Spinal Muscular Atrophy
Conditions
Keywords
Type 1
Brief summary
The study will evaluate safety and efficacy of intrathecal delivery of GC101 gene therapy drug as a treatment of spinal muscular atrophy Type 1 (SMA 1) patients.
Detailed description
The purpose of this trial is to evaluate safety and efficacy of gene therapy drug GC101 in SMA 1 patients. Open-label, dose-escalation clinical trial of GC101 will be conducted in multiple centers in China. GC101 will be administrated intrathecally. Short-term safety will be evaluated in 52 weeks and enter long-term follow-up study of 5 years at will. Patients will be tested at baseline and followed up on various time points. The primary analysis for efficacy will be assessed when all patients reach 18 months of age on the motor milestone of sit unassisted for at least 10 seconds.
Interventions
GENETICGC101
Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter
Sponsors
GeneCradle Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Months to 6 Months
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | when patient reaches 18 months of age | Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests |
| Proportion of patients treated with GC101 who achieve motor milestone of sit unassisted for at least 10 seconds at 18 months of age | when patient reaches 18 months of age | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ability to thrive | when patient reaches 18 months of age | Ability to thrive is defined as the following at 18 months of age: does not receive nutrition through mechanical support or other non-oral method; maintains weight |
| Changes from baseline Children's hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score | when patient reaches 18 months of age | CHOP INTEND score ranges from 0 to 64 with higher scores indicating higher motor function |
| Proportion of event-free survival patients | when patient reaches 14 months of age | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients who achieve the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS) motor milestones | when patient reaches 18 months of age | WHO MGRS gross motor milestones and performance criteria included sitting without support for at least 10 seconds, Hands-and-knees crawling at least three in a row, standing with assistance for at least 10 seconds, walking with assistance at least five steps, standing alone for at least 10 seconds, and walking alone. |
Countries
China
Contacts
Primary ContactGeneCradle, Inc. China
Outcome results
None listed