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 compoundheterozygote)

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 dosebeing at least 1 year prior to Screening

Part C Cohort 1:

• Participants of any age (individuals ≥18 years of age at Screening must beambulatory)

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 systemicantiviral or antimicrobial therapy at any time during the Screening period

• Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or ofan implanted central nervous system (CNS) catheter

• Hospitalization for surgery, pulmonary event, or nutritional support within 2 monthsprior to Screening or planned within 12 months after the participant's first dose

Part A:

• Respiratory insufficiency, defined by the medical necessity for invasive ornoninvasive 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, biologicalagent, 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 withany survival motor neuron-2 gene (SMN2)-splicing modifier or gene therapy; or priorantisense oligonucleotide treatment, or cell transplantation

Part B:

• Treatment with an investigational drug including but not limited to the treatment ofSMA, 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 orcurrent treatment with any SMN2-splicing modifier or gene therapy; or priorantisense 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 ornoninvasive 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 (infantileonset): Signs or symptoms of SMA present at birth or within the first week afterbirth

Part C:

• Concurrent or previous participation and/or administration of nusinersen in anotherclinical study

• Concomitant or previous administration of any SMN2-splicing modifier (excludingnusinersen) or gene therapy, either in a clinical study or as part of medical care.

• Concurrent or previous participation in any interventional investigational study forany other drug or device within 30 days or 5 half-lives of the agent, whichever islonger, prior to Screening

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.