Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies

Inclusion Criteria:

• Participants with SMA Type 1 as determined by diagnosis of SMA based on gene mutationanalysis with biallelic SMN1 mutations (deletion or point mutations) and one or 2copies of SMN2 [inclusive of the known SMN2 gene modifier mutation (c.859G>C)]
• Participants must be < 6 months (< 180 days) of age at the time of onasemnogeneabeparvovec-xioi infusion
• Participants must have a swallowing evaluation test performed prior to administrationof gene replacement therapy
• Up-to-date on childhood vaccinations as per local health authorities.
• Parent(s)/legal guardian(s) willing and able to complete the informed consent processand comply with trial procedures and visit schedule

Exclusion Criteria:

• Previous, planned or expected scoliosis repair surgery/procedure prior to 18 months ofage
• Use of invasive ventilatory support (tracheotomy with positive pressure) or pulseoximetry < 95% saturation at screening:

1. Pulse oximetry saturation must not decrease ≥ 4 percentage points betweenscreening and dosing with confirmatory oximetry reading
2. Participants may be put on non-invasive ventilatory support for less than 12hours per day at the discretion of their physician or trial staff

• Use or requirement of non-invasive ventilatory support for greater than or equal to 12hours daily in the two weeks prior to dosing
• Participant with signs of aspiration based on a swallowing test or whoseweight-for-age falls below the 3rd percentile based on World Health Organization (WHO)Child Growth Standards and unwilling to use an alternative method to oral feeding
• Active viral infection (includes human immunodeficiency virus [HIV] or positiveserology for hepatitis B, C, or E, or known Zika virus infection)
• Serious non-respiratory tract illness requiring systemic treatment and/orhospitalization within 2 weeks prior to screening
• Upper or lower respiratory infection requiring medical attention, medicalintervention, or increase in supportive care of any manner within 4 weeks prior toscreening
• Severe non-pulmonary/respiratory tract infection (eg, pyelonephritis, or meningitis)within 4 weeks before administration of gene replacement therapy or concomitantillness that, in the opinion of the Principal Investigator, creates unnecessary risksfor gene replacement such as:

1. Major renal or hepatic impairment
2. Known seizure disorder
3. Diabetes mellitus
4. Idiopathic hypocalcuria
5. Symptomatic cardiomyopathy

• Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids ortheir excipients, or human, animal biological raw materials (human transferrin, humaninsulin, trypsin derived from porcine spleen, bovine derived protein (FBS, bovinemilk-derived Benzonase, casamino acid, bovine pancreas), HEK 293 cells, Cosmic CalfSerum, HyQtase) used in manufacturing of onasemnogene abeparvovec-xioi product
• Concomitant use of any of the following: drugs for treatment of myopathy orneuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressivetherapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressivetherapy within 3 months prior to gene replacement therapy (e.g., corticosteroids,cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IV immunoglobulin,rituximab)
• Anti-AAV9 antibody titer > 1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. Should a potential participant demonstrate Anti-AAV9antibody titer > 1:50, he or she may receive retesting within 30 days of the screeningperiod and will be eligible to participate if the Anti-AAV9 antibody titer uponretesting is ≤ 1:50
• Clinically significant abnormal laboratory values (gamma-glutamyl transpeptidase [GGT], ALT, AST, total bilirubin > 2x the ULN, creatinine ≥ 1.0 mg/dL, hemoglobin [Hgb] < 8 or > 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to genereplacement therapy. Patients with an elevated bilirubin level that is unequivocallythe result of neonatal jaundice shall not be excluded
• Participation in recent SMA treatment clinical trial (with the exception ofobservational cohort studies or non-interventional studies) or receipt of aninvestigational or commercial compound, product or therapy administered with theintent to treat SMA (e.g., nusinersen, valproic acid) at any time prior to screeningfor this trial. Oral beta-agonists must be discontinued at least 30 days prior todosing. Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable and not a contraindication at any time priorto screening for this trial
• Expectation of major surgical procedures during the trial assessment period (e.g.,spinal surgery or tracheostomy)
• Parent(s)/legal guardian(s) unable or unwilling to comply with trial procedures orinability to travel for repeat visits
• Parent(s)/legal guardian(s) unwilling to keep trial results/observations confidentialor to refrain from posting confidential trial results/observations on social mediasites
• Parent(s)/legal guardian(s) refuses to sign consent form
• Participants < 35 weeks gestational age at time of birth