Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy

Prior treatment

• Hospitalization for surgery, pulmonary event, or nutritional support within 2 months prior to Screening or planned within 12 months after the participant's first dose
  • Part A:
• Treatment with an investigational drug given for the treatment of SMA, 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 any survival motor neuron-2 gene (SMN2)-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation
  • Part B:
• Treatment with an investigational drug including but not limited to the treatment of SMA, 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 any SMN2-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation
• Concurrent or previous participation and/or administration of nusinersen in another clinical study
• Concomitant or previous administration of any SMN2-splicing modifier (excluding nusinersen) or gene therapy, either in a clinical study or as part of medical care.
• Concurrent or previous participation in any interventional investigational study for any other drug or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to Screening
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Other illness

• Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening period
• Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for \> 6 hours during a 24-hour period, at Screening

Age

• Participants with SMA symptom onset \> 6 months (\> 180 days) of age (later onset):
  • Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for \> 6 hours during a 24-hour period, at Screening
  • Medical necessity for a gastric feeding tube
• Participants with SMA symptom onset ≤ 6 months (≤ 180 days) of age (infantile onset): Signs or symptoms of SMA present at birth or within the first week after birth
  • Part C:

Other

• Part A, B and C:
• Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or of an implanted central nervous system (CNS) catheter
• Medical necessity for a gastric feeding tube

• Part A, B and C:
• \- Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound heterozygote)
• Part A:
• Onset of clinical signs and symptoms consistent with SMA at \> 6 months (\> 180 days) of age (i.e., later-onset SMA)
• Age 2 to ≤ 15 years, inclusive, at the time of informed consent
  • Part B:
• Participants with SMA symptom onset ≤ 6 months (≤ 180 days) of age (infantile onset) should have age \> 1 week to ≤ 7 months (≤ 210 days) at the time of informed consent
• Participants with SMA symptom onset \> 6 months (\> 180 days) of age (later onset):
  • Age 2 to \< 10 years at the time of informed consent
  • Can sit independently but has never had the ability to walk independently
  • HFMSE score ≥ 10 and ≤ 54 at Screening
  • Part C:
  • \- Currently on nusinersen treatment at the time of Screening, with the first dose being at least 1 year prior to Screening
  • Part C Cohort 1:
  • \- Participants of any age (individuals ≥18 years of age at Screening must be ambulatory)
  • Part C Cohort 2:
• Participants ≥18 years of age at Screening (can be ambulatory or nonambulatory)
• HFMSE total score ≥4 points at Screening
• RULM entry item A score ≥3 points at Screening