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)

Study Overview
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Brief Summary
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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.

Detailed Description
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This study is an extension study of NCT03626012.

Official Title
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An Extension Study to Assess the Long-Term Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB078 Administered to Previously Treated Adults With C9ORF72-Associated Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: BIIB078


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: BIIB078 First Dosage<br>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. | Drug: BIIB078<br>* Administered as specified in the treatment arm.<br>|
| Experimental: Cohort B: BIIB078 Second Dosage<br>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. | Drug: BIIB078<br>* Administered as specified in the treatment arm.<br>|
| Experimental: Cohort C: BIIB078 Third Dosage<br>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. | Drug: BIIB078<br>* Administered as specified in the treatment arm.<br>|
| Experimental: Possible Cohort D: BIIB078 Fourth Dosage<br>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. | Drug: BIIB078<br>* Administered as specified in the treatment arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | 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. | Baseline up to Day 785 | 
| Number of Participants with Serious Adverse Events (SAEs) | 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. | Screening up to Day 785 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |