Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 3 Patients

The purpose of this trial is to evaluate safety and efficacy of gene therapy drug GC101 in SMA 3 patients. Open-label, dose-escalation clinical trials of GC101 will be conducted in multiple centers in China.

GC101 will be administrated intrathecally. Short-term safety will be evaluated in 52 weeks and enter long-term follow-up study of 5 years at will. Patients will be tested at baseline and followed up at various time points.

The primary analysis for efficacy will be assessed at 12 months after treatment with GC101 on the changes from baseline HFMSE (Hammersmith Functional Motor Scale Expanded) and RULM（Revised Upper Limb Module) scores for patients of age ≥ 6 years old.

Inclusion criteria

• ≥2 years of age on the day of signing the informed consent form;
• Genetic and clinical diagnosis of type 3 SMA with bi-allelic deletion of SMN1 of 5qSMA;
• Hammersmith Functional Motor Scale - Expanded (HFMSE) score is between 10 and 54 at screening;
• Female patients of childbearing age who are pregnant or lactating, as well as all enrolled patients （both male and female), should take effective contraceptive measures within 6 months after the treatment;
• Patients or patient's legal guardian(s) must be able to understand the purpose and risks of the study and voluntarily provide signed and dated informed consent prior to any study-related procedures being performed.

Exclusion criteria

• Patient who has participated in any previous gene therapy research trials;
• Patient who has AAV9 neutralizing antibody titer ≥1:200;
• Patient who has received Nusinersen within 120 days and Risdiplam within 15 days before treatment;
• Patient who requires invasive or non-invasive ventilatory support averaging≥16 hours/day at screening;
• SMN2 copy numbers >4；
• Patient who needs nasal or gastric tube feeding for eating;
• Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
• Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
• Severe contractures at screening that interfere with either the ability to attain/demonstrate functional measures or with the ability to receive intrathecal (IT) dosing;
• Patient who has other serious diseases, such as severe cardiovascular and cerebrovascular diseases, digestive system diseases, urinary system diseases, endocrine system diseases, hematological diseases, immune system diseases, nervous system diseases (including but not limited to epilepsy, meningitis, history of convulsions or seizures, cerebrospinal fluid circulation disorders), and mental illnesses, etc.;
• Patient with previous injuries (such as upper or lower limb fractures) or surgical operations that have not fully recovered or reached a stable state;
• Vaccination no longer than 2 weeks before treatment;
• Patient who has any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in the study.