Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients with Spinal Muscular Atrophy Type 1 with One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusio
- Conditions
- 10010335Spinal muscular atrophy type 1 / Reduction of nerve cells in the spinal cord resulting in muscle paralysis
- Registration Number
- NL-OMON48542
- Lead Sponsor
- AveXis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 5
1. Patients with SMA Type 1 as determined by the diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and one or two copies of SMN2 [inclusive of the known SMN2 gene modifier mutation (c.859G>C)]
2. Patients must be < 6 months (< 180 days) of age at the time of AVXS 101 infusion.
3. Patients must have a swallowing evaluation test performed prior to administration of gene replacement therapy.
1. Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening
a. Pulse oximetry saturation must not decrease * four ( 4) percentage points between screening and dosing with confirmatory oximetry reading
b. 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.;2. Use or requirement of non-invasive ventilatory support for *12 or more hours daily in the two 2 weeks prior to dosing.;3 Patient with signs of aspiration based on a swallowing test or whose weight-for-age is below the 3rd percentile based on World Health Organization (WHO) Child Growth Standards and is unwilling to use an alternative method to oral feeding.;4. Participation in recent SMA treatment clinical trial (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 (eg, nusinersen, valproic acid,) at any time prior to screening for this trial. Oral *-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.;5. Patient < 35 weeks gestational age at time of birth
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Proportion of symptomatic SMA Type 1 patients who are homozygous negative for<br /><br>SMN1 exon 7 and have two copies of SMN2 without the SMN2 genetic modifier that<br /><br>achieve the ability to sit without support for at least 10 seconds up to and<br /><br>including the 18 month trial visit. Sitting without supportIt is defined by<br /><br>the World Health Organization Multicentre Growth Reference Trial (WHO MGRS),<br /><br>confirmed by video recording, as a patient who sits up straight with head erect<br /><br>for at least 10 seconds; child does not use arms or hands to balance body or<br /><br>support position.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Survival at 14 months of age amongst symptomatic SMA Type 1 patients who are<br /><br>homozygous negative for SMN1 exon 7 and have two copies of SMN2 without the<br /><br>SMN2 genetic modifier. Survival is defined by the avoidance of the combined<br /><br>endpoint of either (a) death or (b) permanent ventilation, which is defined by<br /><br>tracheostomy or by the requirement of * 16 hours of respiratory assistance per<br /><br>day (via non invasive ventilatory support) for * 14 consecutive days in the<br /><br>absence of an acute reversible illness, excluding perioperative ventilation.<br /><br>Permanent ventilation, so defined, is considered a surrogate for death.</p><br>