Gene Replacement Therapy Clinical Trial for Participants With Spinal Muscular Atrophy Type 1

Exclusion Criteria

• •Previous, planned or expected scoliosis repair surgery/procedure during the study assessment period
• •Pulse oximetry \< 96% saturation at screening while the participant is awake or asleep without any supplemental oxygen or respiratory support, or for altitudes \> 1000 m, oxygen saturation \< 92% awake or asleep without any supplemental oxygen or respiratory support Pulse oximetry saturation may decrease to \< 96% after screening provided that the saturation does not decrease by ≥ 4 percentage points
• •Tracheostomy or current use or requirement of non-invasive ventilatory support averaging ≥ 6 hours daily over the 7 days prior to the screening visit; or ≥ 6 hours/day on average during the screening period or requiring ventilatory support while awake over the 7 days prior to screening or at any point during the screening period prior to dosing
• •Participants with signs of aspiration/inability to tolerate non-thickened- liquids based on a formal swallowing test performed as part of screening. Participants with a gastrostomy tube who pass the swallowing test will be allowed to enroll in the study
• •Participants whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards
• •Active viral infection (includes human immunodeficiency virus \[HIV\] or positive serology for hepatitis B or C, or Zika virus)
• •Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization within 2 weeks prior to screening
• •Upper or lower respiratory infection requiring medical attention, medical intervention, or increase in supportive care of any manner within 4 weeks prior to screening
• •Severe non-pulmonary/respiratory tract infection within 4 weeks before administration of gene replacement therapy or concomitant illness that creates unnecessary risks for gene replacement therapy such as: a. Major renal or hepatic impairment b. Known seizure disorder c. Diabetes mellitus d. Idiopathic hypocalcuria e. Symptomatic cardiomyopathy
• •Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
• •Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive therapy within 3 months prior to gene replacement therapy
• •Anti-adeno-associated virus serotype 9 (AAV9) antibody titer \> 1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. Should a potential participant demonstrate Anti-AAV9 antibody titer \> 1:50, he or she may receive retesting within 30 days of the screening period and will be eligible to participate if the Anti-AAV9 antibody titer upon retesting is ≤ 1:50
• •Clinically significant abnormal laboratory values (gamma glutamyl- transpeptidase \[GGT\], ALT, and AST \> 3 × ULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.0 mg/dL, hemoglobin \[Hgb\] \< 8 or \> 18 g/dL; white blood cell \[WBC\] \> 20,000 per cmm) prior to gene replacement therapy
• •Participation in recent SMA treatment clinical study (with the exception of observational Cohort studies or non-interventional studies) or receipt of an investigational or commercial compound, product, or therapy administered with the intent to treat SMA at any time prior to screening for this study. Oral β-agonists must be discontinued at least 30 days before gene therapy dosing. Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable and not a contraindication at any time prior to screening for this study
• •Expectation of major surgical procedures during the study assessment period
• •Parent(s)/legal guardian(s) unable or unwilling to comply with study procedures or inability to travel for repeat visits
• •Parent(s)/legal guardian(s) unwilling to keep study results/observations confidential or to refrain from posting confidential study results/observations on social media sites
• •Parent(s)/legal guardian(s) refuses to sign consent form
• •Gestational age at birth \< 35 weeks (245 days)