Spinal Muscular Atrophy
Conditions
Sponsors
Novartis Gene Therapies, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients: •Age =6 weeks (=42 days) at time of dose •Ability to tolerate thin liquids as demonstrated through a formal bedside swallowing test •Compound muscle action potential (CMAP) =2 mV at Baseline •Gestational age of 35 to 42 weeks •Genetic diagnosis as described below, obtained from an acceptable newborn or pre-natal screening test method Patients with 2 copies of SMN2 •Patients with pre-symptomatic SMA Type 1 as determined by the following features: •Bi-allelic deletion of SMN1 •2 copies of SMN2 Patients with 3 copies of SMN2 •Patients with pre-symptomatic SMA Type 2 as determined by the following features: •Bi-allelic deletion of SMN1 •3 copies of SMN2 Are the trial subjects under 18? yes Number of subjects for this age range: 29 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Weight at screening visit 2 x the ULN, creatinine = 1.0 mg/dL, haemoglobin [Hgb] 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy. Patients with an elevated bilirubin level that is unequivocally the result of neonatal jaundice shall not be excluded. •Patients with any other clinically significant abnormalities in hematology or clinical chemistry parameters as determined by the investigator or medical monitor •Treatment with an investigational or commercial product, including nusinersen, given for the treatment of SMA. This includes any history of gene therapy, prior antisense oligonucleotide treatment, or cell transplantation. •Patients whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards •Serious non respiratory tract illness requiring systemic treatment and/or hospitalization within 2 weeks prior to screening •Upper or lower respiratory infection requiring medical attention, medical intervention, or increase in supportive care of any manner within 4 weeks prior to dosing •Previous, planned or expected major surgical procedure including scoliosis repair surgery/procedure during the study assessment period •Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive therapy within 4 weeks prior to gene replacement therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IV immunoglobulin, rituximab) •Anti AAV9 antibody titer >1:50 as determined by Enzyme linked Immunosorbent Assay (ELISA) binding immunoassay
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety • Evaluate the safety of AVXS-101 through incidence of adverse events (AEs) and/or serious adverse events (SAEs) •Evaluate the safety of AVXS-101 based on the change from baseline in clinical laboratory parameters Efficacy objectives will be assessed independently for each cohort. Efficacy for patients with bi-allelic SMN1 deletions and 2 copies of SMN2: •Assess the efficacy of AVXS-101 by demonstrating functional independent sitting for at least 30 seconds as defined by Bayley Scales of Infant and Toddler Development© Version 3 (BSIDv03) Gross Motor Subset Item #26 at any visit up to 18 months of age Efficacy for patients with 3 copies of SMN2: •Assess the efficacy of AVXS-101 based on the proportion of patients achieving the ability to stand without support for at least three seconds as defined by Bayley Scales of Infant and Toddler Development© Version 3 (BSIDv03) Gross Motor Subset Item #40 at any visit up to 24 months of age;Secondary Objective: Efficacy for patients with 2 copies of SMN2: •Determine the efficacy of AVXS-101 based on survival, defined as avoidance of death or the requirement of permanent ventilation in the absence of acute illness or perioperatively as assessed at 14 months of age •Assess efficacy of AVXS-101 by demonstrating the ability to maintain weight at or above the third percentile without need for non-oral/mechanical feeding support at any visit up to 18 months of age Efficacy for patients with 3 copies of SMN2: •Assess the efficacy of AVXS-101 by demonstrating the ability to walk alone defined as the ability to take at least five steps independently displaying coordination and balance, as defined by BSIDv03 Gross Motor Subtest Item #43, at any visit up to 24 months of age;Primary end point(s): Criteria for Evaluation: Safety: Primary: •Incidence of adverse events (AEs) and/or serious adverse events (SAEs) •Change from baseline in clinical laboratory parameters Efficacy objectives will be assessed independently | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Patients with 2 copies of SMN2: •Proportion of patients that have survived and have not required permanent ventilation in the absence of acute illness or perioperatively assessed at 14 months of age •Proportion of patients that have achieved the ability to maintain weight at or above the third percentile without need for non-oral/mechanical feeding support at any visit up to 18 months of age Patients with 3 copies of SMN2: •Proportion of patients demonstrating the ability to walk alone defined as the ability to take at least five steps independently displaying coordination and balance at any visit up to 24 months of age;Timepoint(s) of evaluation of this end point: Patients with 2 copies of SMN2: •Proportion of patients that have survived and have not required permanent ventilation assessed at 14 months of age •Proportion of patients that have achieved the ability to maintain weight at or above the third percentile without need for non-oral/mechanical feeding support at any visit up to 18 months of age Patients with 3 copies of SMN2: •24 months of age | — |
Countries
Australia, Belgium, Canada, Germany, Israel, Italy, Japan, Korea, Democratic People's Republic of, Netherlands, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactSr. Global Trial Operations Manager
Novartis Gene Therapies, Inc.
Outcome results
None listed