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: June 28, 2021
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: May 8, 2019
• First Posted Date: May 10, 2019
• Last Update Posted Date: June 28, 2021
• Actual Study Start Date: May 30, 2019
• Actual Primary Completion Date: June 21, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 8, 2019)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 8, 2019)

• 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.
• 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.
• Maximum Observed Concentration (Cmax) of BIIB100 [ Time Frame: Day 1 (pre-dose) up to Day 3 ]
  BIIB100 will be measured in the plasma.
• Time to Reach Cmax (Tmax) of BIIB100 [ Time Frame: Day 1 (pre-dose) up to Day 3 ]
  BIIB100 will be measured in the plasma.
• 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.
• Apparent Clearance (CL/F) of BIIB100 [ Time Frame: Day 1 (pre-dose) up to Day 3 ]
  BIIB100 will be measured in the plasma.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adults With Amyotrophic Lateral Sclerosis
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis

Intervention

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

Study Arms

• Experimental: Cohort 1: BIIB100 Dose 1
  Participants will receive single oral dose of BIIB100 on Day 1.
  Intervention: Drug: BIIB100
• Experimental: Cohort 2: BIIB100 Dose 2
  Participants will receive single oral dose of BIIB100 on Day 1.
  Intervention: Drug: BIIB100
• Experimental: Cohort 3: BIIB100 Dose 3
  Participants will receive single oral dose of BIIB100 on Day 1.
  Intervention: Drug: BIIB100
• Experimental: Cohort 4: BIIB100 Dose 4
  Participants will receive single oral dose of BIIB100 on Day 1.
  Intervention: Drug: BIIB100
• Experimental: Cohort 5: BIIB100 Dose 5
  Participants will receive single oral dose of BIIB100 on Day 1.
  Intervention: Drug: BIIB100
• Experimental: Cohort 6: BIIB100 Dose 6
  Participants will receive single oral dose of BIIB100 on Day 1.
  Intervention: Drug: BIIB100
• Placebo Comparator: Cohort 1-6: Matching Placebo
  Participants will receive single oral dose of matching placebo on Day 1.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 25, 2021): 49
• Original Estimated Enrollment (submitted: May 8, 2019): 40
• Actual Study Completion Date: June 21, 2021
• Actual Primary Completion Date: June 21, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03945279
• Other Study ID Numbers: 261AS101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

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

• Current Responsible Party: Biogen
• Original Responsible Party: Same as current
• Current Study Sponsor: Biogen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: June 2021