Spinal Muscular Atrophy Type IPhase 3NCT03837184
Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
A Phase 3 study testing Onasemnogene Abeparvovec-xioi in people with Spinal Muscular Atrophy Type I, run by Novartis Gene Therapies at 4 sites in 3 countries.
Trial summary
This is a Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in participants with spinal muscular atrophy (SMA) Type 1 and who are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of… Read more about this study
- Who is it for?
- Ages 0 days to 6 months
- Conditions the study is for
- Spinal Muscular Atrophy Type I
- What is being tested?
- Onasemnogene Abeparvovec-xioi
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 31 May 2019to 29 Jun 2021
- Phase
- Phase 3
- 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 0 days to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participants with SMA Type 1 as determined by diagnosis of SMA based on gene mutation analysis with biallelic SMN1 mutations (deletion or point mutations) and one or 2 copies of SMN2 [inclusive of the known SMN2 gene modifier mutation (c.859G>C)]
- Participants must be < 6 months (< 180 days) of age at the time of onasemnogene abeparvovec-xioi infusion
- Participants must have a swallowing evaluation test performed prior to administration of gene replacement therapy
- Up-to-date on childhood vaccinations as per local health authorities.
- Parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with trial procedures and visit schedule
Who cannot join
- Previous, planned or expected scoliosis repair surgery/procedure prior to 18 months of age
- Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening:
- Pulse oximetry saturation must not decrease ≥ 4 percentage points between screening and dosing with confirmatory oximetry reading
- Participants may be put on non-invasive ventilatory support for less than 12 hours per day at the discretion of their physician or trial staff
- Use or requirement of non-invasive ventilatory support for greater than or equal to 12 hours daily in the two weeks prior to dosing
- Participant with signs of aspiration based on a swallowing test or whose weight-for-age falls below the 3rd percentile based on World Health Organization (WHO) Child Growth Standards and unwilling to use an alternative method to oral feeding
Show all 25Show fewer
- Active viral infection (includes human immunodeficiency virus [HIV] or positive serology for hepatitis B, C, or E, or known Zika virus infection)
- Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization within 2 weeks prior to screening
- Upper or lower respiratory infection requiring medical attention, medical intervention, or increase in supportive care of any manner within 4 weeks prior to screening
- Severe non-pulmonary/respiratory tract infection (eg, pyelonephritis, or meningitis) within 4 weeks before administration of gene replacement therapy or concomitant illness that, in the opinion of the Principal Investigator, creates unnecessary risks for gene replacement such as:
- Major renal or hepatic impairment
- Known seizure disorder
- Diabetes mellitus
- Idiopathic hypocalcuria
- Symptomatic cardiomyopathy
- Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients, or human, animal biological raw materials (human transferrin, human insulin, trypsin derived from porcine spleen, bovine derived protein (FBS, bovine milk-derived Benzonase, casamino acid, bovine pancreas), HEK 293 cells, Cosmic Calf Serum, HyQtase) used in manufacturing of onasemnogene abeparvovec-xioi product
- 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 prior to gene replacement therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IV immunoglobulin, rituximab)
- Anti-AAV9 antibody titer > 1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. Should a potential participant 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 (gamma-glutamyl transpeptidase [GGT], ALT, AST, total bilirubin > 2x the 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 (with the exception of observational cohort studies or non-interventional studies) or receipt of an investigational or commercial compound, product or therapy administered with the intent to treat SMA (e.g., nusinersen, valproic acid) at any time prior to screening for this trial. Oral beta-agonists must be discontinued at least 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 trial
- Expectation of major surgical procedures during the trial assessment period (e.g., spinal surgery or tracheostomy)
- Parent(s)/legal guardian(s) unable or unwilling to comply with trial procedures or inability to travel for repeat visits
- Parent(s)/legal guardian(s) unwilling to keep trial results/observations confidential or to refrain from posting confidential trial results/observations on social media sites
- Parent(s)/legal guardian(s) refuses to sign consent form
- Participants < 35 weeks gestational age at time of birth
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
South Korea2 sites
Seoul National University Hospital
Seoul
Pusan National University Yangsan Hospital
Yangsan, Gyeongsangnam-do
About this study
Official title: Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion
This is a Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in participants with spinal muscular atrophy (SMA) Type 1 and who are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). The primary objective of the study is to evaluate the efficacy of onasemnogene abeparvovec-xioi by assessing the proportion of symptomatic SMA Type 1 participants who achieve the ability to sit unaided for at least 10 seconds up to and including the 18 months of age trial visit. At least 6 participants aged < 6 months (< 180 days) at the time of gene replacement therapy (Day 1) will be enrolled.
Read the detailed description
This is a Phase 3, open-label, single-arm, single-dose trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in participants with SMA Type 1 with one or 2 copies of SMN2. At least 6 participants < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.
The trial includes 3 trial periods: screening, gene replacement therapy, and follow-up. During the screening period (Days -30 to -2), participants whose parent(s)/legal guardian(s) provide informed consent will undergo screening procedures to determine eligibility for trial enrollment. participants who meet the entry criteria will enter the in-patient gene replacement therapy period (Day -1 to Day 3). On Day -1, participants will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, participants will receive a one-time intravenous (IV) infusion of the equivalent of onasemnogene abeparvovec-xioi cohort 2 dose received in the AVXS-101-CL-101 trial over approximately 60 minutes and will undergo in-patient safety monitoring over the next 48 hours. Participants may be discharged 48 hours after gene replacement therapy, based on Investigator judgment. During the outpatient follow-up period (Days 4 to End of Trial at 18 months of age), participants will return at regularly scheduled intervals for efficacy and safety assessments until the participant reaches 18 months of age.
- Conditions
- Spinal Muscular Atrophy Type I
- Being tested
- Onasemnogene Abeparvovec-xioi
- Keywords
- Spinal Muscular Atrophy, SMN2, Onasemnogene Abeparvovec-xioi, Gene replacement therapy
- Medical subject headings
- Spinal Muscular Atrophies of Childhood, 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
Onasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the human survival motor neuron (SMN) gene under the control of the cytomegalovirus (CMV) enhancer/chicken β-actin-hybrid promoter (CB). Onasemnogene abeparvovec-xioi will be administered as a one-time intravenous infusion over approximately 60 minutes. Dosage will be determined by the participants weight.
| Study group | Role | What they receive |
|---|---|---|
| Onasemnogene Abeparvovec-xioi | Experimental | Participants will receive a single dose of onasemnogene abeparvovec-xioi, administered intravenously. Receives: Biological: Onasemnogene Abeparvovec-xioi |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Achieved Sitting Alone for at Least 10 Seconds
Independent sitting is defined by the World Health Organization Multicentre Growth Reference Study, confirmed by video recording, as a participant who sits up straight unsupported for at least 10 seconds.
Measured: From Baseline up to 18 Months of Age Visit
Secondary outcomes (1)
Event-free Survival at 14 Months of Age
Event-free survival at 14 months of age was defined as the number of participants who did not die, did not require permanent ventilation and did not withdraw from the study by 14 months of age.
Measured: From Baseline up to 14 Months of Age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2019
- Study start31 May 2019
- Primary completion29 Jun 2021
- Study completion29 Jun 2021
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 (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular Atrophy Type IStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Gene Therapies
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03837184
- Sponsor's protocol ID
- AVXS-101-CL-306
- Other IDs
- 194664, 201900208, COAV101A12304
- Status last verified
- Jan 2026
- First submitted
- 8 Feb 2019
- Last updated
- 26 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 https://www.clinicalstudydatarequest.com/.
Publications
Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12.
PubMed 34383289
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 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion
- ClinicalTrials.gov ID
- NCT03837184
- Acronym / sponsor ID
- AVXS-101-CL-306
- Conditions
- Spinal Muscular Atrophy Type I
- Keywords
- Spinal Muscular Atrophy, SMN2, Onasemnogene Abeparvovec-xioi, Gene replacement therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Novartis Gene TherapiesIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 31 May 2019 (actual)
- Primary completion
- 29 Jun 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 12 Feb 2019 (actual)
- Results
- Posted 11 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3, open-label, single-arm, single-dose, trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in participants with spinal muscular atrophy (SMA) Type 1 and who are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). The primary objective of the study is to evaluate the efficacy of onasemnogene abeparvovec-xioi by assessing the proportion of symptomatic SMA Type 1 participants who achieve the ability to sit unaided for at least 10 seconds up to and including the 18 months of age trial visit. At least 6 participants aged < 6 months (< 180 days) at the time of gene replacement therapy (Day 1) will be enrolled.
Detailed description
This is a Phase 3, open-label, single-arm, single-dose trial of onasemnogene abeparvovec-xioi (gene replacement therapy) in participants with SMA Type 1 with one or 2 copies of SMN2. At least 6 participants < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.
The trial includes 3 trial periods: screening, gene replacement therapy, and follow-up. During the screening period (Days -30 to -2), participants whose parent(s)/legal guardian(s) provide informed consent will undergo screening procedures to determine eligibility for trial enrollment. participants who meet the entry criteria will enter the in-patient gene replacement therapy period (Day -1 to Day 3). On Day -1, participants will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, participants will receive a one-time intravenous (IV) infusion of the equivalent of onasemnogene abeparvovec-xioi cohort 2 dose received in the AVXS-101-CL-101 trial over approximately 60 minutes and will undergo in-patient safety monitoring over the next 48 hours. Participants may be discharged 48 hours after gene replacement therapy, based on Investigator judgment. During the outpatient follow-up period (Days 4 to End of Trial at 18 months of age), participants will return at regularly scheduled intervals for efficacy and safety assessments until the participant reaches 18 months of age.
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-xioi | Experimental | Biological: Onasemnogene Abeparvovec-xioiParticipants will receive a single dose of onasemnogene abeparvovec-xioi, administered intravenously. |
Who may qualify
- Ages
- 0 days to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Participants with SMA Type 1 as determined by diagnosis of SMA based on gene mutation analysis with biallelic SMN1 mutations (deletion or point mutations) and one or 2 copies of SMN2 [inclusive of the known SMN2 gene modifier mutation (c.859G>C)]
- Participants must be < 6 months (< 180 days) of age at the time of onasemnogene abeparvovec-xioi infusion
- Participants must have a swallowing evaluation test performed prior to administration of gene replacement therapy
- Up-to-date on childhood vaccinations as per local health authorities.
- Parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with trial procedures and visit schedule
Key exclusion criteria (25 listed)
- Previous, planned or expected scoliosis repair surgery/procedure prior to 18 months of age
- Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening:
- Use or requirement of non-invasive ventilatory support for greater than or equal to 12 hours daily in the two weeks prior to dosing
- Participant with signs of aspiration based on a swallowing test or whose weight-for-age falls below the 3rd percentile based on World Health Organization (WHO) Child Growth Standards and unwilling to use an alternative method to oral feeding
- Active viral infection (includes human immunodeficiency virus [HIV] or positive serology for hepatitis B, C, or E, or known Zika virus infection)
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: ZolgensmaOnasemnogene abeparvovec-xioi is a non-replicating recombinant adeno-associated virus serotype 9 (AAV9) containing the human survival motor neuron (SMN) gene under the control of the cytomegalovirus (CMV) enhancer/chicken β-actin-hybrid promoter (CB). Onasemnogene abeparvovec-xioi will be administered as a one-time intravenous infusion over approximately 60 minutes. Dosage will be determined by the participants weight. | Biological | Onasemnogene Abeparvovec-xioi |
Primary outcome
Number of Participants Who Achieved Sitting Alone for at Least 10 Seconds
Time frame: From Baseline up to 18 Months of Age Visit
Independent sitting is defined by the World Health Organization Multicentre Growth Reference Study, confirmed by video recording, as a participant who sits up straight unsupported for at least 10 seconds.
1 secondary outcome
Event-free Survival at 14 Months of Age
Time frame: From Baseline up to 14 Months of Age
Results and safety
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.
- Derived from this study: PubMed 34383289Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12.
- Novartis Clinical Trial ResultsLink provided by the sponsor.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- 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 https://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. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Onasemnogene Abeparvovec-xioi in people with Spinal Muscular Atrophy Type I, run by Novartis Gene Therapies at 4 sites in 3 countries.
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 5 inclusion and 25 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: finished, 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 4 sites in South Korea, Japan, Taiwan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 11 Jan 2022). 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?
Number of Participants Who Achieved Sitting Alone for at Least 10 Seconds (time frame: From Baseline up to 18 Months of Age Visit). 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 NCT03837184, which also lists 1 linked publication.
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.