Spinal Muscular AtrophyPhase 3STRENGTHNCT05386680
Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam
A Phase 3 study testing OAV101 in people with Spinal Muscular Atrophy, run by Novartis Pharmaceuticals at 13 sites in 9 countries.
Trial summary
This was a Phase IIIb open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101B in participants with SMA aged 2 to <18 years after the discontinuation of treatment with nusinersen or risdiplam. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- OAV101
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 13 sitesin 9 countries
- Study dates
- 12 Jan 2023to 29 Nov 2024
- 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 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- SMA diagnosis
- Aged 2 to < 18 years
- Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
- Must have symptoms of SMA as defined in the protocol
Who cannot join
- Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated
- Clinically significant abnormalities in test results during screening
- Contraindications for lumbar puncture procedure
- At Baseline, participants are excluded if they received:
- nusinersen (Spinraza®) or
- risdiplam (Evrysdi®) within a defined timeframe
Show all 10Show fewer
- Vaccinations 2 weeks prior to administration of OAV101
- Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.
- Presence of an infection or febrile illness up to 30 days prior to administration of OAV101
- Requiring invasive ventilation
Trial locations and contacts
13 sites in 9 countries.
13 sites in 9 countries
United States3 sites
Boston Childrens Hospital
Boston, Massachusetts, 02215
University of Wisconsin Madison Medical School
Madison, Wisconsin, 53792-7375
Child Hosp Of The Kings Daughters
Norfolk, Virginia, 23507
France2 sites
Novartis Investigative Site
Bron, 69677
Novartis Investigative Site
Toulouse, 31059
Japan2 sites
Novartis Investigative Site
Kurume, Fukuoka, 830-0011
Novartis Investigative Site
Shinjuku Ku, Tokyo, 162 8666
About this study
Official title: Phase IIIb, Open-label, Single-arm, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally (1.2 x 10^14 Vector Genomes) to Participants 2 to < 18 Years of Age With Spinal Muscular Atrophy (SMA) Who Have Discontinued Treatment With Nusinersen (Spinraza®) or Risdiplam (Evrysdi®)
This was a Phase IIIb open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101B in participants with SMA aged 2 to <18 years after the discontinuation of treatment with nusinersen or risdiplam. The study aimed to enroll approximately 28 participants across each of 2 age brackets (2 to <6 years, and 6 to <18 years).
Read the detailed description
Eligible participants received a single OAV101B administration of 1.2x1014 vector genomes on Day 1 (Treatment period) and were followed for a period of 52 weeks.
Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101B on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, based on Investigator judgment.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- OAV101
- Keywords
- Zolgensma, OAV101, AVXS 101, gene therapy, Muscle atrophy, SBMA, spinal and bulbar muscular atrophy, spinal muscular atrophy, bulbar muscular atrophy, muscle function, myopathy, muscle wasting, atrophied muscle, loss of muscle strength, SMA
- Medical subject headings
- Muscular Atrophy, Spinal, Muscular Atrophy, Bulbo-Spinal Atrophy, X-Linked, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OAV101Genetic
Also called AVXS-101, Zolgensma
Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose
| Study group | Role | What they receive |
|---|---|---|
| OAV-101 | Experimental | Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose Receives: Genetic: OAV101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overview of Treatment-emergent Adverse Events by Age Subgroup
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
Measured: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
Measured: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
An adverse event of special interest (AESI) is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Transient thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, signs and symptoms that may be suggestive dorsal root ganglia toxicity, and new malignancies.
Measured: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
Secondary outcomes (6)
Change From Baseline at Week 52 Visit in the HFMSE Total Score - Mean (SD)
The Hammersmith Functional Motor Scale Expanded (HFMSE) is a SMA-specific 33-item assessment that is administered by qualified clinical evaluators. Each motor skill item is scored on a 3-point Likert scale from 0 (no response) to 2 (full response), with a total score range of 0 to 66. A higher score indicates a higher ability level.
Measured: Baseline, Week 52
Change From Baseline at Week 52 Visit in the HFMSE Total Score - LS Means
The Hammersmith Functional Motor Scale Expanded (HFMSE) is a SMA-specific 33-item assessment that is administered by qualified clinical evaluators. Each motor skill item is scored on a 3-point Likert scale from 0 (no response) to 2 (full response), with a total score range of 0 to 66. A higher score indicates a higher ability level.
Measured: Baseline, Week 52
Change From Baseline at Week 52 Visit in the RULM Total Score - Mean (SD)
The Revised Upper Limb Model (RULM) is a validated, SMA-specific assessment that measures motor performance in the upper limbs from childhood through adulthood in ambulatory and never ambulatory individuals with SMA. The revised version of the test consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). These item scores are summed to give a total score ranging from 0 to 37 points with lower scores reflecting poorer ability.
Measured: Baseline, Week 52
Change From Baseline at Week 52 Visit in the RULM Total Score - LS Means
The Revised Upper Limb Model (RULM) is a validated, SMA-specific assessment that measures motor performance in the upper limbs from childhood through adulthood in ambulatory and never ambulatory individuals with SMA. The revised version of the test consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). These item scores are summed to give a total score ranging from 0 to 37 points with lower scores reflecting poorer ability.
Measured: Baseline, Week 52
Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - Mean (SD)
The Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument quantifies the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA. The total score is on a scale of 0 to 100 with a higher score indicating that caregivers experienced less intense caregiving impact.
Measured: Baseline, Week 52
Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - LS Means
The Assessment of Caregiver Experience in Neuromuscular Disease (ACEND) instrument quantifies the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA. The total score is on a scale of 0 to 100 with a higher score indicating that caregivers experienced less intense caregiving impact.
Measured: Baseline, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2022
- Study start12 Jan 2023
- Primary completion29 Nov 2024
- Study completion29 Nov 2024
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 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05386680
- Sponsor's protocol ID
- COAV101B12302
- Acronym
- STRENGTH
- Status last verified
- Dec 2025
- First submitted
- 18 May 2022
- Last updated
- 13 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
Kwon JM, Munell F, Le Goff L, Yuge K, Kato T, Cances C, De Waele L, Woodcock IR, Mercuri EM, Proud CM, Darras BT, Hayes LH, Oskoui M, Visootsak J, Williams G, Ilic A, Yang L, van der Pol WL. Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial. Nat Med. 2026 Feb;32(2):488-493. doi: 10.1038/s41591-025-04119-2. Epub 2025 Dec 8.
PubMed 41360995
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIIb, Open-label, Single-arm, Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally (1.2 x 10^14 Vector Genomes) to Participants 2 to < 18 Years of Age With Spinal Muscular Atrophy (SMA) Who Have Discontinued Treatment With Nusinersen (Spinraza®) or Risdiplam (Evrysdi®)
- ClinicalTrials.gov ID
- NCT05386680
- Acronym / sponsor ID
- STRENGTH / COAV101B12302
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Zolgensma, OAV101, AVXS 101, gene therapy, Muscle atrophy, SBMA, spinal and bulbar muscular atrophy, spinal muscular atrophy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Jan 2023 (actual)
- Primary completion
- 29 Nov 2024 (actual)
- Study completion
- 29 Nov 2024 (actual)
- First posted
- 23 May 2022 (actual)
- Results
- Posted 3 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase IIIb open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101B in participants with SMA aged 2 to <18 years after the discontinuation of treatment with nusinersen or risdiplam. The study aimed to enroll approximately 28 participants across each of 2 age brackets (2 to <6 years, and 6 to <18 years).
Detailed description
Eligible participants received a single OAV101B administration of 1.2x1014 vector genomes on Day 1 (Treatment period) and were followed for a period of 52 weeks.
Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101B on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, based on Investigator judgment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OAV-101 | Experimental | Genetic: OAV101Intrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- SMA diagnosis
- Aged 2 to < 18 years
- Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
- Must have symptoms of SMA as defined in the protocol
Key exclusion criteria (10 listed)
- Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated
- Clinically significant abnormalities in test results during screening
- Contraindications for lumbar puncture procedure
- At Baseline, participants are excluded if they received:
- Vaccinations 2 weeks prior to administration of OAV101
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 |
|---|---|---|
| OAV101Also: AVXS-101, ZolgensmaIntrathecal administration of OAV101 at a dose of 1.2 x 10^14 vector genomes, one time dose | Genetic | OAV-101 |
Primary outcome
Overview of Treatment-emergent Adverse Events by Age Subgroup
Time frame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)
Time frame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.
Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup
Time frame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments. An adverse event of special interest (AESI) is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Transient thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, signs and symptoms that may be suggestive dorsal root ganglia toxicity, and new malignancies.
6 secondary outcomes
Change From Baseline at Week 52 Visit in the HFMSE Total Score - Mean (SD)
Time frame: Baseline, Week 52
Change From Baseline at Week 52 Visit in the HFMSE Total Score - LS Means
Time frame: Baseline, Week 52
Change From Baseline at Week 52 Visit in the RULM Total Score - Mean (SD)
Time frame: Baseline, Week 52
Change From Baseline at Week 52 Visit in the RULM Total Score - LS Means
Time frame: Baseline, Week 52
Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - Mean (SD)
Time frame: Baseline, Week 52
Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - LS Means
Time frame: Baseline, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41360995Kwon JM, Munell F, Le Goff L, Yuge K, Kato T, Cances C, De Waele L, Woodcock IR, Mercuri EM, Proud CM, Darras BT, Hayes LH, Oskoui M, Visootsak J, Williams G, Ilic A, Yang L, van der Pol WL. Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial. Nat Med. 2026 Feb;32(2):488-493. doi: 10.1038/s41591-025-04119-2. Epub 2025 Dec 8.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- A Pediatric 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.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing OAV101 in people with Spinal Muscular Atrophy, run by Novartis Pharmaceuticals at 13 sites in 9 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 4 inclusion and 10 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 13 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 13 sites in United States, France, Japan, Australia, Belgium and 4 more countries. 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 3 Jun 2025). 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?
Overview of Treatment-emergent Adverse Events by Age Subgroup (time frame: Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.). 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 NCT05386680, 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 13 Jan 2026.