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).
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.
independently ambulatory child/adolescent 2 - <18 years; or
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
Single group
Onasemnogene Abeparvovec-brve
Drugadministered once via lumbar puncture with systemic corticosteroid prophylaxis per label.
Change from baseline in HFMSE for independently ambulatory participants
The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
Change from baseline in RULM for non-ambulatory (including walkers with assistance) participants
The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in independent ambulatory and non-ambulatory (including walkers with assistance) individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of AEs and SAEs, including changes in laboratory tests and procedure-related events qualifying and reported as AEs.
Modified SMA Functional Rating Scale (SMA-FRS) for independently ambulatory participants (≥ 18 years of age) and non-ambulatory particpants
Modified Spinal Muscular Atrophy Functional Rating Scale (SMAFRS): Ten items address questions related to eating, upper extremity dressing, lower extremity dressing, grooming, bathing, toileting, turning in bed and adjusting bed clothes, transfers, walking, and climbing stairs. This outcome measure includes effectiveness assessment across predefined participant groups based on relevant clinical and demographic factors, as specified in the protocol.
Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) for independently ambulatory participants (<18 years of age)
The Assessment of Caregiver Experience with Neuromuscular Disease (ACEND): quantifies caregivers' perceptions of function and quality of life pertaining to time, finance and emotion. The ACEND was developed and validated to specifically assess caregiver impact experienced by raising children severely affected by neuromuscular diseases. While specifically developed for application to caregivers of patients undergoing orthopedic surgery, it has application to those with SMA. This outcome measure includes effectiveness assessment across predefined participant groups based on relevant clinical and demographic factors, as specified in the protocol.
Subgroup outcomes: Hammersmith Functional Motor Scale Expanded (HFMSE)
Effectiveness assessment across predefined participant groups based on relevant clinical and demographic factors, as specified in the protocol. The HFMSE is a validated SMA specific assessment to give objective information on motor ability and clinical progression. Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
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