Gene therapy for treating spinal muscular atrophy type 3

A Multi-center, Open Label, Single-arm, Dose Ascending Clinical Trial for Evaluation of Safety and Efficacy of Gene Therapy Drug GC101 in the Treatment of Spinal Muscular Atrophy (SMA) Type 3 Patients

This study is testing a new gene therapy for people with spinal muscular atrophy type 3 to see if it is safe and helps improve their movement over time.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 2 Years and up
• Sex: All
• Sponsor: GeneCradle Inc (Industry-sponsored)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06421831 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of the GC101 gene therapy drug administered intrathecally to patients with spinal muscular atrophy type 3 (SMA 3). It is an open-label, dose-escalation study conducted across multiple centers in China. Participants will be monitored for short-term safety over 52 weeks and will enter a long-term follow-up phase lasting five years. Efficacy will be assessed at 12 months post-treatment using the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 2 years and older with a confirmed genetic diagnosis of SMA type 3 and specific functional motor scores.

Not a fit: Patients who have previously participated in gene therapy trials or have certain antibody levels may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve motor function in patients with spinal muscular atrophy type 3.

How similar studies have performed: Other studies have shown promise with gene therapy approaches for SMA, indicating potential for success with this novel treatment.

Eligibility criteria

Inclusion Criteria:

* ≥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;
* Patients or patient's legal guardian(s) must be able to understand the purpose and risks of the study and voluntarily provide signed and dated informed consent prior to any study-related procedures being performed.

Exclusion Criteria:

* 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;
* SMN2 copy numbers \>4；
* Patient who needs nasal or gastric tube feeding for eating;
* Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
* Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
* Severe contractures at screening that interfere with either the ability to attain/demonstrate functional measures or with the ability to receive intrathecal (IT) dosing;
* Patient who has other serious diseases, such as severe cardiovascular and cerebrovascular diseases, digestive system diseases, urinary system diseases, endocrine system diseases, hematological diseases, immune system diseases, nervous system diseases (including but not limited to epilepsy, meningitis, history of convulsions or seizures, cerebrospinal fluid circulation disorders), and mental illnesses, etc.;
* Patient with previous injuries (such as upper or lower limb fractures) or surgical operations that have not fully recovered or reached a stable state;
* Vaccination no longer than 2 weeks before treatment;
* Patient who has any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in the study.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Tiantan Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: GeneCradle, Inc China

Conditions Spinal Muscular Atrophy Type 3; SMA type 3