Pre-Symptomatic Study of Intravenous AVXS-101 in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2 (SPR1NT)
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|ClinicalTrials.gov Identifier: NCT03505099|
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : February 27, 2019
|Condition or disease||Intervention/treatment||Phase|
|Spinal Muscular Atrophy||Biological: AVXS-101||Phase 3|
Phase 3, open-label, single-arm study of a single, one-time dose of AVXS-101 (gene replacement therapy) in patients with spinal muscular atrophy who meet enrollment criteria and are genetically defined by bi-allelic deletion of survival motor neuron 1 gene (SMN1) with 2 or 3 copies of survival motor neuron 2 gene (SMN2). Patients with SMN1 point mutations or the SMN2 gene modifier mutation (c.859G>C) may enroll but will not be included in the efficacy analysis sets.
The study includes a screening period, a gene replacement therapy period, and a follow-up period. During the screening period (Days -30 to -2), patients whose parent(s)/legal guardian(s) provide informed consent will undergo screening procedures to determine eligibility for study enrollment. Patients who meet the entry criteria will enter the in-patient gene replacement therapy period (Day -1 to Day 2). On Day -1, patients will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, patients will receive a single, one-time intravenous (IV) infusion of AVXS-101, and will undergo in-patient safety monitoring for a minimum of 24 hours post infusion. Patients may be discharged 24 hours after the infusion, based on Investigator judgment. During the outpatient follow-up period (Days 3 to End of Study at 18 or 24 of age, dependent upon respective SMN2 copy number), patients will return at regularly scheduled intervals for efficacy and safety assessments until the End of Study when the patient reaches 18 months of age (SMN2 = 2) or 24 months of age (SMN2 = 3). After the End of Study visit, eligible patients will be asked to rollover into a long-term follow up study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open-label, single arm|
|Masking:||None (Open Label)|
|Official Title:||A Global Study of a Single, One-Time Dose of AVXS-101 Delivered to Infants With Genetically Diagnosed and Pre-symptomatic Spinal Muscular Atrophy With Multiple Copies of SMN2|
|Actual Study Start Date :||April 10, 2018|
|Estimated Primary Completion Date :||October 2020|
|Estimated Study Completion Date :||June 2023|
One-time intravenous infusion of AVXS-101 at 1.1 X 10^14 vg/kg
A non-replicating recombinant AAV9 containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription.
- Percentage of participants achieving functional independent sitting for at least 30 seconds at any visit [ Time Frame: 18 months ]Participants with bi-allelic SMN1 deletions and 2 copies of SMN2
- Percentage of participants achieving the ability to stand without support for at least 3 seconds at any visit [ Time Frame: 24 months ]Participants with bi-allelic SMN1 deletions and 3 copies of SMN2
- Percentage of participants surviving without permanent ventilation in the absence of acute illness and perioperatively [ Time Frame: 14 months ]Participants with bi-allelic SMN1 deletions and 2 copies of SMN2
- Percentage of participants achieving the ability to maintain weight at or above the 3rd percentile without non-oral/mechanical feeding support at any visit [ Time Frame: 18 months ]Participants with bi-allelic SMN1 deletions and 2 copies of SMN2
- Percentage of participants demonstrating the ability to walk alone at any visit [ Time Frame: 24 months ]Participants with bi-allelic SMN1 deletions and 3 copies of SMN2. Ability to walk alone is defined as the ability to take at least 5 steps independently displaying coordination and balance.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03505099
|Contact: AveXis MedInfoemail@example.com|
Show 24 Study Locations
|Study Chair:||Doug Feltner, MD||AveXis, Inc.|