Amyotrophic lateral sclerosis neurodegenerative disease
Conditions
Interventions
Subjects within each of the 4 cohorts will be randomized in a 3:1 (active:
placebo) ratio overall to receive BIIB078 or placebo.
The first 2 dose levels will be administered to approximately 8 subje
Sponsors
Biogen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Ability of the subject or his/her legally authorized representative (e.g., spouse) to understand the purpose and risks of the study, and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local subject privacy regulations. 2. Age >= 18 years old at the time of informed consent. 3. All subjects of childbearing potential must agree to practice highly effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment. In addition, subjects should not donate sperm or eggs for the duration of the study and for at least 5 months after their last dose of study treatment. 4. Must meet the possible, laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria and have documentation of a clinical genetic test demonstrating the presence of a pathogenic mutation in C9ORF72. 5. Slow vital capacity (SVC) >= 50% of predicted value as adjusted for sex, age, and height (from the sitting position). 6. Subjects taking concomitant riluzole at study entry must be on a stable dose for >= 30 days prior to the first dose of study treatment (Day 1). Subjects 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. 7. Subjects 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). Subjects taking concomitant edaravone must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study. Edaravone may not be administered on dosing days of this study. 8. ALS Cognitive Behavioral Screen (ALS-CBS) score >= 11 for the cognitive portion; >= 33 for the behavioral portion. 9. Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry, as determined by the Investigator. 10. Screening values of coagulation parameters including platelet count, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (APTT) should be within normal ranges. Coagulation tests may be repeated once at the local laboratory if, in the opinion of the Investigator, values of the initial tests are out of range but not clinically significant. Subjects with nonclinically significant and stable out-of-range values may be eligible to enroll in the study at the discretion of the Investigator, and after a consultation with the Sponsor. 11. Has an informant/caregiver who, in the Investigator*s judgment, has frequent and sufficient contact with the subject as to be able to provide accurate information about the subject*s cognitive and functional abilities at Screening. An informant/caregiver should be available at Screening, and the participation of the informant/caregiver for the duration of the study is encouraged.
Exclusion criteria
Exclusion criteria: Medical History 1. History of drug abuse or alcoholism 450 ms for males and >470 ms for females. 12. Alanine aminotransferase , aspartate aminotransferase , or total bilirubin levels >= 2 times the upper limit of normal. Patients with previously established Gilbert*s syndrome and elevated levels of bilirubin consistent with such syndrome are allowed in the study. Infections 13. History of or positive test result at Screening for human immunodeficiency virus. The requirement for testing at Screening may be omitted if it is not permitted by local regulations. 14. History of, or positive test result at Screening for, hepatitis C virus antibody. 15. Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Subjects with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive hepatitis B surface antibody immunoglobulin G, and positive HBcAb) or vaccination (defined as positive hepatitis B surface antibody [HBsAb]) are eligible to participate in the study. 16. Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period. Medications 17. Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs) or biological agent within 1 month of Screening or 5 half-lives of study agent, whichever is longer. 18. Treatment with antiplatelet or anticoagulant therapy <= 14 days before Screening (with the excepti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse and serious adverse events. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Serum BIIB078 concentration - Serum PK parameters: - Area under the concentration-time curve (AUC) from time 0 to infinity (AUC*) - AUC from time 0 to time of the last measurable concentration (AUClast) - Maximum observed concentration (Cmax) - Time to reach Cmax (Tmax) - Terminal elimination half-life (t*) | — |
Countries
Netherlands
Outcome results
None listed