RECRUITINGPhase 1 / Phase 2INTERVENTIONAL
Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 1 Patients
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
About This Trial
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.
Who May Be Eligible (Plain English)
Who May Qualify:
- 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 willing to sign a consent form prior to any study-related procedures being performed.
Who Should NOT Join This Trial:
- 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 weakened immune system 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;
...See full criteria on ClinicalTrials.gov
Always talk to your doctor about whether this trial is right for you.
Original Eligibility Criteria
View original clinical language
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.
Treatments Being Tested
GENETIC
GC101
Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter
Locations (4)
Peking University， First Hospital, Department of Pediatrics
Beijing, China
Bayi Children's Hospital, Seventh Medical Center, PLA general hospital
Beijing, China
Shengjing Hospital of China Medical University
Shenyang, China
Children's Hospital of Soochow University
Suzhou, China