A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adults With Amyotrophic Lateral Sclerosis

A Phase 1, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adult Participants With Amyotrophic Lateral Sclerosis

The primary objective of this study is to evaluate the safety, tolerability of single-ascending doses of BIIB100 in adults with amyotrophic lateral sclerosis (ALS). The secondary objective of the study is to characterize the pharmacokinetic profile of BIIB100.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: BIIB100

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
  • California
    • San Diego, California, United States, 92121
      • University of California San Diego Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Hospital
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University, Dept of Neurology
  • Massachusetts
    • Boston, Massachusetts, United States, 21219
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research NOCCR/VRG

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Must meet the laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria.
• Participants taking concomitant riluzole at study entry must be on a stable dose for greater than or equals to (>=) 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).
• Adequate respiratory function as indicated by slow vital capacity (SVC) >= 65% of predicted value as adjusted for sex, age, and height (from the sitting position).

Key Exclusion Criteria:

• Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that would, in the opinion of the Investigator, interfere with the conduct or assessments of the study.
• Significant cognitive impairment or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression less than or equals to (<=) 90 days of Screening, which in the opinion of the Investigator would interfere with the study procedures.
• Treatment with drugs that are transported by Breast Cancer Resistance Protein (BCRP) and P-glycoprotein (P-gp) including, but not limited to, rosuvastatin, sulfasalazine, dabigatran, digoxin and fexofenadine.
• Current enrollment or plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days or 5 half-lives of the agent, whichever is longer, prior to the Baseline Visit (pre-dose on Day 1). Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator and after consultation with the Sponsor.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: BIIB100 Dose 1; Participants will receive single oral dose of BIIB100 on Day 1.	Drug: BIIB100; Administered as specified in the treatment arm.
Experimental: Cohort 2: BIIB100 Dose 2; Participants will receive single oral dose of BIIB100 on Day 1.	Drug: BIIB100; Administered as specified in the treatment arm.
Experimental: Cohort 3: BIIB100 Dose 3; Participants will receive single oral dose of BIIB100 on Day 1.	Drug: BIIB100; Administered as specified in the treatment arm.
Experimental: Cohort 4: BIIB100 Dose 4; Participants will receive single oral dose of BIIB100 on Day 1.	Drug: BIIB100; Administered as specified in the treatment arm.
Experimental: Cohort 5: BIIB100 Dose 5; Participants will receive single oral dose of BIIB100 on Day 1.	Drug: BIIB100; Administered as specified in the treatment arm.
Experimental: Cohort 6: BIIB100 Dose 6; Participants will receive single oral dose of BIIB100 on Day 1.	Drug: BIIB100; Administered as specified in the treatment arm.
Placebo Comparator: Cohort 1-6: Matching Placebo; Participants will receive single oral dose of matching placebo on Day 1.	Drug: Placebo; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, or is a medically important event.	Screening (Day -28 ) up to Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Maximum Observed Concentration (Cmax) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Time to Reach Cmax (Tmax) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Terminal Elimination Half-life (t1/2) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Apparent Clearance (CL/F) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Apparent Volume of Distribution During the Terminal Elimination (Vz/F) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Actual): June 21, 2021
• Study Completion (Actual): June 21, 2021

Study Registration Dates

• First Submitted: May 8, 2019
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (Actual): May 10, 2019

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; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 261AS101

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
• product manufactured in and exported from the U.S.: No