Eligibility
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.
- No known presence or family history of mutations in the superoxide 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 Federation 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
cytosine-adenine-guanine/cytosine-adenine-adenine (CAG/CAA) repeat expansion in the
ataxin-2 (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 Cohort 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 (Day 1). 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 informed consent and
authorization to use protected health information in accordance with national and
local privacy regulations
- Participants must have completed Study NCT04494256 Part 1 through Week 25 (Day 175
Visit for Cohorts A, B, C1, C2; Day 176 Visit for Cohorts D1, D2). This inclusion
criterion does not apply to a participant if Part 1 was terminated by the Sponsor
before the participant reached Week 25.
- Participants from Cohorts A, B, C1, and C2 must have a washout of ≥16 weeks between
the last dose of study treatment received in Study NCT04494256 Part 1 and the first
dose of BIIB105 received in Study NCT04494256 Part 2. Participants from Cohorts D1 and
D2 do not require a washout period.
- 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 (Day 1). 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, INR, PT, and aPTT
should be within normal ranges.
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 ≤6 months of Screening that would limit
participation in the study, as determined by the Investigator.
- Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing
system during the study period.
- Presence of tracheostomy.
- In participants from Cohorts A, B, C1, and D1, history of myocardial infarction, as
determined by the Investigator.
- In participants from Cohorts A, B, C1, and D1, poorly controlled type 1 or 2 diabetes
mellitus defined as hemoglobin A1c (HbA1c) ≥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
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 asymptomatic, 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 ≤ 6 months of Screening that would limit
participation in the study, as determined by the Investigator.
- Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing
system during the study period.
- In participants from Cohorts A, B, C1, and D1, history of myocardial infarction, as
determined by the Investigator.
- In participants from Cohorts A, B, C1, and D1, poorly controlled type 1 or 2 diabetes
mellitus defined as HbA1c ≥8% during Screening.
- Treatment with another investigational drug (including investigational drugs for ALS
through compassionate use programs; excluding BIIB105) or biological agent within 1
month or 5 half-lives of study agent, whichever is longer, before Screening.
- Treatment with an antiplatelet or anticoagulant therapy that cannot safely be
interrupted for 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.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.