Safety and Efficacy Evaluation of GC101 Gene Therapy Via Intrathecal (IT) Injectionin the Treatment of Patients With Type 2 Spinal Muscular Atrophy (SMA) - Phase III
GC101 adeno-associated virus injection: Self-complementary recombinant adeno-associated viral vector (scAAV) containing a single-stranded transgene encoding a codon-optimized human SMN1 gene
Study summary
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.
Eligibility
Sex
ALL
Min age
2 Years
Max age
12 Years
Healthy volunteers
No
Inclusion Criteria:
* 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 and/or their legal guardians are able to understand and are willing to comply with the requirements and procedures of the trial protocol, and voluntarily participate and sign the informed consent form
Exclusion Criteria:
* 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.
* Patients deemed by the investigator to have contraindications to glucocorticoid use, such as severe hypertension, diabetes, systemic infectious diseases, fungal infections, glaucoma, osteoporosis, peptic ulcer disease, tuberculosis, etc.
* Patients with contraindications to lumbar puncture or intrathecal injection therapy.
* Patients with any medical conditions that may affect the assessment of motor function, such as severe scoliosis, severe joint contracture deformities, planned spinal correction surgery during the trial period, severe osteoporosis, or a history of fractures.
* Patients positive for hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV) antibodies, hepatitis C virus (HCV) antibodies, or syphilis antibodies.
* Patients who have received vaccinations within 2 weeks prior to dosing.
* Patients who have previously received gene therapy or participated in any clinical trial within 3 months prior to screening.
* Patients deemed by the investigator to be unsuitable for participation in this study.
Primary outcome measure(s)
HFMSE score change from baseline — 52 weeks 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.
Trial sites (7)
Facility
City
Region
Status
The Seventh Medical Center of Chinese PLA General Hospital
Beijing
China
Recruiting
Children's Medical Center of Peking University First Hospital
Beijing
China
Recruiting
Beijing Children's Hospital, Capital Medical University
Beijing
China
Recruiting
National Children's Medical Center,Shanghai Jiaotong University
Shanghai
China
Recruiting
Shenzhen Children's Hospital
Shenzhen
China
Recruiting
Children's Hospital of Soochow University
Suzhou
China
Recruiting
Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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