Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 1 Patients

Plain-language summary

This Phase 1/2 study evaluates the safety and efficacy of intrathecal delivery of the GC101 gene therapy drug in patients with spinal muscular atrophy Type 1. Eligible infants are six months of age or younger on the day of vector infusion, with a genetically confirmed diagnosis based on bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2, and disease onset before 6 months. The trial is currently recruiting.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

PHASE1/PHASE2

Status

Recruiting

Sponsor

GeneCradle Inc

Intervention

GC101

Start date

2/25/2023

Estimated completion

12/1/2026

Countries

China

Related genes

Locations

• Beijing, China
• Beijing, China
• Shenyang, China
• Suzhou, China

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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.