Spinal Muscular AtrophyPhase 3ASCENDNCT05067790
A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Risdiplam (ASCEND)
A Phase 3 study testing Nusinersen in people with Spinal Muscular Atrophy, run by Biogen at 22 sites in 5 countries.
Trial summary
In this study, researchers will learn more about the use of a higher dose of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study will focus on teenagers and adults who are unable to walk on their own and who have previously taken another drug for SMA called risdiplam. Read more about this study
- Who is it for?
- Ages 15 to 50 years
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- Nusinersen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 22 sitesin 5 countries
- Study dates
- 21 Jan 2022to 24 Sep 2027
- Phase
- Phase 3
- 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 15 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation.
- Diagnosis of later-onset SMA with symptom onset at age >6 months.
- Aged ≥15 to ≤50 years at the time of informed consent
- Body weight >20 kg.
- Received oral risdiplam per the approved label or per the managed access program as follows
- Nusinersen-naive participants must have had prior treatment with risdiplam for ≥6 months before enrollment.
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- Nusinersen-experienced participants must have stopped nusinersen for ≥16 months and must have been on risdiplam for ≥12 months before enrollment.
- Able to perform the age-appropriate functional assessments in the study.
- RULM entry item A score ≥3.
- RULM total score ≥5 and ≤30 at Screening.
- Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support.
- Willing to stop risdiplam treatment.
- Willing and able to start treatment with HD nusinersen.
Who cannot join
- Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration.
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
- Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter.
- Permanent tracheostomy or permanent ventilation at Screening.
- The medical necessity, as defined by the Investigator, for noninvasive ventilation such as bilevel positive airway pressure or continuous positive airway pressure outside of regular sleep hours for any reason other than proactive SMA management, at Screening.
- History of bacterial meningitis, viral encephalitis, or hydrocephalus.
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- Ongoing medical condition that according to the Investigator would interfere with the conduct and assessments of the study. An example is a medical disability (e.g., wasting or cachexia, severe anemia, and respiratory parameters) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures.
- Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
- Treatment with an investigational drug, biological agent, or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to Screening or anytime during the study; any prior or current treatment with gene therapy for the treatment of SMA.
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
22 sites in 5 countries.
22 sites in 5 countries
United States11 sites
Rare Disease Research, LLC
Atlanta, Georgia, 30329
Boston Children's Hospital
Boston, Massachusetts, 02115-5724
Neurology Rare Disease Center
Denton, Texas, 76208
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Columbia University
New York, New York, 10032
Memorial Healthcare
Owosso, Michigan, 48867
Stanford Neuroscience Health Center
Palo Alto, California, 94304
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Barrow Neurological Institute
Phoenix, Arizona, 85013
University of Washington Medical Center
Seattle, Washington, 98195
Wake Forest University - School of Medicine - Central
Winston-Salem, North Carolina, 27157
Germany4 sites
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45122
Universitaetsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Klinikum rechts der Isar der TU Muenchen
Munich, Bavaria, 81675
Universitaetsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
Italy4 sites
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133
Fondazione Serena Onlus - Centro Clinico Nemo
Milan, 20162
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 168
Ospedale S G Battista Molinette
Torino, 10126
Japan2 sites
NHO Osaka Toneyama Medical Center
Toyonaka-shi, Osaka, 560-8552
Yokohama City University Hospital
Yokohama, Kanagawa, 236-0004
About this study
Official title: A Phase 3b Study to Evaluate Higher Dose Nusinersen (BIIB058) in Patients With Spinal Muscular Atrophy Previously Treated With Risdiplam
In this study, researchers will learn more about the use of a higher dose of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study will focus on teenagers and adults who are unable to walk on their own and who have previously taken another drug for SMA called risdiplam.
The main goal of this study is to learn about the effect of high dose (HD) nusinersen on muscle and movement ability (motor function) in SMA. The main question that researchers want to answer is:
Read more
- How do the scores of a movement test called the Revised Upper Limb Module change from the start of treatment?
The Revised Upper Limb Module is a test used to measure a participant's ability to do specific tasks that involve their shoulders, arms, wrist, elbows, and hands. It measures the changes in their abilities over time.
Researchers will also learn more about the safety of HD nusinersen. They will check participants for adverse events and changes in vital signs, heart tests, and laboratory tests including blood and urine tests.
The study will be done as follows:
- Participants will be screened to check if they can join the study.
- After screening, participants will enter the Core Treatment period.
- At the start of the Core Treatment period, they will receive 2 "loading" doses of nusinersen. These are 50 mg doses of nusinersen given 2 weeks apart.
- Afterwards, they will continue to receive "maintenance" doses of nusinersen once every 4 months. These doses will be 28 mg.
- The Core Treatment period will last about 2 years, with a follow-up visit 4 months after the last dose.
- Participants who complete the Core Treatment period will have the option to continue receiving 28 mg of nusinersen in the Long-Term Extension (LTE) period for about 2 years. There will also be a follow-up visit 4 months after the last dose.
- Nusinersen will be given through a lumbar puncture, which involves injecting the drug into the fluid around the spinal cord in the lower back.
- In total, participants will have up to 18 study visits. They will also be called by researchers after each dose of nusinersen.
- Participants will stay in the study for about 4.5 years if they complete both the Core Treatment and LTE periods.
Read the detailed description
The primary objective of this study is to evaluate motor function following treatment with HD nusinersen in participants with spinal muscular atrophy (SMA) previously treated with risdiplam.
The secondary objective of this study is to evaluate the safety and tolerability of HD nusinersen in participants with SMA previously treated with risdiplam.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- Nusinersen
- 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.
NusinersenDrug
Also called BIIB058, Spinraza
Administered as specified in the treatment arm
| Study group | Role | What they receive |
|---|---|---|
| Higher Dose Nusinersen | Experimental | All participants in the core study period, previously treated with risdiplam (nusinersen-naive participants and nusinersen-experienced participants), will receive HD nusinersen, administered as 2 loading doses of 50 milligrams (mg) each, approximately 2 weeks apart, followed by maintenance doses of 28 mg approximately every 4 months. Following the core study period, participants may be given the opportunity to receive maintenance doses of 28 mg nusinersen administered approximately every 4 months up to 2 years during the optional long-term extension (LTE) period. Receives: Drug: Nusinersen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Total Revised Upper Limb Module (RULM) Score
The RULM is being utilized to assess upper limb functional abilities of participants with SMA. This test consists of upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function.
Measured: Up to Day 855
Secondary outcomes (2)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death or in the view of the investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect, or is a medically important event.
Measured: Up to Day 1695
Number of Participants With Change in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry from Baseline
Measured: Up to Day 1695
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2021
- Study start21 Jan 2022
- Primary completion24 Sep 2027 (estimated)
- Study completion24 Sep 2027 (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 BiogenThe 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
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05067790
- Sponsor's protocol ID
- 232SM303
- Other IDs
- 2021-001294-23, 2023-505639-11, 2023
- Acronym
- ASCEND
- Status last verified
- May 2026
- First submitted
- 24 Sep 2021
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3b Study to Evaluate Higher Dose Nusinersen (BIIB058) in Patients With Spinal Muscular Atrophy Previously Treated With Risdiplam
- ClinicalTrials.gov ID
- NCT05067790
- Acronym / sponsor ID
- ASCEND / 232SM303
- Conditions
- Spinal Muscular Atrophy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 21 Jan 2022 (actual)
- Primary completion
- 24 Sep 2027 (estimated)
- Study completion
- 24 Sep 2027 (estimated)
- First posted
- 5 Oct 2021 (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.
In this study, researchers will learn more about the use of a higher dose of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study will focus on teenagers and adults who are unable to walk on their own and who have previously taken another drug for SMA called risdiplam.
The main goal of this study is to learn about the effect of high dose (HD) nusinersen on muscle and movement ability (motor function) in SMA. The main question that researchers want to answer is:
- How do the scores of a movement test called the Revised Upper Limb Module change from the start of treatment?
The Revised Upper Limb Module is a test used to measure a participant's ability to do specific tasks that involve their shoulders, arms, wrist, elbows, and hands. It measures the changes in their abilities over time.
Researchers will also learn more about the safety of HD nusinersen. They will check participants for adverse events and changes in vital signs, heart tests, and laboratory tests including blood and urine tests.
The study will be done as follows:
- Participants will be screened to check if they can join the study.
- After screening, participants will enter the Core Treatment period.
- At the start of the Core Treatment period, they will receive 2 "loading" doses of nusinersen. These are 50 mg doses of nusinersen given 2 weeks apart.
- Afterwards, they will continue to receive "maintenance" doses of nusinersen once every 4 months. These doses will be 28 mg.
- The Core Treatment period will last about 2 years, with a follow-up visit 4 months after the last dose.
- Participants who complete the Core Treatment period will have the option to continue receiving 28 mg of nusinersen in the Long-Term Extension (LTE) period for about 2 years. There will also be a follow-up visit 4 months after the last dose.
- Nusinersen will be given through a lumbar puncture, which involves injecting the drug into the fluid around the spinal cord in the lower back.
- In total, participants will have up to 18 study visits. They will also be called by researchers after each dose of nusinersen.
- Participants will stay in the study for about 4.5 years if they complete both the Core Treatment and LTE periods.
Detailed description
The primary objective of this study is to evaluate motor function following treatment with HD nusinersen in participants with spinal muscular atrophy (SMA) previously treated with risdiplam.
The secondary objective of this study is to evaluate the safety and tolerability of HD nusinersen in participants with SMA previously treated with risdiplam.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Higher Dose Nusinersen | Experimental | Drug: NusinersenAll participants in the core study period, previously treated with risdiplam (nusinersen-naive participants and nusinersen-experienced participants), will receive HD nusinersen, administered as 2 loading doses of 50 milligrams (mg) each, approximately 2 weeks apart, followed by maintenance doses of 28 mg approximately every 4 months. Following the core study period, participants may be given the opportunity to receive maintenance doses of 28 mg nusinersen administered approximately every 4 months up to 2 years during the optional long-term extension (LTE) period. |
Who may qualify
- Ages
- 15 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation.
- Diagnosis of later-onset SMA with symptom onset at age >6 months.
- Aged ≥15 to ≤50 years at the time of informed consent
- Body weight >20 kg.
- Received oral risdiplam per the approved label or per the managed access program as follows
Key exclusion criteria (10 listed)
- Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration.
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
- Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter.
- Permanent tracheostomy or permanent ventilation at Screening.
- The medical necessity, as defined by the Investigator, for noninvasive ventilation such as bilevel positive airway pressure or continuous positive airway pressure outside of regular sleep hours for any reason other than proactive SMA management, at Screening.
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 |
|---|---|---|
| NusinersenAlso: BIIB058, SpinrazaAdministered as specified in the treatment arm | Drug | Higher Dose Nusinersen |
Primary outcome
Change in Total Revised Upper Limb Module (RULM) Score
Time frame: Up to Day 855
The RULM is being utilized to assess upper limb functional abilities of participants with SMA. This test consists of upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function.
2 secondary outcomes
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to Day 1695
Number of Participants With Change in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry from Baseline
Time frame: Up to Day 1695
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 22 May 2026.
- Disclaimer: Residents in the United States may click here to find out more about participation in this trial.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Related trials for Spinal Muscular Atrophy
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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.
Medical Director study director
Biogen
22 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nusinersen in people with Spinal Muscular Atrophy, run by Biogen at 22 sites in 5 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 13 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: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Germany, Italy, Japan, Hungary. 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?
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?
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?
Change in Total Revised Upper Limb Module (RULM) Score (time frame: Up to Day 855). 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 22 May 2026; AzTrials last refreshed its copy on 31 Oct 2026.