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)

NCT04288856 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 245AS1022019-004798-14
• Study Type: interventional
• Target: 75
• Locations: 5 countries
• Sites: 21

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (4)

Cohort A: BIIB078 First Dosage

EXPERIMENTAL

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

Cohort B: BIIB078 Second Dosage

EXPERIMENTAL

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

Cohort C: BIIB078 Third Dosage

EXPERIMENTAL

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

Possible Cohort D: BIIB078 Fourth Dosage

EXPERIMENTAL

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

Interventions

BIIB078 DRUG

Administered as specified in the treatment arm.

Cohort A: BIIB078 First Dosage; Cohort B: BIIB078 Second Dosage; Cohort C: BIIB078 Third Dosage; Possible Cohort D: BIIB078 Fourth Dosage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (21)

Research Site

La Jolla, California, 92037, United States

Location

Research Site

Los Angeles, California, 90048, United States

Location

Research Site

Palo Alto, California, 94304, United States

Location

Research Site

Jacksonville, Florida, 32224, United States

Location

Research Site

Miami, Florida, 33136, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Baltimore, Maryland, 21287, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Lincoln, Nebraska, 68506, United States

Location

Research Site

New York, New York, 10032, United States

Location

Research Site

Knoxville, Tennessee, 37920, United States

Location

Research Site

Calgary, Alberta, T2N 1N4, Canada

Location

Research Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Research Site

Toronto, Ontario, M4N 3M5, Canada

Location

Research Site

Montreal, Quebec, H3A 2B4, Canada

Location

Research Site

Utrecht, 3508 GA, Netherlands

Location

Research Site

Sankt Gallen, 9007, Switzerland

Location

Research Site

London, Greater London, NW1 2PG, United Kingdom

Location

Research Site

London, Greater London, SE5 9RS, United Kingdom

Location

Research Site

Sheffield, South Yorkshire, S10 2HQ, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2020
• First Posted: February 28, 2020
• Study Start: April 28, 2020
• Primary Completion: May 3, 2022
• Study Completion: May 3, 2022
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

CH (1); NL (1); US (12); GB (3); CA (4)