This trial employs a multicenter, randomized, open-label, standard-of-care-controlled design and plans to enroll 50 patients with Type 2 SMA aged 2 to 12 years who have previously received nusinersen. The primary objective of the trial is to evaluate the efficacy of GC101 in treating Type 2 SMA. The secondary objectives are to assess the efficacy, safety, and pharmacokinetic (PK) profile of GC101 in treating Type 2 SMA.
Patients with a confirmed diagnosis of Type 2 5q-SMA through clinical phenotype and genetic testing.
Patients who have been receiving regular treatment with nusinersen for more than one year prior to screening.
Patients who have not received treatment with risdiplam within 2 months prior to screening and have no plans to receive risdiplam treatment within 12 months after enrollment.
Patients who can sit independently but cannot walk independently at the time of screening (according to the definitions of independent sitting and walking in the WHO-MGRS motor milestones scale), and have an HFMSE score of ≥10 points.
Patients with serum anti-AAV9 neutralizing antibody titers > 1:50 at the time of screening.
Patients who have received nusinersen treatment within 2 months prior to enrollment.
Patients with any medical conditions that may affect the interpretation of study results or pose a risk to the safety of the participants, including but not limited to organ dysfunction of any cause, acute infectious diseases, primary/acquired immunodeficiency diseases, severe cardiovascular/cerebrovascular diseases, gastrointestinal diseases, diabetes, known epilepsy, meningitis, seizure or convulsion history, or a family history of psychiatric disorders; and those with cerebrospinal fluid circulation disorders.
Patients with severe liver injury/hepatic insufficiency of any cause, including but not limited to alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥3 times the upper limit of normal (ULN); total bilirubin (TBil) ≥1.5 times the ULN.
Parallel
GC101 adeno-associated virus injection
GeneticSelf-complementary recombinant adeno-associated viral vector (scAAV) containing a single-stranded transgene encoding a codon-optimized human SMN1 gene
HFMSE score change from baseline
HFMSE Motor Function Assessment (Hammersmith Functional Motor Scale Expanded) is a standardized tool specifically designed to evaluate motor function in patients with spinal muscular atrophy (SMA). It includes 33 test items covering actions such as head control, sitting, standing, walking, stair climbing, jumping, as well as balance and coordination, providing a comprehensive assessment of motor function in the trunk and limbs. The maximum total score is 66 points, with higher scores indicating better motor capabilities.
HFMSE score change from baseline
The proportion of participants with an increase in HFMSE score of ≥3 points from baseline.
Minimal clinically important differences (MCID) were defined as an HFMSE score improvement of ≥3 points.
Changes in WHO-MGRS motor milestones from baseline.
WHO-MGRS (World Health Organization Multicenter Growth Reference Study) motor development milestones include: Sitting without support Standing with support Crawling on hands and knees Walking with support Standing alone Walking alone
RULM score change from baseline.
RULM Motor Function Assessment (Revised Upper Limb Module) is a standardized tool designed to evaluate upper limb function in patients with spinal muscular atrophy (SMA). A maximum total score is 37 points. Higher scores indicate better upper limb performance.
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