There was no evidence of benefit across efficacy endpoints in the randomized trial, 245AS101. Accordingly, Biogen has made the difficult decision to discontinue the BIIB078 program including this open label extension trial, 245AS102.

The primary objective is to evaluate the long-term safety and tolerability of BIIB078 in participants with chromosome 9 open reading frame 72-amyotrophic lateral sclerosis (C9ORF72-ALS).

The secondary objective is to evaluate the pharmacokinectic (PK) of BIIB078 in participants with C9ORF72-ALS.

This study is an extension study of NCT03626012.

Key Inclusion Criteria:

• 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.
• 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.

Key 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.
• Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter.
• 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.
• 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.

Note: Other protocol-specific inclusion/exclusion criteria may apply.

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

During the blinded loading period, the following individuals will be masked:

• Investigator
• Study staff
• Participants

After the loading period has been completed, subsequent doses will be open-label.