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)

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)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Muscular Atrophy
• Intervention / Treatment: Drug: Onasemnogene Abeparvovec-brve

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Onasemnogene Abeparvovec-brve; 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; administered once via lumbar puncture with systemic corticosteroid prophylaxis per label.; Other Names: (ITVISMA®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 5 years
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.	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)	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.	Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5
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.	Baseline, 6, 12, 18 and 24 months
Subgroup outcomes: Revised Upper Limb Module (RULM)	Effectiveness assessment across predefined participant groups based on relevant clinical and demographic factors, as specified in the protocol. The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in independent ambulatory and non-independent ambulatory individuals with SMA. Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.	Baseline, 6, 12, 18 and 24 months
Frequency of hospitalizations emergency department visits, outpatient visits, respiratory interventions and nutritional support interventions	Assessment of SMA-related healthcare-resource utilisation.	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	Assessment of SMA-related healthcare-resource utilisation.	Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5
Cobb angle	Assessment of scoliosis progression as a disease-progression marker.	Baseline, up to 24 months
Daily hours of respiratory support (none, non-invasive ventilation, invasive ventilation)	Assessment of respiratory function as a disease-progression marker.	Baseline, up to 24 months
Joint-range limitation measured by goniometer	Assessment of evolution of joint contractures as a disease-progression marker.	Baseline, up to 24 months
Nutritional-support category (oral, gastrostomy feeds, total parenteral nutrition)	Assessment of nutrition status as a disease-progression marker.	Baseline, up to 24 months
6-Minute Walk Test (6MWT) for ambulatory patients	To assess disease-progression markers. 6MWT: distance in metres; greater distance indicates better ambulatory capacity.	Baseline, Months 6, 12, 18, and 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 3, 2032
• Study Completion (Estimated): June 30, 2032

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: SMA; motor function; Spinal muscular atrophy; real-world evidence; safety.; onasemnogene abeparvovec-brve; intrathecal gene therapy; ITVISMA®; sponsor-funded; real-world pragmatic trial
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal
• Other Study ID Numbers: COAV101B1US01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No