The primary purpose is to address critical evidence in the treatment landscape for Spinal Muscular Atrophy (SMA), specifically focusing on the intrathecal formulation of onasemnogene abeparvovec-brve (ITVISMA®). U.S. Pragmatic Multicenter Study (STREAM).

STREAM is a prospective, multicentre cohort study that will follow U.S. participants with genetically confirmed SMA who receive a single, intrathecal dose of onasemnogene abeparvovec-brve. All eligible participants are enrolled prior to therapeutic injection. No randomisation, blinding, or placebo control is employed; instead, each participant acts as his or her own baseline comparator. This study will use an exploratory external cohort of patients matched by age, clinical characteristics, treatment history and availability of at least 1 year of pre-treatment medical history. This patient cohort will be based on a database of retrospectively collected electronic medical records data and will be used descriptively to contextualize study outcomes. Bias is minimised through pre-specified endpoints, uniform rater training on motor-function scales, and a detailed statistical analysis plan that stipulates handling of missing data and intercurrent events in advance.

Key Inclusion Criteria:

A participant will be enrolled in STREAM only if all the following conditions are met:

• The participant has a genetically confirmed diagnosis of SMA (biallelic SMN1 deletion or mutation).

• He or she is ≥ 2 years of age on the day of the intrathecal injection.

• The treating Investigator intends to administer within the current episode of care, a single dose of ITVISMA® (1.2 × 10¹⁴ vg) in routine U.S. practice after written informed consent obtained.

• One of the following functional categories applies at screening:

  1. independently ambulatory child/adolescent 2 - <18 years; or
  2. independently ambulatory adult (≥ 18 years).
  3. non-ambulatory (includes walkers with assistance) adult > 18 years with entry level RULM at baseline

• At least 1 year of pre-treatment medical history, including motor-function documentation, can be retrieved from the site electronic record.

Key Exclusion Criteria:

A participant will be excluded if any of the following conditions apply:

• Contraindication for lumbar puncture as determined by the investigator (e.g., spinal anatomy that precludes safe lumbar puncture)
• An uncontrolled acute illness, active infection, febrile illness or acute medical condition, within 30 days prior to dosing
• Inability to tolerate corticosteroids administered by mouth or gastrostomy tube
• Current participation in another interventional clinical trial that would interfere with the objectives or endpoints of STREAM. Note: participation in observational cohort studies or non-interventional studies in which the participant does not receive treatment or undergo procedures which may compromise this study data integrity may be allowed following Sponsor approval
• Planned relocation or any circumstance that is likely to prevent completion of the minimum 12-month follow-up.

Other protocol inclusion, exclusion criteria may apply.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.