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

The purpose of this trial is to evaluate safety and efficacy of gene therapy drug GC101 in SMA 1 patients. Open-label, dose-escalation clinical trial 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 on various time points.

The primary analysis for efficacy will be assessed when all patients reach 18 months of age on the motor milestone of sit unassisted for at least 10 seconds.

Inclusion criteria

• 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.

Exclusion criteria

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