ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM)

Official title

Onasemnogene Abeparvovec: ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM)

Overview

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).

Detailed description

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.

Interventions

• Drug Onasemnogene Abeparvovec-brve
  administered once via lumbar puncture with systemic corticosteroid prophylaxis per label.

Primary outcome measures

• Change from baseline in HFMSE for independently ambulatory participants [Time frame: Baseline, 6, 12, 18 and 24 months]
• Change from baseline in RULM for non-ambulatory (including walkers with assistance) participants [Time frame: Baseline, 6, 12, 18 and 24 months]

Secondary outcome measures (12)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: up to 5 years]
• Modified SMA Functional Rating Scale (SMA-FRS) for independently ambulatory participants (≥ 18 years of age) and non-ambulatory particpants [Time frame: Baseline, 6, 12, 18 and 24 months and Years 3, 4, and 5]
• Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) for independently ambulatory participants (<18 years of age) [Time frame: Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5]
• Subgroup outcomes: Hammersmith Functional Motor Scale Expanded (HFMSE) [Time frame: Baseline, 6, 12, 18 and 24 months]
• Subgroup outcomes: Revised Upper Limb Module (RULM) [Time frame: Baseline, 6, 12, 18 and 24 months]
• Frequency of hospitalizations emergency department visits, outpatient visits, respiratory interventions and nutritional support interventions [Time frame: Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5]
• Duration of hospitalizations emergency department visits, outpatient visits, respiratory interventions and nutritional support interventions [Time frame: Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5]
• Cobb angle [Time frame: Baseline, up to 24 months]
• Daily hours of respiratory support (none, non-invasive ventilation, invasive ventilation) [Time frame: Baseline, up to 24 months]
• Joint-range limitation measured by goniometer [Time frame: Baseline, up to 24 months]
• Nutritional-support category (oral, gastrostomy feeds, total parenteral nutrition) [Time frame: Baseline, up to 24 months]
• 6-Minute Walk Test (6MWT) for ambulatory patients [Time frame: Baseline, Months 6, 12, 18, and 24]

Eligibility criteria

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:

• independently ambulatory child/adolescent 2 - <18 years; or
• independently ambulatory adult (≥ 18 years).
• 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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07448610 · COAV101B1US01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗