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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03945279
• Other study ID #: 261AS101
• Status: Completed
• Phase: Phase 1
• Start date: May 30, 2019
• Est. completion date: June 21, 2021

Study information

• Verified date: April 2023
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: June 21, 2021
• Est. primary completion date: June 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• BIIB100
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
United States	Johns Hopkins University, Dept of Neurology	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Mayo Clinic Hospital	Jacksonville	Florida
United States	Alliance for Multispecialty Research NOCCR/VRG	Knoxville	Tennessee
United States	Research Site	Lincoln	Nebraska
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Research Site	Saint Louis	Missouri
United States	University of California San Diego Medical Center	San Diego	California
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Maximum Observed Concentration (Cmax) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Secondary	Time to Reach Cmax (Tmax) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Secondary	Terminal Elimination Half-life (t1/2) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Secondary	Apparent Clearance (CL/F) of BIIB100	BIIB100 will be measured in the plasma.	Day 1 (pre-dose) up to Day 3
Secondary	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