Gene therapy for treating spinal muscular atrophy Type 2

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 2 Patients

This study is testing a new gene therapy for people with spinal muscular atrophy Type 2 to see if it is safe and helps improve their movement over time.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 6 Months to 60 Months
• Sex: All
• Sponsor: GeneCradle Inc (Industry-sponsored)
• Locations: 5 sites (Beijing and 4 other locations)
• Trial ID: NCT05901987 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of the GC101 gene therapy drug delivered intrathecally to patients with spinal muscular atrophy Type 2 (SMA 2). It is an open-label, dose-escalation trial 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 5 years. Efficacy will be primarily assessed by measuring motor milestones and changes in HFMSE scores at various time points.

Who should consider this trial

Good fit: Ideal candidates are children aged 6 to 60 months diagnosed with SMA Type 2 who can sit independently but cannot stand or walk unassisted.

Not a fit: Patients who have previously participated in gene therapy trials or have received certain other SMA treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve motor function in children with SMA Type 2.

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:

* Between 6 months and 60 months of age on day of signing informed consent form;
* Patient with SMA Type 2 as defined by the following features:

  * Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN
  * Onset of disease between 6 and 18 months of age
* Patient who can sit alone but never be able to stand or walk alone ;
* The 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 received Nusinersen within 4 months and Risdiplam within 15 days before treatment;
* Patient who has AAV9 neutralizing antibody titer ≥1:200;
* Patient with a point mutation in SMN2 (c.859G\>C);
* Patient who requires non-invasive ventilatory support averaging≥12 hours/day at screening, or use invasive ventilatory support or pulse oximetry \< 95% saturation while awake and calm at screening;
* Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
* Abnormal laboratory values considered clinically significant, including gamma-glutamyl transferase(GGT), Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin \> 3x upper limit of normal (ULN), Hemoglobin (Hgb)\< 110 or \>150 g/L, platelet \<lower limit of normal (LLN);Class IV patient based on Modified Ross Heart Failure Classification for Children;
* Patient with a history of glucocorticoid allergy;
* Contraindication that would interfere with the lumbar puncture procedures;
* Presence of an untreated active infection requiring systemic antiviral therapy at any time during the screening period;
* Vaccination less than 2 weeks before infusion of vector;
* Patient who has any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.

Note: Other protocol defined inclusion/exclusion criteria may apply.

Where this trial is running

Beijing and 4 other locations

• Peking University， First Hospital, Department of Pediatrics — Beijing, China (Recruiting)
• Bayi Children's Hospital, Seventh Medical Center, PLA general hospital — Beijing, China (Recruiting)
• West China Second University Hospital, Sichuan University — Chengdu, China (Not_yet_recruiting)
• Children's Hospital of Chongqing Medical University — Chongqing, China (Not_yet_recruiting)
• Tongji Medical college of Huazhong University of Science&Technology, Affiliated Children's Hospital — Wuhan, China (Not_yet_recruiting)

Study contacts

• Study coordinator: GeneCradle, Inc. China

Conditions SMA II