intrathecal treatment, severe scoliosis (Cobb angle >= 40 degrees), or severe joint contracture deformities that may affect mobility assessment, and those planning spinal correction surgery during the observation period; 13) Patients who have active infections and require systemic medication treatment 2 weeks before a single intrathecal injection of GCB-001; 14) Patients with severe upper or lower respiratory tract infections 4 weeks prior to a single intrathecal injection of GCB-001; 15) Human immunodeficiency virus (HIV) antibody positive, or hepatitis B surface antigen positive, or hepatitis C antibody positive, or treponema pallidum antibody positive; 16) Those who receive the vaccine with an interval of less than 2 weeks between administration; 17) The researcher believes that it is not suitable to participate in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AE Rate within 12 months after dosing;AAV viral load and viral shedding after administration;Immunogenicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in Hammersmith Functional Motor Scale Expanded score in 12 month compared to baseline;Changes in Revised Upper Limb Module score in 12 month compare to baseline;Changes in Hammersmith Functional Motor Scale Expanded score >=3 in 12 month compared to baseline;Changes in RULM score >=2 in 12 month compared to baseline; | — |
Countries
China
Contacts
Public ContactShu Qiang
The Children's Hospital of Zhejiang University School of Medicine
Outcome results
None listed