Inclusion Criteria:

• The participant and his or her legally authorized representative (e.g., spouse) must have the ability to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information in accordance with national and local participant privacy regulations; or, in the event of the participant’s physical incapacity to sign, to confirm that understanding and consent orally to a legally authorized representative for the express purpose of having said informed consent and authorization signed on his or her behalf.
• Participants must have completed study NCT03626012 through the first follow-up clinic visit that follows the final dosing visit without missing more than 1 dose of study treatment.
• All women of childbearing potential and all men must practice highly effective contraception during the study and for 5 months after their last dose of study treatment. In addition, participants should not donate sperm or eggs for the duration of the study and for at least 5 months after their last dose of study treatment.
• Participants taking concomitant riluzole at study entry must be on a stable dose for ≥ 30 days prior to the first dose of study treatment (Day 1). Participants taking concomitant riluzole must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that riluzole should be discontinued for medical reasons, in which case it may not be restarted during the study.
• Participants taking concomitant edaravone at study entry must be on a stable dose for ≥ 60 days prior to the first dose of study treatment (Day 1). Participants taking concomitant edaravone must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study. Edaravone may not be administered on dosing days of this study.
• Participants must be medically able to undergo the study procedures and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
• Screening values of platelet count and coagulation parameters including international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) should be within normal ranges. Coagulation tests may be done at a local laboratory in order to reduce patient burden. Platelet count and coagulation tests may be repeated once at the local laboratory if, in the opinion of the Investigator, values of the initial tests are out of range but not clinically significant. Participants with nonclinically significant and stable out-of-range values may be eligible to enroll in the study with approval at the discretion of the Investigator and after a consultation with the Sponsor.

Exclusion Criteria:

• History of drug abuse or alcoholism ≤ 6 months before study enrollment that would limit participation in the study, as determined by the Investigator.
• Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that would, in the opinion of the Investigator, interfere with the conduct or assessments of the study.
• Significant cognitive impairment or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression ≤ 90 days of Screening, that would, in the opinion of the Investigator, interfere with the study procedures.
• History of allergies to substances that will be used for the LP (e.g., anesthetics, if used per institutional practice).
• Presence of risk of bleeding that could place a participant at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, von Willebrand’s disease, or liver disease).
• Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter.
• Clinically significant abnormalities in hematology or blood chemistry parameters, as determined by the Investigator, which would render the participant unsuitable for enrollment.
• Clinically significant, as determined by the Investigator, 12-lead electrocardiogram (ECG) abnormalities, including corrected QT interval using Fridericia’s correction method of > 450 ms for males and > 460 ms for females.
• Alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels ≥ 2 times the upper limit of normal. Participants with previously established Gilbert’s syndrome and elevated levels of bilirubin consistent with such syndrome are allowed in the study.
• History of systemic hypersensitivity reaction to BIIB078, the excipients contained in the formulation and, if appropriate, any diagnostic agents to be administered during the study.
• History of or positive test result at Screening for human immunodeficiency virus. The requirement for testing at Screening may be omitted if it is not permitted by local regulations.
• Current hepatitis C infection (defined as positive hepatitis C virus [HCV] antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study (United States Centers for Disease Control and Prevention).
• Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [anti-HBc]). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive hepatitis B surface antibody [anti-HBs]) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.
• Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy, or any other ongoing medical condition during the screening period that, according to the Investigator, would interfere with the conduct or assessments of the study.
• Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs) or biological agent within 1 month of Screening or 5 half-lives of study agent, whichever is longer.
• Treatment with antiplatelet or anticoagulant therapy that cannot safely be interrupted for LP according to local standard of care and/or institutional guidelines, in the opinion of the Investigator or Prescriber.
• Pregnant or currently breastfeeding and those intending to become pregnant during the study.
• Concurrent enrollment in any other interventional study. Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator and after consultation with the Sponsor.
• Inability to comply with study requirements.
• Other unspecified reasons that, in the opinion of the Investigator or the Sponsor, make the participant unsuitable for enrollment.