Replacement Therapy Clinical Trial for Patients with Spinal Muscular Atrophy Type 1
Conditions
Sponsors
AveXis, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with SMA Type 1 as determined by the diagnosis of SMA based on gene mutation analysis with biallelic SMN1 mutations (deletion or point mutations) and one or two copies of SMN2 [inclusive of the known SMN2 gene modifier mutation (c.859G>C)] • Patients must be =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening - Pulse oximetry saturation must not decrease = four (4) percentage points between screening and dosing with confirmatory oximetry reading - Patients may be put on non-invasive ventilatory support for less than 12 hours per day at the discretion of their physician or trial staff. • Use or requirement of non-invasive ventilatory support for 12 or more hours daily in the two weeks prior to dosing. • Patient with signs of aspiration based on a swallowing test or whose weight-for-age falls below the 3rd percentile based on World Health Organization (WHO) Child Growth Standards [27] and is unwilling to use an alternative method to oral feeding. • Participation in recent SMA treatment clinical study (with the exception of observational cohort studies or non-interventional studies) or receipt of an investigational or commercial compound, product, or therapy administered with the intent to treat SMA (e.g., nusinersen, valproic acid) at any time prior to screening for this study. Oral ß-agonists must be discontinued at least 30 days before gene therapy dosing. Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable. • Patient < 35 weeks gestational age at time of birth.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Determine efficacy based on survival at 14 months of age. Survival is defined by the avoidance of combined endpoint of either (a) death or (b) permanent ventilation which is defined by tracheostomy or by the requirement of = 16 hours of respiratory assistance per day (via non invasive ventilatory support) for = 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation, so defined, is considered a surrogate for death.;Primary end point(s): • Proportion of symptomatic SMA Type 1 patients who are homozygous negative for SMN1 exon 7 and have two copies of SMN2 without the SMN2 genetic modifier that achieve the ability to sit without support for at least 10 seconds up to and including the 18 months of age trial visit. Sitting without support is defined by the World Health Organization Multicentre Growth Reference Trial (WHO MGRS), confirmed by video recording, as a patient who sits up straight with head erect for at least 10 seconds; child does not use arms or hands to balance body or support position. ;Main Objective: Determine efficacy by demonstrating achievement of developmental milestone of sitting without support up to 18 months of age as defined by WHO Motor Developmental Milestones ;Timepoint(s) of evaluation of this end point: 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Survival at 14 months of age amongst symptomatic SMA Type 1 patients who are homozygous negative for SMN1 exon 7 and have two copies of SMN2 without the SMN2 genetic modifier. Survival is defined by the avoidance of the combined endpoint of either (a) death or (b) permanent ventilation, which is defined by tracheostomy or by the requirement of = 16 hours of respiratory assistance per day (via non-invasive ventilatory support) for = 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation, so defined, is considered a surrogate for death. ;Timepoint(s) of evaluation of this end point: 14 months | — |
Countries
Belgium, France, Italy, Netherlands, Spain, Sweden, United Kingdom
Contacts
Public ContactSr. Clinical Trial Operations Mgr
AveXis, Inc.
Outcome results
None listed