Gene therapy for treating spinal muscular atrophy Type 1

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 1 Patients

This study is testing a new gene therapy for babies with spinal muscular atrophy Type 1 to see if it helps them sit up on their own by 18 months old.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 0 Months to 6 Months
• Sex: All
• Sponsor: GeneCradle Inc (Industry-sponsored)
• Locations: 4 sites (Beijing and 3 other locations)
• Trial ID: NCT05824169 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 1 (SMA 1). 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 five years. The primary efficacy endpoint is the ability to sit unassisted for at least 10 seconds by the time patients reach 18 months of age.

Who should consider this trial

Good fit: Ideal candidates are infants six months of age or younger diagnosed with SMA Type 1 due to bi-allelic SMN1 mutations.

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

Why it matters

Potential benefit: If successful, this gene therapy could significantly improve motor function and quality of life for infants with SMA Type 1.

How similar studies have performed: While gene therapy approaches for SMA have shown promise, this specific trial with GC101 represents a novel intervention.

Eligibility criteria

Inclusion Criteria:

* Six months of age and younger on day of vector infusion with Type 1 SAM 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 SMN2;
  * Onset of disease before 6 months of age
* 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 a previous gene therapy research trials;
* Patient who has received Nusinersen and Risdiplam treatment;
* Patient who has AAV9 neutralizing antibody titer ≥1:200;
* Patient who requires non-invasive ventilatory support averaging≥16 hours/day;
* Patient with a point mutation in SMN2 (c.859G\>C);
* Patient who requires non-invasive ventilatory support averaging≥16 hours/day at screening;
* Patient who 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 \<183x10\^9/L or 614x10\^9/L;
* 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 3 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)
• Shengjing Hospital of China Medical University — Shenyang, China (Recruiting)
• Children's Hospital of Soochow University — Suzhou, China (Recruiting)

Study contacts

• Study coordinator: GeneCradle, Inc. China

Conditions Spinal Muscular Atrophy; Type 1