Gene therapy for treating Type 2 Spinal Muscular Atrophy

A 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)

This study is testing a new gene therapy called GC101 to see if it can help children aged 2 to 12 with Type 2 Spinal Muscular Atrophy feel better compared to their current treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 2 Years to 12 Years
• Sex: All
• Sponsor: GeneCradle Inc (Industry-sponsored)
• Locations: 7 sites (Beijing and 6 other locations)
• Trial ID: NCT06971094 on ClinicalTrials.gov

What this trial studies

This trial evaluates the safety and efficacy of GC101 gene therapy administered via intrathecal injection in children aged 2 to 12 years with Type 2 Spinal Muscular Atrophy (SMA) who have previously received nusinersen. It is a multicenter, randomized, open-label, standard-of-care-controlled study involving 50 participants. The trial compares the effects of a single injection of GC101 against continued treatment with nusinersen, focusing on efficacy, safety, and pharmacokinetics. Participants will be randomly assigned to either the treatment or control group.

Who should consider this trial

Good fit: Ideal candidates are children aged 2 to 12 years with a confirmed diagnosis of Type 2 SMA who have been on nusinersen treatment for over a year.

Not a fit: Patients who have high levels of anti-AAV9 neutralizing antibodies or have received risdiplam treatment recently may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option that may improve motor function in children with Type 2 SMA.

How similar studies have performed: Other studies involving gene therapy for SMA have shown promising results, indicating potential for success in this approach.

Eligibility criteria

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.

Where this trial is running

Beijing and 6 other locations

• 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 — Wuhan, China (Recruiting)

Study contacts

• Study coordinator: GeneCradle, Inc China

Conditions SMA - Spinal Muscular Atrophy; SMA, type II, AAV gene therapy; Genecradle