The trial is taking place at:

University of Wisconsin | Department of Ophthalmology and Visual Sciences - Clinical Eye Research Unit

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A Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Previously Treated With Risdiplam (ASCEND)

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Status and phase

Phase 3


Spinal Muscular Atrophy


Drug: Nusinersen

Study type


Funder types



2021-001294-23 (EudraCT Number)
2023-505639-11 (Other Identifier)

Details and patient eligibility


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.


45 estimated patients




15 to 50 years old


No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

  • 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.
  • 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.

Key Exclusion Criteria:

  • 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.
  • 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 design

Primary purpose




Interventional model

Single Group Assignment


None (Open label)

45 participants in 1 patient group

Higher Dose Nusinersen
Experimental group
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.
Drug: Nusinersen

Trial contacts and locations



Central trial contact

Global Biogen Clinical Trial Center; US Biogen Clinical Trial Center

Data sourced from

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