A Study to Learn About the Safety of BIIB115 Injections and How BIIB115 is Processed in the Bodies of Healthy Adult Male Volunteers and of Pediatric Participants With Spinal Muscular Atrophy Who Previously Took Onasemnogene Abeparvovec

The primary objective of the study is to assess the safety and tolerability of BIIB115 administered via intrathecal (IT) bolus injection to healthy participants in Part A, pediatric participants with spinal muscular atrophy who have previously received onasemnogene abeparvovec in Part B, and to participants who complete Part B in Part B LTE. The secondary objectives of the study is to evaluate the pharmacokinetics (PK) of BIIB115 in Parts A, B, and B LTE.

Key Inclusion Criteria:

Part A:

• Male healthy participants aged 18 to 55 years, inclusive
• Have a body mass index of 18 to 30 kilograms per meter square (kg/m^2), inclusive
• Must be in good health as determined by the investigator, based on medical history and screening evaluations

Part B:

• Age 0.5 to 12 years old, inclusive, at the time of informed consent
• Weight ≥7 kg at the time of informed consent
• Genetic diagnosis of SMA (5q SMA homozygous survival motor neuron 1 (SMN1) gene deletion or mutation or compound heterozygous mutation)
• Survival motor neuron 2 (SMN2) copy number ≥1
• Must have received intravenous (IV) onasemnogene abeparvovec per the approved label or per guidelines including the steroid regimen and monitoring specified therein
• Treatment with onasemnogene abeparvovec ≥180 days prior to first BIIB115 dose
• Potential for improvement due to suboptimal clinical status secondary to SMA, as determined by the Investigator

Part B LTE

• Completion of the assessments in Part B
• Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures (as assessed by the Investigator and either anesthesiologist or pulmonologist).

Key Exclusion Criteria:

Part A:

• Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from multiple lumbar puncture (LP) procedures required for dosing and CSF collection, per the investigator discretion
• History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator
• Chronic, recurrent, or serious infection, as determined by the investigator, within 90 days prior to screening or between screening and Day -1
• Current enrollment or a plan to enroll in any interventional clinical study of a drug, biologic, or device, in which an investigational treatment or approved therapy for investigational use is administered within 3 months (or 5 half-lives of the agent, whichever is longer) prior to randomization

Part B:

• Severe or serious AEs related to onasemnogene abeparvovec therapy that are ongoing during Screening
• Interval of <180 days between onasemnogene abeparvovec therapy and first BIIB115 dose
• Ongoing steroid treatment following onasemnogene abeparvovec at time of screening
• History of drug induced liver injury or liver failure per Hy's law definition
• History of thrombotic micrangiopathy
• Treatment with any SMN2-splicing modifier (nusinersen or risdiplam) after receiving onasemnogene abeparvovec. Treatment with nusinersen <12 months from the first dose of BIIB115.
• Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from the LP procedures, CSF circulation, or safety assessments, including a history of hydrocephalus or implanted shunt for CSF drainage.
• Permanent ventilation, defined as tracheostomy or ≥16 hours ventilation /day continuously for >21 days in the absence of an acute reversible event

Part B LTE:

• Any new condition or worsening of an existing condition that, according to the Investigator, would make the participant unsuitable for inclusion, could interfere with the assessment of safety, or would compromise the ability of the participant to undergo study procedures.
• Clinically significant abnormalities in hematology, blood chemistry parameters, or electrocardiograms (ECGs) prior to first LTE visit that would make the participant unsuitable for inclusion as assessed by the Investigator.
• Treatment with an approved SMN2-splicing modifier (nusinersen or risdiplam).

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