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

Key Inclusion Criteria:

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

Key Exclusion Criteria:

Part A, B and C:

   - 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 cerebrospinal fluid (CSF) or of an
   implanted central nervous system (CNS) catheter

   - 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:

   - 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

   - 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

   - 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:

   - 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.