Spinal Muscular AtrophyPhase 1STRONGNCT03381729

Study of Intrathecal Administration of Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy

A Phase 1 study testing Onasemnogene Abeparvovec-xioi in people with Spinal Muscular Atrophy, run by Novartis Gene Therapies at 11 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this trial is to evaluate the safety and tolerability of intrathecal administration of onasemnogene abeparvovec-xioi in infants and children with Spinal Muscular Atrophy with 3 copies of SMN2 and deletion of SMN1. Read more about this study

Who is it for?: Ages 6 to 60 months
Conditions the study is for: Spinal Muscular Atrophy
What is being tested?: Onasemnogene Abeparvovec-xioi
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 11 sitesUnited States
Study dates: 14 Dec 2017to 18 Nov 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 6 to 60 months
All sexes
No healthy volunteers
Child

Who may be able to join

Patients ≥6 months and up to 60 months (1800 days) of age at time of dosing following diagnostic confirmation during screening period by genotype who demonstrate the ability to sit unassisted for 10 or more seconds but cannot stand or walk
Diagnostic confirmation by genotype includes lab documentation of homozygous absence of SMN1 exon 7; with exactly three copies of SMN2
Negative gene testing for SMN2 gene modifier mutation (c.859G>C)
Onset of clinical signs and symptoms consistent with spinal muscular atrophy (SMA) at < 12 months of age
Able to sit independently and not standing or walking independently. Definition of sitting independently is defined by the World Health Organization Multicentre Growth Reference Study (WHO-MGRS) criteria of being able to sit up unsupported with head erect for at least 10 seconds. Child should not use arms or hands to balance body or support position (Wijnhoven 2004)
Be up-to-date on childhood vaccines that include palivizumab prophylaxis (also known as Synagis) to prevent respiratory syncytial virus (RSV) infections are also recommended in accordance with American Academy of Pediatrics (AAP 2009)

Who cannot join

Current or historical ability to stand or walk independently
Contraindications for spinal tap procedure or administration of intrathecal therapy or presence of an implanted shunt for the drainage of CSF or an implanted central venous (CNS) catheter
Severe contractures as determined by designated Physical Therapist(s) at screening that interfere with either the ability to attain/demonstrate functional measures or interferes with ability to receive intrathecal (IT) dosing
Severe scoliosis (defined as ≥ 50° curvature of spine) evident on X-ray examination
Previous, planned or expected scoliosis repair surgery/procedure within 1 year of dose administration
Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening while the patient is awake, or for high altitudes > 1000 m, oxygen saturation < 92% while the patient is awake

Show all 32Show fewer

Pulse oximetry saturation must not decrease ≥ four (4) percentage points between screening and highest value on day of dosing
Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods (i.e., nasogastric tube or nasojejunal tube) or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion
Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion
Active viral infection (includes human immunodeficiency virus (HIV) or serology positive for hepatitis B or C, or Zika virus)
Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization within two (2) weeks prior to study entry
Respiratory infection requiring medical attention, medical intervention or increase in supportive care of any manner within four (4) weeks prior to study entry
Severe non-pulmonary/respiratory tract infection within four (4) weeks before study dosing or concomitant illness that in the opinion of the Principal Investigator (PI) creates unnecessary risks for gene transfer such as:
Major renal or hepatic impairment
Known seizure disorder
Diabetes mellitus
Idiopathic hypocalciuria
Symptomatic cardiomyopathy
History of bacterial meningitis or brain or spinal cord disease, including tumors, or abnormalities by magnetic resonance imaging (MRI) or computerized tomography (CT) that would interfere with the lumbar puncture (LP) procedures or CSF circulation
Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
Known allergy or hypersensitivity to iodine or iodine-containing products
Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months of study dosing
Inability to withhold use of laxatives or diuretics in the 24 hours prior to dose administration
Anti-AAV9 antibody titers >1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay
Should a potential patient demonstrate anti AAV9 antibody titer > 1:50, he or she may receive retesting within 30 days of the screening period and will be eligible to participate if the anti AAV9 antibody titer upon retesting is ≤ 1:50
Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin > 2 × ULN, creatinine ≥ 1.0 mg/dL, hemoglobin [Hgb] < 8 or > 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy. Patients with an elevated bilirubin level that is unequivocally the result of neonatal jaundice shall not be excluded
Participation in recent SMA treatment clinical trial or receipt of an investigational or approved compound product or therapy received with the intent to treat SMA at any time prior to screening for this study
Oral beta agonists must be discontinued 30 days prior to dosing.
Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable and not a contraindication at any time prior to screening for this study
Expectation of major surgical procedures during the 1-year study assessment period

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

United States11 sites

Johns Hopkins
Baltimore, Maryland, 21287
Boston Children's Hospital
Boston, Massachusetts, 02115
Ann & Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
Nationwide Children's Hospital
Columbus, Ohio, 43205
UT Southwestern
Dallas, Texas, 75390
UCLA
Los Angeles, California, 90095
Nemours Children's Hospital
Orlando, Florida, 32827
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of Utah
Salt Lake City, Utah, 84112
Washington University
St Louis, Missouri, 63130
Stanford University
Stanford, California, 94305

Other trials in United States

About this study

Official title: Phase I, Open-Label, Dose Comparison Study of AVXS-101 for Sitting But Non-ambulatory Patients With Spinal Muscular Atrophy

Read the detailed description

This is a Phase 1, single-dose administration study of infants and children with a genetic diagnosis consistent with spinal muscular atrophy (SMA), bi-allelic deletion of survival motor neuron 1 gene (SMN1) and 3 copies of survival motor neuron 2 gene (SMN2) without the genetic modifier who are able to sit but cannot stand or walk at the time of study entry. Patients will receive onasemnogene abeparvovec-xioi in a dose comparison safety study of two (or three) potential therapeutic doses. Patients will be stratified in two groups, those ≥6 months and < 24 months of age at time of dosing and those ≥ 24 months and < 60 months of age at time of dosing. At least 15 patients ≥ 6 months and < 24 months, and at least 12 patients ≥ 24 < 60 months will be enrolled.

The first cohort will enroll three patients (Cohort 1) ≥ 6 months and < 24 months of age who will receive administration of 6.0 × 1013 vg of onasemnogene abeparvovec-xioi (Dose A). There will be at least a four week interval between the dosing of each patient within the cohort. Novartis Gene Therapies, Inc. will confer with the Data Safety Monitoring Board (DSMB) on all Grade III or higher AEs within approximately 48 hours of awareness that are possibly, probably or definitely related to the study agent before continuing enrollment. Safety data will be reviewed by the DSMB during quarterly meetings; following enrollment of the three patients and based upon the available safety data a decision will be made whether to: a) stop due to toxicity, or b) proceed to Cohort 2 using Dose B.

Should the determination be made to advance to Dose B, three patients < 60 months of age will be enrolled (Cohort 2) and will receive administration of 1.2 × 1014 vg of onasemnogene abeparvovec-xioi (Dose B). Again, there will be at least a four-week interval between dosing of the three patients within the cohort. Based on the available safety data from the three Cohort 2 patients and all of the Cohort 1 patients, the DSMB will decide and document during quarterly meetings whether further four-week intervals between patients dosing is necessary. Novartis Gene Therapies, Inc. will take this recommendation into consideration and will make the final determination whether to persist with four-week intervals between patients dosing going forward; the decision will be communicated to sites and Institutional Review Boards (IRBs) in a formal sponsor letter. Novartis Gene Therapies, Inc. will confer with the DSMB on all Grade III or higher AEs within approximately 48 hours of awareness that are possibly, probably or definitely related to the study agent before continuing enrollment. Safety data will be reviewed by the DSMB during quarterly meetings; following enrollment of the first six patients and based upon available safety data, a decision will be made whether to: a) stop due to toxicity, or b) continue to enroll an additional 21 patients until there are a total of 12 patients > 6 months and < 24 months and 12 patients ≥ 24 and < 60 months that have all received Dose B.

Based upon an ongoing assessment of safety and efficacy data from patients treated with the 1.2 × 1014 vg dose, an option for testing of a third dose (Dose C), will be considered. If, based on all available data, this is judged to be safe and necessary, three patients < 60 months of age will receive Dose C, 2.4 × 1014 vg administered IT. A meeting of the DSMB will be called to obtain a recommendation on the safety of escalating to a higher dose prior to proceeding. If a decision is made to proceed to testing a higher dose, there will again be a four-week interval between dosing of the first three patients receiving Dose C, as in Cohorts 1 and 2. Safety data will be reviewed by the DSMB during quarterly meetings. Following enrollment of the first three Dose C patients and based upon available safety data, the DSMB will be consulted and a decision will be made whether to: a) stop dosing Dose C due to safety concerns, or b) continue to enroll an additional 21 patients until there are a total of 12 patients > 6 months and < 24 months and 12 patients ≥ 24 and < 60 months that have received Dose C.

Patients from Cohort 3 will be followed for a total of 15 months post-dose. The primary analyses for efficacy will be assessed when all patients reach 12 months post-dose and the primary analyses for safety will be assessed when the last patient of Cohort 3 reaches 15 months post-dose (and database lock will be performed after the last patient reaches 15 months post-dose).

Conditions: Spinal Muscular Atrophy
Being tested: Onasemnogene Abeparvovec-xioi
Keywords: Gene Transfer, Gene Therapy, Adeno-associated virus, Survival Motor Neuron, SMN, AAV9
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-xioiBiological
Also called Zolgensma
Self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter

Study groups in NCT03381729
Study group	Role	What they receive
Dose A	Experimental	Intrathecal administration 6.0 X 10^13 vg of onasemnogene abeparvovec-xioi Receives: Biological: Onasemnogene Abeparvovec-xioi
Dose B	Experimental	Intrathecal administration 1.2 X 10^14 vg of onasemnogene abeparvovec-xioi Receives: Biological: Onasemnogene Abeparvovec-xioi
Dose C	Experimental	Intrathecal administration 2.4 X 10^14 vg of onasemnogene abeparvovec-xioi Receives: Biological: Onasemnogene Abeparvovec-xioi

What is being measured

The primary outcome is the main question the study is designed to answer.

Age 6 to <24 Months Only: Number of Participants Who Achieved the Ability to Stand Alone
Defined by the Bayley Scales of Infant and Toddler Development (BSID) Gross Motor (GM) subtest performance criteria number 40, confirmed by video recording, as a participant who stands alone for at least 3 seconds unsupported.
Measured: From Day 1 up to Month 12
Age 24 to <60 Months Only: Change From Baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) Score at Month 12
The HFMSE contained 33 items which were scored on a scale of 0-2 with a total achievable score ranging from 0, if all activities are failed, to 66, if all the activities are achieved. A positive change from baseline indicates a better outcome.
Measured: Baseline and Month 12
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as any event that began or worsened in severity on or after the administration of AVXS-101 through the last study visit.
Evaluation of TEAEs included the number of participants with at least one:
- TEAE
- Serious TEAE
- TEAE related to AVXS-101
- TEAE with Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 (grade 3 = severe or medically significant to grade 5 = death related to TEAE)
Measured: Adverse events were collected from the single dose of study treatment until the end of study visit (12 months for Cohort 1 and 2 and 15 months for Cohort 3)

Secondary outcomes (2)

Number of Participants Who Achieved the Ability to Walk Alone
Defined by the BSID GM subtest performance criteria number 43, confirmed by video recording, as a participant who takes 5 coordinated independent steps.
Measured: From Day 1 up to Month 12
Average Number of Hours Per Day of Non-invasive Ventilatory Support
Participants were assessed by a pulmonologist and may have been fitted with a non-invasive positive pressure ventilatory (e.g., Bilevel Positive Airway Pressure BiPAP) at the discretion of the pulmonologist and/or investigator. The number of hours per day of non-invasive ventilatory support was captured continuously by the device.
Measured: Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Dec 201718 Nov 2021

First posted22 Dec 2017
Study start14 Dec 2017
Primary completion18 Nov 2021
Study completion18 Nov 2021

Why it stopped: Based upon overall strategic objectives within the broader intrathecal clinical development program, Novartis Gene Therapies decided to terminate the study early.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03381729
Sponsor's protocol ID: AVXS-101-CL-102
Other IDs: 2020-003678-28, COAV101A12102
Acronym: STRONG
Status last verified: Jan 2026
First submitted: 13 Dec 2017
Last updated: 26 Jan 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Duque SI, Arnold WD, Odermatt P, Li X, Porensky PN, Schmelzer L, Meyer K, Kolb SJ, Schumperli D, Kaspar BK, Burghes AH. A large animal model of spinal muscular atrophy and correction of phenotype. Ann Neurol. 2015 Mar;77(3):399-414. doi: 10.1002/ana.24332. Epub 2015 Feb 9.
PubMed 25516063
Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271-4. doi: 10.1038/nbt.1610. Epub 2010 Feb 28.
PubMed 20190738
Meyer K, Ferraiuolo L, Schmelzer L, Braun L, McGovern V, Likhite S, Michels O, Govoni A, Fitzgerald J, Morales P, Foust KD, Mendell JR, Burghes AH, Kaspar BK. Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates. Mol Ther. 2015 Mar;23(3):477-87. doi: 10.1038/mt.2014.210. Epub 2014 Oct 31.
PubMed 25358252

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Spinal Muscular Atrophy trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I, Open-Label, Dose Comparison Study of AVXS-101 for Sitting But Non-ambulatory Patients With Spinal Muscular Atrophy
ClinicalTrials.gov ID: NCT03381729
Acronym / sponsor ID: STRONG / AVXS-101-CL-102
Conditions: Spinal Muscular Atrophy
Keywords: Gene Transfer, Gene Therapy, Adeno-associated virus, Survival Motor Neuron, SMN, AAV9
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Based upon overall strategic objectives within the broader intrathecal clinical development program, Novartis Gene Therapies decided to terminate the study early.
Enrolment: 32 participants (actual)
Lead sponsor: Novartis Gene TherapiesIndustry (pharma, biotech, devices)
Study start: 14 Dec 2017 (actual)
Primary completion: 18 Nov 2021 (actual)
Study completion: 18 Nov 2021 (actual)
First posted: 22 Dec 2017 (actual)
Results: Posted 16 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Dose A	Experimental	Biological: Onasemnogene Abeparvovec-xioiIntrathecal administration 6.0 X 10^13 vg of onasemnogene abeparvovec-xioi
Dose B	Experimental	Biological: Onasemnogene Abeparvovec-xioiIntrathecal administration 1.2 X 10^14 vg of onasemnogene abeparvovec-xioi
Dose C	Experimental	Biological: Onasemnogene Abeparvovec-xioiIntrathecal administration 2.4 X 10^14 vg of onasemnogene abeparvovec-xioi

Who may qualify

Ages: 6 to 60 months
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

Patients ≥6 months and up to 60 months (1800 days) of age at time of dosing following diagnostic confirmation during screening period by genotype who demonstrate the ability to sit unassisted for 10 or more seconds but cannot stand or walk
Diagnostic confirmation by genotype includes lab documentation of homozygous absence of SMN1 exon 7; with exactly three copies of SMN2
Negative gene testing for SMN2 gene modifier mutation (c.859G>C)
Onset of clinical signs and symptoms consistent with spinal muscular atrophy (SMA) at < 12 months of age
Able to sit independently and not standing or walking independently. Definition of sitting independently is defined by the World Health Organization Multicentre Growth Reference Study (WHO-MGRS) criteria of being able to sit up unsupported with head erect for at least 10 seconds. Child should not use arms or hands to balance body or support position (Wijnhoven 2004)

Key exclusion criteria (32 listed)

Current or historical ability to stand or walk independently
Contraindications for spinal tap procedure or administration of intrathecal therapy or presence of an implanted shunt for the drainage of CSF or an implanted central venous (CNS) catheter
Severe contractures as determined by designated Physical Therapist(s) at screening that interfere with either the ability to attain/demonstrate functional measures or interferes with ability to receive intrathecal (IT) dosing
Severe scoliosis (defined as ≥ 50° curvature of spine) evident on X-ray examination
Previous, planned or expected scoliosis repair surgery/procedure within 1 year of dose administration

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-xioiAlso: ZolgensmaSelf-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-β-actin promoter	Biological	Dose A, Dose B, Dose C

Primary outcome

Age 6 to <24 Months Only: Number of Participants Who Achieved the Ability to Stand Alone
Time frame: From Day 1 up to Month 12
Defined by the Bayley Scales of Infant and Toddler Development (BSID) Gross Motor (GM) subtest performance criteria number 40, confirmed by video recording, as a participant who stands alone for at least 3 seconds unsupported.
Age 24 to <60 Months Only: Change From Baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) Score at Month 12
Time frame: Baseline and Month 12
The HFMSE contained 33 items which were scored on a scale of 0-2 with a total achievable score ranging from 0, if all activities are failed, to 66, if all the activities are achieved. A positive change from baseline indicates a better outcome.
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Time frame: Adverse events were collected from the single dose of study treatment until the end of study visit (12 months for Cohort 1 and 2 and 15 months for Cohort 3)
A TEAE was defined as any event that began or worsened in severity on or after the administration of AVXS-101 through the last study visit. Evaluation of TEAEs included the number of participants with at least one: * TEAE * Serious TEAE * TEAE related to AVXS-101 * TEAE with Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 (grade 3 = severe or medically significant to grade 5 = death related to TEAE)

2 secondary outcomes

Number of Participants Who Achieved the Ability to Walk Alone
Time frame: From Day 1 up to Month 12
Average Number of Hours Per Day of Non-invasive Ventilatory Support
Time frame: Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

Results and safety

Results posted to the registry on 16 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	3	3
Cohort 2: 1.2E14 vg - Age 6 to <24 Months	13	13
Cohort 2: 1.2E14 vg - Age 24 to <60 Months	12	12
Cohort 3: 2.4E14 vg - Age 6 to <24 Months	4	4
Cohort 3: 2.4E14 vg - Age 24 to <60 Months	0	0

Primary outcome: Age 6 to <24 Months Only: Number of Participants Who Achieved the Ability to Stand Alone

Time frame: From Day 1 up to Month 12. Count of participants. Unit: Participants

Measure	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months n = 3	Cohort 2: 1.2E14 vg - Age 6 to <24 Months n = 13	Cohort 3: 2.4E14 vg - Age 6 to <24 Months n = 4
Able to Stand Alone	1	1	0
Unable to Stand Alone	2	12	4

Cohort 2: 1.2E14 vg - Age 6 to <24 Months: Difference in Percent: -6.0 (95% CI -21.8 to 22.8), p >0.9999, Fisher Exact

Population analysed: Intent-to-Treat (ITT) Set: All enrolled participants who were given an AVXS-101 intrathecal injection. Participants were analyzed according to the assigned dose. Data were only collected in participants aged 6 to \<24 months at time of dosing.

Primary outcome: Age 24 to <60 Months Only: Change From Baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) Score at Month 12

Time frame: Baseline and Month 12. Least squares mean (95% Confidence Interval). Unit: score on a scale

Measure	Cohort 2: 1.2E14 vg - Age 24 to <60 Months n = 12
Value	6.0 (3.7 to 8.3)

Cohort 2: 1.2E14 vg - Age 24 to <60 Months: Difference Between Least Squares Mean: 5.5 (95% CI 1.9 to 9.0), p = 0.0027, Mixed-Model Repeat Measure

Population analysed: ITT Set: All enrolled participants who were given an AVXS-101 intrathecal injection. Participants were analyzed according to the assigned dose. Data were only collected in participants aged 24 to \<60 months at time of dosing.

Primary outcome: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

Time frame: Adverse events were collected from the single dose of study treatment until the end of study visit (12 months for Cohort 1 and 2 and 15 months for Cohort 3). Count of participants. Unit: Participants

Measure	Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months n = 3	Cohort 2: 1.2E14 vg - Age 6 to <24 Months n = 13	Cohort 2: 1.2E14 vg - Age 24 to <60 Months n = 12	Cohort 3: 2.4E14 vg - Age 6 to <24 Months n = 4
TEAE	3	13	12	4
Serious TEAE	1	2	4	0
TEAE Related to AVXS-101	0	7	4	1
TEAE with CTCAE Grade ≥ 3	1	4	4	0

Population analysed: Safety Analysis Set: All participants given an AVXS-101 intrathecal injection. Participants were analyzed according to actual dose received.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the single dose of study treatment until the end of study visit (12 months for Cohort 1 and 2 and 15 months for Cohort 3). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: 6.0E13 Vector Genomes (vg) - Age 6 to <24 Months	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Cohort 2: 1.2E14 vg - Age 6 to <24 Months	2 of 13 (15.4%)	13 of 13 (100%)	0 of 13
Cohort 2: 1.2E14 vg - Age 24 to <60 Months	4 of 12 (33.3%)	12 of 12 (100%)	0 of 12
Cohort 3: 2.4E14 vg - Age 6 to <24 Months	0 of 4 (0%)	4 of 4 (100%)	0 of 4

Limitations and caveats (from the sponsor): A comparison of the results from this study to the results from the natural history observational study (Pediatric Neuromuscular Clinical Research Network (PNCR), Finkel et al, 2014) are included in the Novartis Clinical Trial Results, as a historical control. These full results are available via this link: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17933

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25516063Duque SI, Arnold WD, Odermatt P, Li X, Porensky PN, Schmelzer L, Meyer K, Kolb SJ, Schumperli D, Kaspar BK, Burghes AH. A large animal model of spinal muscular atrophy and correction of phenotype. Ann Neurol. 2015 Mar;77(3):399-414. doi: 10.1002/ana.24332. Epub 2015 Feb 9.
Background: PubMed 20190738Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271-4. doi: 10.1038/nbt.1610. Epub 2010 Feb 28.
Background: PubMed 25358252Meyer K, Ferraiuolo L, Schmelzer L, Braun L, McGovern V, Likhite S, Michels O, Govoni A, Fitzgerald J, Morales P, Foust KD, Mendell JR, Burghes AH, Kaspar BK. Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates. Mol Ther. 2015 Mar;23(3):477-87. doi: 10.1038/mt.2014.210. Epub 2014 Oct 31.
The Novartis Clinical Trial ResultsLink provided by the sponsor.
A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.

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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. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Onasemnogene Abeparvovec-xioi in people with Spinal Muscular Atrophy, run by Novartis Gene Therapies at 11 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 6 inclusion and 32 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: stopped early, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Age 6 to <24 Months Only: Number of Participants Who Achieved the Ability to Stand Alone (time frame: From Day 1 up to Month 12). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03381729, which also lists 3 linked publications.

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 26 Jan 2026.