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

NCT03945279 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 261AS101
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of BIIB100

  Day 1 (pre-dose) up to Day 3

• Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of BIIB100

  Day 1 (pre-dose) up to Day 3

• Maximum Observed Concentration (Cmax) of BIIB100

  Day 1 (pre-dose) up to Day 3

• Time to Reach Cmax (Tmax) of BIIB100

  Day 1 (pre-dose) up to Day 3

• Terminal Elimination Half-life (t1/2) of BIIB100

  Day 1 (pre-dose) up to Day 3

Study Arms (7)

Cohort 1: BIIB100 Dose 1

EXPERIMENTAL

Participants will receive single oral dose of BIIB100 on Day 1.

Drug: BIIB100

Cohort 2: BIIB100 Dose 2

EXPERIMENTAL

Participants will receive single oral dose of BIIB100 on Day 1.

Drug: BIIB100

Cohort 3: BIIB100 Dose 3

EXPERIMENTAL

Participants will receive single oral dose of BIIB100 on Day 1.

Drug: BIIB100

Cohort 4: BIIB100 Dose 4

EXPERIMENTAL

Participants will receive single oral dose of BIIB100 on Day 1.

Drug: BIIB100

Cohort 5: BIIB100 Dose 5

EXPERIMENTAL

Participants will receive single oral dose of BIIB100 on Day 1.

Drug: BIIB100

Cohort 6: BIIB100 Dose 6

EXPERIMENTAL

Participants will receive single oral dose of BIIB100 on Day 1.

Drug: BIIB100

Cohort 1-6: Matching Placebo

PLACEBO COMPARATOR

Participants will receive single oral dose of matching placebo on Day 1.

Drug: Placebo

Interventions

BIIB100 DRUG

Administered as specified in the treatment arm.

Cohort 1: BIIB100 Dose 1; Cohort 2: BIIB100 Dose 2; Cohort 3: BIIB100 Dose 3; Cohort 4: BIIB100 Dose 4; Cohort 5: BIIB100 Dose 5; Cohort 6: BIIB100 Dose 6

Placebo DRUG

Administered as specified in the treatment arm.

Cohort 1-6: Matching Placebo

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (9)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

University of California San Diego Medical Center

San Diego, California, 92121, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Johns Hopkins University, Dept of Neurology

Baltimore, Maryland, 21205, United States

Location

Research Site

Boston, Massachusetts, 21219, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Lincoln, Nebraska, 68506, United States

Location

Alliance for Multispecialty Research NOCCR/VRG

Knoxville, Tennessee, 37920, United States

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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 10, 2019
• Study Start: May 30, 2019
• Primary Completion: June 21, 2021
• Study Completion: June 21, 2021
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

US (9)