Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB078 Administered to Previously Treated Adults C9ORF72-Associated Amyotrophic Lateral Sclerosis (ALS)

Recruitment & Eligibility

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.

Study & Design

Arm && Interventions

Group	Intervention	Description
Cohort C: BIIB078 Third Dosage	BIIB078	BIIB078 will be administered as 3 doses during the loading period, approximately 2 weeks apart, and maintenance doses, approximately 4 weeks apart, via IT infusion.
Possible Cohort D: BIIB078 Fourth Dosage	BIIB078	BIIB078 will be administered as 3 doses during the loading period, approximately 2 weeks apart, and maintenance doses, approximately 4 weeks apart, via IT infusion.
Cohort B: BIIB078 Second Dosage	BIIB078	BIIB078 will be administered as 3 doses during the loading period, approximately 2 weeks apart, and maintenance doses, approximately 4 weeks apart, via IT infusion.
Cohort A: BIIB078 First Dosage	BIIB078	BIIB078 will be administered as 3 doses during the loading period, approximately 2 weeks apart, and maintenance doses, approximately 4 weeks apart, via IT infusion.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events (AEs)	Baseline up to Day 785	AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Number of Participants with Serious Adverse Events (SAEs)	Screening up to Day 785	An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

Secondary Outcome Measures

Name	Time	Method
Serum concentration of BIIB078	Baseline and at multiple time points up to Day 729
Cerebrospinal Fluid (CSF) concentration of BIIB078	Baseline and at multiple time points up to Day 729

Recruitment & Eligibility