Amyotrophic lateral sclerosis (ALS) neurodegenerative disease
Conditions
Interventions
Participants with ALS:
• Cohort A: BIIB105 5 mg (6 participants) or placebo (2 participants)
• Cohort B: BIIB105 20 mg (6 participants) or placebo (2 participants)
• Cohort C1: BIIB105 60 mg (9 partic
Sponsors
Biogen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: Part 1: - Ability of the participant to understand the purpose and risks of the study and indicate informed consent, and the ability of the participant or the participant's legally authorized representative to provide signed and dated informed consent and authorization to use protected health information in accordance with national and local privacy regulations. - All women of childbearing potential and all men must ensure that highly effective contraception is used during the study and for at least 6 months for female participants and 8 months for male participants after their last dose of study treatment. - No known presence or family history of mutations in the the dismutase 1 (SOD1) or fused in sarcoma (FUS) genes. - Participants in Cohorts A, B, C1 and D1, must meet the laboratory supported probable, probable, or definite criteria for diagnosing ALS according to the World Federati of Neurology El Escorial criteria (revised according to the Airlie House Conference 1998 [Brooks 2000]). Participants in Cohort C2 and D2, must meet any of the prior conditions, but may also only meet clinically possible criteria for diagnosing ALS, or exhibit weakness attributable to ALS in the presence of ataxin-2 protein (ATXN2) intermediate repeats. - In participants in Cohorts C2 and D2, confirmed intermediate cytosineadenine- uanine/cytosine-adenine-adenine (CAG/CAA) repeat expansion in the ataxin-2 gene or RNA (ATXN2) gene as defined by at least 1 allele carrying 30 to 33 CAG/CAA repeats. - Slow vital capacity (SVC) criteria: - In participants in Cohorts A, B, C1, and D1, SVC >=60% of predicted value as adjusted for sex, age, and height (from the sitting position). - In participants in Cohorts C2 and D2, SVC >=50% of predicted value as adjusted for sex, age, and height (from the sitting position). - If taking riluzole, participant must be on a stable dose for >=30 days prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that it 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 (Day1). Participants 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. - 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. - Has an informant/caregiver who, in the Investigator's judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities at screening. Part 2: - Ability of the participant to understand the purpose and risks of the study and indicate informed consent, and the ability of the participant or the participant's legally authorized representative to provide signed and dated <br
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: Part 1 : - History or positive test result at Screening for human immunodeficiency virus (HIV). - Current hepatitis C infection. - Current hepatitis B infection. - History of alcohol or substance abuse =8% during Screening. - In participants in Cohorts A, B, and C1, prescreening ALSFRS-R slope >- 0.4 points/month, where prescreening ALSFRS-R slope is defined as: (ALSFRS-R score at Screening - 48) / (months from date of symptom onset to date of Screening). This criterion is not applicable for Cohorts C2, D1, and D2. - Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs) or biological agent within 1 month or 5 half-lives of study agent, whichever is longer, before Screening. -Treatment with an approved disease-modifying therapy for ALS other than riluzole or edaravone within 1 month or 5 half-lives of therapy, whichever is longer, before completion of screening. - Treatment with an antiplatelet or anticoagulant therapy that cannot safely be interrupted for lumbar puncture (LP) according to local standard of care and/or institutional guidelines, in the opinion of the Investigator or Prescriber. - Female participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study. Part 2: - History or positive test result at Screening for HIV. If participants from Cohorts D1 and D2 who would seamlessly roll from Part 1 into Part 2 test positive for HIV during screening for Part 2 but are clinically symptomatic, they may enroll in Part 2 at the discretion of the Investigator. -Current hepatitis C infection. If participants from Cohorts D1 and D2 who would seamlessly roll from Part 1 into Part 2 test positive for hepatitis C during screening for Part 2 but are clinically asymptomatic, they may enroll in Part 2 at the discretion of the Investigator. - Current hepatitis B infection. If participants from Cohorts D1 and D2 who would seamlessly roll from Part 1 into Part 2 test positive for hepatitis B during screening for Part 2 but are clinically asymptomatic, they may enroll in Part 2 at the discretion of the Investigator. - History of alcohol or substance abuse = 8% during Screening. -Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs; exc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Part 2: Number of Participants with AEs and SAEs | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1:The secondary objectives are to assess the pharmacokinetic (PK) profile in serum and cerebrospinal fluid (CSF), and to evaluate the biomarker effect of BIIB105 in participants with ALS or polyQ-ALS. Parts 1 and 2:The secondary objectives are to assess the long-term PK profile of BIIB105 in serum and CSF of participants with ALS or polyQALS; to evaluate the long-term biomarker effect of BIIB105 in participants with ALS or polyQ-ALS, and, where relevant, to assess the impact of earlier initiation of BIIB105 (i.e., at start of Part 1) compared with delayed initiation of BIIB105 (i.e., at start of Part 2) on biomarkers; to evaluate the long-term effect of BIIB105 on measures of clinical function and, where relevant to assess the impact of earlier initiation of BIIB105 (i.e., at start of Part 1) compared with delayed initiation of BIIB105 (i.e., at start of Part 2) on measures of clinical function. Part 1: 1. Serum Concentration of BIIB105 2. CSF Concentrations of BIIB105 3. Area Under the Serum Concentration-Time Curve from Time Zero to Infinity (AUCinf) 4. Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) 5. Maximum Observed Serum Concentration (Cmax) 6. Time to Reach Maximum Observed Serum Concentration (Tmax) 7. Elimination Half-Life (t1/2) in Serum 8. Change From Baseline in Plasma Levels of Neurofilament Light Chain (NfL) Integrated Parts 1 and 2: 1.CSF Through PK Concentration of BIIB105 2.Serum PK Concentration of BIIB105 3.Change From Part 1 Baseline (Cohorts D1, D2) or part 2 baseline (Cohorts A, B, C1, C2) in Plasma Levels of NfL 4.Change From Part 1 Baseline (Cohorts D1, D2) or part 2 baseline (Cohorts A, B, C1, C2) in Slow Vital Capacity (SVC) 5.Change From Part 1 Baseline (Cohorts D1, D2) or part 2 baseline (Cohorts A, B, C1, C2) in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score 6.Change From Part 1 Baseline (Cohorts | — |
Countries
Netherlands
Outcome results
None listed