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

• ClinicalTrials.gov Identifier: NCT03945279
• Recruitment Status: Completed
• First Posted: May 10, 2019
• Last Update Posted: April 18, 2023
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: BIIB100; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 30, 2019
• Actual Primary Completion Date: June 21, 2021
• Actual Study Completion Date: June 21, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Screening (Day -28 ) up to Day 15 ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Barrow Neurological Institute

Phoenix, Arizona, United States, 85013

United States, California

University of California San Diego Medical Center

San Diego, California, United States, 92121

United States, Florida

Mayo Clinic Hospital

Jacksonville, Florida, United States, 32224

University of South Florida

Tampa, Florida, United States, 33612

United States, Maryland

Johns Hopkins University, Dept of Neurology

Baltimore, Maryland, United States, 21205

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 21219

United States, Missouri

Research Site

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Research Site

Lincoln, Nebraska, United States, 68506

United States, Tennessee

Alliance for Multispecialty Research NOCCR/VRG

Knoxville, Tennessee, United States, 37920

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT03945279
• Other Study ID Numbers: 261AS101
• First Posted: May 10, 2019
• Last Update Posted: April 18, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases