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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified May 2025 by GeneCradle Inc
Sponsor
GeneCradle Inc
Information Provided by (Responsible Party)
GeneCradle Inc
Clinicaltrials.gov Identifier
NCT06971094
Other Study ID Numbers:
JLJY-GC101-SMA-011
First Submitted
May 5, 2025
First Posted
May 13, 2025
Last Update Posted
June 4, 2025
Last Verified
May 2025

ClinicalTrials.gov processed this data on June 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

The trial is divided into two groups: one group will receive a single intrathecal injection of GC101 at a dose of 1.2E+14 vg per person and discontinue their previous standard-of-care treatment with nusinersen; the other group will continue their previous standard-of-care treatment with nusinersen. Participants will be randomly assigned to the trial group or the control group in a 1:1 ratio.

Condition or DiseaseIntervention/Treatment
SMA - Spinal Muscular Atrophy
Genetic: GC101 adeno-associated virus injection

Study Design

Study TypeInterventional
Actual Enrollment50 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Multicenter, Randomized, Open-Label, Standard-of-Care-Controlled, Phase III Clinical Trial to Evaluate the Safety and Efficacy of Intrathecal (IT) Injection of GC101 Adeno-Associated Virus Injection in the Treatment of Patients With Type 2 Spinal Muscular Atrophy (SMA)
Study Start DateMay 26, 2025
Actual Primary Completion Date7mos 2w from now
Actual Study Completion Date7mos 2w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
GC101
single dose of GC101 at dosage of 1.2E+14 vg per person via intrathecal injection
Genetic: 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
Control
Participants will continue to receive treatment according to their previous standard-of-care regimen with nusinersen.

Outcome Measures

Primary Outcome Measures
  1. 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.
Secondary Outcome Measures
  1. HFMSE score change from baseline
  2. 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.
  3. 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
  4. 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.
  5. SMAIS score change from baseline.
    Spinal Muscular Atrophy Independence Scale （SMAIS）is a patient- and caregiver-reported outcome measure designed to assess the level of assistance required by individuals with Type 2 and non-ambulant Type 3 spinal muscular atrophy (SMA) to perform activities of daily living. Higher scores indicate greater independence, with a range from 0 to 44
  6. The incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs).

Eligibility Criteria

Ages Eligible for Study(Child)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsGeneCradle Inc
Locations
The Seventh Medical Center of Chinese PLA General Hospital | Beijing , China, 100700Children's Medical Center of Peking University First Hospital | Beijing , China, 102699Beijing Children's Hospital, Capital Medical University | Beijing , China, National Children's Medical Center，Shanghai Jiaotong University | Shanghai , China, 200127Shenzhen Children's Hospital | Shenzhen , China, Children's Hospital of Soochow University | Suzhou , China, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology | Wuhan , China, 430015