Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1
Condition: Spinal Muscular Atrophy 1
MeSH terms: Muscular Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Atrophy
Intervention: AVXS-101
Intervention description: Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Maximum age: 6 Months
Healthy volunteers: No
Keywords: Gene Transfer; Gene Therapy; Adeno-associated virus; Survival Motor Neuron; SMN; AAV9

Summary:

      The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of
      AVXS-101 as a treatment of spinal muscular atrophy Type 1 (SMN1).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Six or nine months of age and younger (depending on cohort) on day of vector infusion
             with Type 1 SMA as defined by the following features:

               -  Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations
                  (deletion or point mutations) and 2 copies of SMN2.

               -  Onset of disease at birth up to 6 months of age.

               -  Hypotonia by clinical evaluation with delay in motor skills, poor head control,
                  round shoulder posture and hypermobility of joints.

        Exclusion Criteria:

          -  Active viral infection (includes HIV or serology positive for hepatitis B or C)

          -  Use of invasive ventilatory support (tracheotomy with positive pressure)* or pulse
             oximetry <95% saturation.

          -  Patients may be put on non-invasive ventilator support (BiPAP) for less than 16 hours
             a day at the discretion of their physician or research staff.

          -  Concomitant illness that in the opinion of the PI creates unnecessary risks for gene
             transfer

          -  Concomitant use of any of the following drugs: drugs for treatment of myopathy or
             neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive
             therapy or immunosuppressive therapy within 3 months of starting the trial (e.g.
             corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous
             immunoglobulin, rituximab)

          -  Patients with Anti-AAV9 antibody titers >1:50 as determined by ELISA binding
             immunoassay.

          -  Abnormal laboratory values considered clinically significant (GGT > 3XULN, bilirubin ≥
             3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 20,000 per cmm)
             Participation in a recent SMA treatment clinical trial that in the opinion of the PI
             creates unnecessary risks for gene transfer.

          -  Family does not want to disclose patient's study participation with primary care
             physician and other medical providers.

          -  Patient with signs of aspiration based on a swallowing test and unwilling to use an
             alternative method to oral feeding.

          -  Patients with a single base substitution in SMN2 (c.859G>C in exon 7) will be excluded
             based on predicted mild phenotype.