The study will evaluate safety and efficacy of intrathecal delivery of GC101 gene therapy drug as a treatment of spinal muscular atrophy Type 3 (SMA 3) patients.
≥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;
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;
Single group
GC101
GeneticSelf-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter
Incidence of Treatment-Emergent Adverse Events
Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests
Change from baseline on Hammersmith Functional Motor Scale - Expanded (HFMSE) scores at Month 12
HFMSE consists of 33 activities that can be scored one of three ways: 0 for unable to perform, 1 for performs with modification/adaptation, and 2 for performs without modification.
The proportion of patients whose HFMSE improvement ≥ 3 points at Month 12
HFMSE ≥3 points：minimal clinically important differences (MCID) were considered for the outcomes:
Change from baseline on Revised Upper Limb Module (RULM) scores at Month 12
RULM is a 20-item evaluation of upper limb function primarily used for those with SMA who are non-ambulatory (young children through adults).
The proportion of patients whose Clinical Global Impression (CGI) is improved at Month 12
The Clinical Global Impressions (CGI) is a widely used assessment tool in clinical practice, particularly for evaluating the severity of a patient's illness and the effectiveness of treatments. The CGI consists of two primary components: CGI-Severity (CGI-S): This scale measures how ill a patient is at a given time, with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). It reflects the clinician's overall view of the patient's mental health status based on all available information, including symptoms, behavior, and functional impairments experienced in the past week. CGI-Improvement (CGI-I): This scale rates the change in the patient's condition compared to a baseline state, prior to the initiation of treatment. It uses a seven-point scale where 1 indicates "very much improved" and 7 indicates "very much worse." The CGI-I captures the overall change in the patient's clinical state since the start of treatment.
The proportion of patients whose Motor Function Measure (MFM) is improved or maintained at Month 12
The Motor Function Measure (MFM) is a validated scale specifically designed to assess motor function in individuals with neuromuscular disorders like Spinal Muscular Atrophy (SMA). It consists of 32 items that are scored on a 4-point Likert scale, reflecting a person's maximum ability to perform tasks without assistance.
Change from baseline of Forced Vital Capacity (FVC) at Month 12 ( for patients > 6 years)
Change from baseline of Forced Expiratory Volume in 1 Second (FEV1) at Month 12 ( for patients > 6 years)
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