Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
Condition: Spinal Muscular Atrophy Type I
MeSH terms: Muscular Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Atrophy
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a Phase 3, open-label, single-arm, single-dose, trial of onasemnogene
      abeparvovec-xioi (gene replacement therapy) in participants with spinal muscular atrophy
      (SMA) Type 1 and who are genetically defined by a biallelic pathogenic mutation of the
      survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene
      (SMN2). The primary objective of the study is to evaluate the efficacy of onasemnogene
      abeparvovec-xioi by assessing the proportion of symptomatic SMA Type 1 participants who
      achieve the ability to sit unaided for at least 10 seconds up to and including the 18 months
      of age trial visit. At least 6 participants aged < 6 months (< 180 days) at the time of gene
      replacement therapy (Day 1) will be enrolled.
    

Detailed description: 
      This is a Phase 3, open-label, single-arm, single-dose trial of onasemnogene abeparvovec-xioi
      (gene replacement therapy) in participants with SMA Type 1 with one or 2 copies of SMN2. At
      least 6 participants < 6 months (< 180 days) of age at the time of gene replacement therapy
      (Day 1) will be enrolled.

      The trial includes 3 trial periods: screening, gene replacement therapy, and follow-up.
      During the screening period (Days -30 to -2), participants whose parent(s)/legal guardian(s)
      provide informed consent will undergo screening procedures to determine eligibility for trial
      enrollment. participants who meet the entry criteria will enter the in-patient gene
      replacement therapy period (Day -1 to Day 3). On Day -1, participants will be admitted to the
      hospital for pre-treatment baseline procedures. On Day 1, participants will receive a
      one-time intravenous (IV) infusion of the equivalent of onasemnogene abeparvovec-xioi cohort
      2 dose received in the AVXS-101-CL-101 trial over approximately 60 minutes and will undergo
      in-patient safety monitoring over the next 48 hours. Participants may be discharged 48 hours
      after gene replacement therapy, based on Investigator judgment. During the outpatient
      follow-up period (Days 4 to End of Trial at 18 months of age), participants will return at
      regularly scheduled intervals for efficacy and safety assessments until the participant
      reaches 18 months of age.
    

Intervention name(s): Onasemnogene Abeparvovec-xioi
Intervention type(s): Biological
Intervention description(s): Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the human survival motor neuron (SMN) gene under the control of the cytomegalovirus (CMV) enhancer/chicken β-actin-hybrid promoter (CB). Onasemnogene abeparvovec-xioi will be administered as a one-time intravenous infusion over approximately 60 minutes. Dosage will be determined by the participants weight.
Other intervention name(s): Zolgensma
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Spinal Muscular Atrophy; SMN2; Onasemnogene Abeparvovec-xioi; Gene replacement therapy