Overview
GB221 is a gene therapy that delivers a working SMN1 gene to the motor neurons of people with spinal muscular atrophy (SMA) Type 1. This study will evaluate the safety, tolerability and efficacy of GB221 in two groups:
- participants aged from 2 weeks to younger than 12 months presenting with symptoms of SMA Type 1 who have never received a treatment OR are receiving the drug risdiplam
- participants aged from 2 weeks to younger than 5 months who are at risk of developing SMA Type 1 (presymptomatic) and have never received treatment OR are receiving the drug risdiplam.
Eligibility
Inclusion Criteria:
- Symptomatic Participants
- Diagnosis of SMA Type 1 based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and up to 3 copies of SMN2
- Participants must be 2 weeks to \< 12 months of age at the time of dosing with disease onset of during the first 6 months of life.
- Presymptomatic Participants
- At risk of SMA Type 1 based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and up to 2 copies of SMN2
- Participants must be 2 weeks to \< 5 months (\< 150 days) of age at the time of dosing.
Exclusion Criteria:
- Any suspected or confirmed active viral infection at screening baseline (including HIV, Hepatitis B or C, or human T Cell lymphotropic viruses \[HTLV\])
- History of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry \<95% saturation.
- Ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
- Participation in a recent SMA treatment clinical trial that, in the opinion of the Investigator, creates unnecessary risks for gene transfer.
- Prior history of gene therapy for any indication, hematopoietic transplant or solid organ transplant
- Subjects with severe scoliosis
- Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients.
