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)

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

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.

Study Overview

• Status: Terminated
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: BIIB078

Detailed Description

This study is an extension study of NCT03626012.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • Research Site
    • Edmonton, Alberta, Canada, T6G 2B7
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Research Site
• Netherlands
  • Utrecht, Netherlands, 3508 GA
    • Research Site
• Switzerland
  • St. Gallen, Switzerland, 9007
    • Research Site
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
      • Research Site
    • London, Greater London, United Kingdom, NW1 2PG
      • Research Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2HQ
      • Research Site
• United States
  • California
    • La Jolla, California, United States, 92037
      • Research Site
    • Los Angeles, California, United States, 90048
      • Research Site
    • Palo Alto, California, United States, 94304
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Research Site
    • Miami, Florida, United States, 33136
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Research Site
  • New York
    • New York, New York, United States, 10032
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: BIIB078 First Dosage; 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; Administered as specified in the treatment arm.
Experimental: Cohort B: BIIB078 Second Dosage; 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; Administered as specified in the treatment arm.
Experimental: Cohort C: BIIB078 Third Dosage; 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; Administered as specified in the treatment arm.
Experimental: Possible Cohort D: BIIB078 Fourth Dosage; 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; Administered as specified in the treatment arm.

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2020
• Primary Completion (Actual): May 3, 2022
• Study Completion (Actual): May 3, 2022

Study Registration Dates

• First Submitted: February 26, 2020
• First Submitted That Met QC Criteria: February 26, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Disease Progression; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 245AS102; 2019-004798-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No