Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 1 Patients

Prior treatment

• Patient who has participated in a previous gene therapy research trials;
• Patient who has received Nusinersen and Risdiplam treatment;
• Patient who has AAV9 neutralizing antibody titer ≥1:200;
• Vaccination less than 2 weeks before infusion of vector;
• Patient who has any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.
  • Note: Other protocol defined inclusion/exclusion criteria may apply.

Other illness

• Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
• Class IV patient based on Modified Ross Heart Failure Classification for Children;
• Patient with a history of glucocorticoid allergy;
• Presence of an untreated active infection requiring systemic antiviral therapy at any time during the screening period;

Lab values

• Abnormal laboratory values considered clinically significant, including gamma-glutamyl transferase(GGT), Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin \> 3x upper limit of normal (ULN), Hemoglobin (Hgb)\< 110 or \>150 g/L, platelet \<183x10\^9/L or 614x10\^9/L;

Other

• Patient who requires non-invasive ventilatory support averaging≥16 hours/day;
• Patient with a point mutation in SMN2 (c.859G\>C);
• Patient who requires non-invasive ventilatory support averaging≥16 hours/day at screening;
• Patient who use invasive ventilatory support or pulse oximetry \< 95% saturation while awake and calm at screening;
• Contraindication that would interfere with the lumbar puncture procedures;

• Six months of age and younger on day of vector infusion with Type 1 SAM as defined by the following features:
  • Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2;
  • Onset of disease before 6 months of age
• The 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.