Spinal Muscular AtrophyPhase 4NCT07448610
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)
A Phase 4 study testing Onasemnogene Abeparvovec-brve in people with Spinal Muscular Atrophy, run by Novartis Pharmaceuticals at 6 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 to 100 years
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- Onasemnogene Abeparvovec-brve
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 6 sitesUnited States
- Study dates
- 27 Aug 2026to 30 Jun 2032
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Novartis Pharmaceuticals contact
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
Boston Childrens Hospital
Boston, Massachusetts, 02215
Maggie Allen, (617) 919-3554, Maggie.Allen@childrens.harvard.edu
Leslie Hayes
- Recruiting
Ohio State University Medical Center
Columbus, Ohio, 43210
Georgia (Gia) Cinkay, (614) 366-9050, Georgia.cinkay@osumc.edu
Bakri Elsheikh
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 208833
Buffy Gofforth, (501) 364-1591
Aravindhan Veerapandiyan
- Recruiting
Columbia University Medical Center
New York, New York, 10032
Kimberly Berry, 212-342-3038, kb2996@cumc.columbia.edu
Claudia Chiriboga
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 209277
Amanda (Mandy) Hicks, (267) 496-3772, amanda.hicks@pennmedicine.upenn.edu
Lauren Elman
- Recruiting
Stanford Hospital
Stanford, California, 94305-5235
(650) 725-4341, NeuromuscularResearch@stanford.edu
John W Day
About this study
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)
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).
Read the 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.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- Onasemnogene Abeparvovec-brve
- Keywords
- Spinal muscular atrophy, SMA, onasemnogene abeparvovec-brve, intrathecal gene therapy, ITVISMA®, real-world evidence, sponsor-funded, real-world pragmatic trial;, motor function, safety.
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Onasemnogene Abeparvovec-brveDrug
Also called (ITVISMA®)
administered once via lumbar puncture with systemic corticosteroid prophylaxis per label.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Onasemnogene Abeparvovec-brve |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline, 6, 12, 18 and 24 months
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Months 6, 12, 18, 24, and Years 3, 4, and 5
Cobb angle
Assessment of scoliosis progression as a disease-progression marker.
Measured: 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.
Measured: Baseline, up to 24 months
Joint-range limitation measured by goniometer
Assessment of evolution of joint contractures as a disease-progression marker.
Measured: Baseline, up to 24 months
Nutritional-support category (oral, gastrostomy feeds, total parenteral nutrition)
Assessment of nutrition status as a disease-progression marker.
Measured: 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.
Measured: Baseline, Months 6, 12, 18, and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2026
- Study start27 Aug 2026
- Primary completion3 May 2032 (estimated)
- Study completion30 Jun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07448610
- Sponsor's protocol ID
- COAV101B1US01
- Status last verified
- Oct 2026
- First submitted
- 26 Feb 2026
- Last updated
- 29 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT07448610
- Acronym / sponsor ID
- COAV101B1US01
- 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;
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 27 Aug 2026 (actual)
- Primary completion
- 3 May 2032 (estimated)
- Study completion
- 30 Jun 2032 (estimated)
- First posted
- 4 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Onasemnogene Abeparvovec-brve | Experimental | Drug: Onasemnogene Abeparvovec-brveParticipants with spinal muscular atrophy, including: * independently ambulatory children/adolescents (≥ 2 years to < 18 years); * independently ambulatory adults (≥ 18 years); * Non-ambulatory adults (≥ 18 years) |
Who may qualify
- Ages
- 2 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- At least 1 year of pre-treatment medical history, including motor-function documentation, can be retrieved from the site electronic record.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Onasemnogene Abeparvovec-brveAlso: (ITVISMA®)administered once via lumbar puncture with systemic corticosteroid prophylaxis per label. | Drug | Onasemnogene Abeparvovec-brve |
Primary outcome
Change from baseline in HFMSE for independently ambulatory participants
Time frame: Baseline, 6, 12, 18 and 24 months
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
Time frame: Baseline, 6, 12, 18 and 24 months
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.
12 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Novartis Pharmaceuticals contact
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Onasemnogene Abeparvovec-brve in people with Spinal Muscular Atrophy, run by Novartis Pharmaceuticals at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Novartis Pharmaceuticals (1-888-669-6682, novartis.email@novartis.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in HFMSE for independently ambulatory participants (time frame: Baseline, 6, 12, 18 and 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.