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)

NCT07448610 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: COAV101B1US01
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Spinal Muscular Atrophy

Keywords

Spinal muscular atrophy; SMA; onasemnogene abeparvovec-brve; intrathecal gene therapy; ITVISMA®; real-world evidence; sponsor-funded; real-world pragmatic trial;; motor function; safety.

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, 6, 12, 18 and 24 months

• 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.

  Baseline, 6, 12, 18 and 24 months

Secondary Outcomes (12)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  up to 5 years

• Modified SMA Functional Rating Scale (SMA-FRS) for independently ambulatory participants (≥ 18 years of age) and non-ambulatory particpants

  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)

  Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5

• Subgroup outcomes: Hammersmith Functional Motor Scale Expanded (HFMSE)

  Baseline, 6, 12, 18 and 24 months

• Subgroup outcomes: Revised Upper Limb Module (RULM)

  Baseline, 6, 12, 18 and 24 months

Study Arms (1)

Onasemnogene Abeparvovec-brve

EXPERIMENTAL

Participants with spinal muscular atrophy, including: * independently ambulatory children/adolescents (≥ 2 years to \< 18 years); * independently ambulatory adults (≥ 18 years); * Non-ambulatory adults (≥ 18 years)

Drug: Onasemnogene Abeparvovec-brve

Interventions

Onasemnogene Abeparvovec-brve DRUG

administered once via lumbar puncture with systemic corticosteroid prophylaxis per label.

Also known as: (ITVISMA®)

Onasemnogene Abeparvovec-brve

Eligibility Criteria

• Age: 2 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 4, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 3, 2032
• Study Completion (Estimated): June 30, 2032
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share