Amyotrophic Lateral Sclerosis
Conditions
Brief summary
The ALSpire Study is a clinical trial evaluating the investigational drug BIIB105 in adults living with amyotrophic lateral sclerosis (ALS). The ALSpire Study consists of two parts: * Part 1: 6-month placebo-controlled study. During Part 1, participants are randomly assigned to receive either BIIB105 or placebo in a 3:1 or 2:1 ratio (depending on the participant's assigned Cohort). * Part 2: up to 3-year long-term open-label extension. During Part 2, all participants receive BIIB105. The objectives of the study are to evaluate: * The safety and tolerability of BIIB105 in people with ALS * What the body does to BIIB105 (also called pharmacokinetics) * What BIIB105 does to the body (also called pharmacodynamics) * Whether BIIB105 can slow the worsening of clinical function
Detailed description
About BIIB105: \- BIIB105 is an investigational drug designed to reduce the levels of a protein called ATXN2. It is administered intrathecally (via a procedure called lumbar puncture).
Interventions
DRUGBIIB105
Administered as specified in the treatment arm.
DRUGPlacebo
Administered as specified in the treatment arm.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * 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 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 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | From first dose of the study drug in Part 1 up to end of follow up period in Part 1 (up to Day 260) | An AE was 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 SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug. |
| Part 2: Number of Participants With TEAEs and TESAEs | From first dose of the study in Part 2 up to end of follow up period in Part 2 (up to Day 1184) | An AE was 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 SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) | Day 1 | AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf was reported following dose 1 as planned. |
| Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) | Day 1 | AUClast was reported following dose 1 as planned. |
| Part 1: Maximum Observed Serum Concentration (Cmax) | Days 1, 15, 29, 57, 85, 113, 141 and 169 | — |
| Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Days 1, 15, 29, 57, 85, 113, 141 and 169 | — |
| Part 1: Elimination Half-Life (t1/2) in Serum | Day 1 | Elimination half-life (t1/2) was reported following dose 1 as planned. |
| Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Days 29, 57, 85, 113, 130 (For cohorts A, B, C1 and C2)/141 (For cohorts D1 and D2), 169 (For cohorts A, B, C1 and C2)/175 (For cohorts D1 and D2) and 241 | Plasma NfL ratio to baseline was reported in terms of geometric mean ratio. |
| Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Predose on Days 1,15,29,57,85 and on Days 1,15,29,57,85,113,141,169.176,197,210,225,253,281,309,337,365,393,420,448,476,504,532,560,588,616,644,672,700,726,728 | — |
| Part 1: Serum Concentrations of BIIB105 | Pre-dose and 1, 2, 4, 6 hours post-dose on days 1, 15, 29, 57, 85,113, 141, 169 and on days 2, 8, 92, and 176 | — |
| Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 477, 505, 533, 561, 589, 617, 645, 673, 701 | Plasma NfL ratio to baseline was reported in terms of geometric mean ratio. |
| Integrated Part 1 and Part 2: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC) | Baseline, Day 281 | Vital capacity was measured by means of the slow vital capacity (SVC) test using a facemask with the participant sitting upright. SVC was determined by performing at least 3 trials. If the difference between the two highest values of the three trials was ≥10%, then up to 5 trials were performed. The highest percent predicted SVC value at each visit was used for the analysis. Here, baseline is defined as Part 1 day 1 value prior to the study drug. As specified in SAP, change from baseline at Week 40 (Day 281) in least square means and corresponding standard errors was summarized using the analysis of covariance (ANCOVA) model. Negative change from baseline indicates decrease in lung function. |
| Integrated Part 1 and Part 2: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score | Baseline, Day 281 | The ALSFRS-R is a questionnaire that measured degree of impairment in 4 functional domains: respiratory function, bulbar function, gross motor skills, and fine motor skills. Each domain consists of 3 items, each scored from 0 to 4, with higher scores representing better function. Each domain score can have maximum score of 12 calculated as the sum of scores of 3 items for that domain and the total possible score for ALSFRS-R is 48. The total score is the sum of the 4 functional domain scores or all individual item scores if no missing item scores are present. Here, baseline is defined as Part 1 day 1 value prior to the study drug Negative change from baseline indicates disease progression. As specified in SAP change from baseline at Week 40 (Day 281) in least square means and corresponding standard errors was summarized using the ANCOVA model. |
| Integrated Part 1 and Part 2: Change From Baseline in Muscle Strength as Measured by Handheld Dynamometry (HHD) Megascore | Baseline, Day 281 | Quantitative muscle strength was evaluated using HHD, which tested the isometric strength of multiple muscles using standard participant positioning. Approximately 8 muscle groups were examined (per each side) in both upper and lower extremities. The muscle strength values were normalized to Z scores as (post-baseline measurements -mean)/SD and averaged to provide HHD overall megascore. The overall megascore was created by averaging Z scores, if no more than 14 (≤ 14) measures are missing. A Z-score (also called a standard score) is a way to describe how far and in what direction a data point is from the mean of the dataset (in this case, positive values indicate strength and negative values indicate weakness). A Z-score of 0 indicates the population mean, and a positive score indicates muscle strength. A negative change from baseline indicated decreased muscle strength. |
| Integrated Part 1 and Part 2: Time to Death or Permanent Ventilation | Baseline up to Day 1184 | Time to death or permanent ventilation is defined as the time from first dose to death or permanent ventilation ( ≥ 22 hours of mechanical ventilation \[invasive or noninvasive\] per day for ≥ 21 consecutive days), whichever comes first. Participants who did not meet the endpoint definition were censored on the date of participant's last contact in Part 1 or Part 2. Time to death or permanent ventilation data was summarized using Kaplan-Meier curves based on randomization in Part 1. |
| Integrated Parts 1 and 2: Time to Death | Baseline up to Day 1184 | Time to death was defined as the time from first dose to death. |
| Integrated Part 1 and Part 2: Time to Death, Incorporating Post-Study Withdrawal or Study Completion Vital Status Data | Up to Day 1184 | — |
| Integrated Part 1 and Part 2: Serum Concentration of BIIB105 | Up to Day 176 | — |
| Part 1: CSF Concentrations of BIIB105 | Pre-dose on Days 1, 15, 29, 57, 85, 113, 141, 169, and on days 92, 130, 175, and 176 | — |
Countries
Canada, Italy, Netherlands, United States
Participant flow
Recruitment details
Participants diagnosed with amyotrophic lateral sclerosis (ALS) and ALS associated with ataxin-2 (ATXN2) polyCAG expansion (polyQALS) took part in the study at investigational sites in the United States, Netherlands, Canada and Italy from 28 September 2020 to 13 August 2024.
Pre-assignment details
A total of 99 participants were randomized in Part 1 (placebo-controlled) of study to receive BIIB105 or placebo, of which 80 participants completed Part 1. A total of 70 eligible participants who completed Part 1 were enrolled into Part 2 (open-label) of study to receive BIIB105. Part 2 of study was terminated early based on Sponsor's decision.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Pooled Placebo 1+2 Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks. | 28 |
| Part 1: Cohort A: BIIB105 5 mg Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. | 6 |
| Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. | 6 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. | 11 |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks. | 48 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Part 1: Double Blinded Period | Adverse Event | 1 | 0 | 0 | 0 | 3 | 0 | 0 |
| Part 1: Double Blinded Period | Disease Progression - As Defined by the Protocol | 0 | 0 | 0 | 0 | 5 | 0 | 0 |
| Part 1: Double Blinded Period | Protocol Deviation | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1: Double Blinded Period | Reason Not Specified | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1: Double Blinded Period | SubjectWithdrawal-VisitBurden/SchedulingConflict | 0 | 0 | 0 | 1 | 3 | 0 | 0 |
| Part 1: Double Blinded Period | Withdrawal by Subject - Other | 1 | 0 | 1 | 1 | 1 | 0 | 0 |
| Part 2: Open Label Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Part 2: Open Label Period | Death | 0 | 0 | 0 | 0 | 0 | 4 | 2 |
| Part 2: Open Label Period | Disease Progression - As Defined by the Protocol | 0 | 0 | 0 | 0 | 0 | 5 | 6 |
| Part 2: Open Label Period | Lack of Efficacy - Based on Subject Perception | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 2: Open Label Period | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 4 | 35 |
| Part 2: Open Label Period | SubjectWithdrawal-VisitBurden/SchedulingConflict | 0 | 0 | 0 | 0 | 0 | 5 | 4 |
| Part 2: Open Label Period | Withdrawal by Subject - Other | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Part 1: Pooled Placebo 1+2 | Total | Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Cohort B: BIIB105 20 mg | Part 1: Cohort A: BIIB105 5 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 11.15 | 57.5 years STANDARD_DEVIATION 11.83 | 57.7 years STANDARD_DEVIATION 11.45 | 53.3 years STANDARD_DEVIATION 12.77 | 49.3 years STANDARD_DEVIATION 17.84 | 60.5 years STANDARD_DEVIATION 5.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 10 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 88 Participants | 45 Participants | 10 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 00 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not reported due to confidentiality regulations | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 7 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 22 Participants | 83 Participants | 40 Participants | 10 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 9 Participants | 31 Participants | 14 Participants | 3 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 19 Participants | 68 Participants | 34 Participants | 8 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 6 | 0 / 6 | 0 / 11 | 0 / 48 | 4 / 19 | 2 / 51 |
| other Total, other adverse events | 27 / 28 | 6 / 6 | 6 / 6 | 11 / 11 | 47 / 48 | 19 / 19 | 45 / 51 |
| serious Total, serious adverse events | 5 / 28 | 0 / 6 | 0 / 6 | 1 / 11 | 7 / 48 | 7 / 19 | 14 / 51 |
Outcome results
Primary
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An AE was 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 SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug.
Time frame: From first dose of the study drug in Part 1 up to end of follow up period in Part 1 (up to Day 260)
Population: Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 28 Participants |
| Part 1: Pooled Placebo 1+2 | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 5 Participants |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participants |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participants |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 11 Participants |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 48 Participants |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 7 Participants |
Primary
Part 2: Number of Participants With TEAEs and TESAEs
An AE was 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 SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug.
Time frame: From first dose of the study in Part 2 up to end of follow up period in Part 2 (up to Day 1184)
Population: Part 2 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 2: Number of Participants With TEAEs and TESAEs | TEAEs | 19 Participants |
| Part 1: Pooled Placebo 1+2 | Part 2: Number of Participants With TEAEs and TESAEs | TESAEs | 7 Participants |
| Part 1: Cohort A: BIIB105 5 mg | Part 2: Number of Participants With TEAEs and TESAEs | TEAEs | 49 Participants |
| Part 1: Cohort A: BIIB105 5 mg | Part 2: Number of Participants With TEAEs and TESAEs | TESAEs | 14 Participants |
Secondary
Integrated Part 1 and Part 2: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score
The ALSFRS-R is a questionnaire that measured degree of impairment in 4 functional domains: respiratory function, bulbar function, gross motor skills, and fine motor skills. Each domain consists of 3 items, each scored from 0 to 4, with higher scores representing better function. Each domain score can have maximum score of 12 calculated as the sum of scores of 3 items for that domain and the total possible score for ALSFRS-R is 48. The total score is the sum of the 4 functional domain scores or all individual item scores if no missing item scores are present. Here, baseline is defined as Part 1 day 1 value prior to the study drug Negative change from baseline indicates disease progression. As specified in SAP change from baseline at Week 40 (Day 281) in least square means and corresponding standard errors was summarized using the ANCOVA model.
Time frame: Baseline, Day 281
Population: Integrated data for Part 1 and Part 2 was analyzed based on the clinical function population defined for Part 1. The Part 1 clinical function population included participants from the FAS population who have at least 1 postdose measurement in Part 1. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score | -8.46 score on a scale | Standard Error 1.105 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score | -8.26 score on a scale | Standard Error 1.819 |
p-value: =0.920395% CI: [-4.14, 3.74]ANCOVA
Secondary
Integrated Part 1 and Part 2: Change From Baseline in Muscle Strength as Measured by Handheld Dynamometry (HHD) Megascore
Quantitative muscle strength was evaluated using HHD, which tested the isometric strength of multiple muscles using standard participant positioning. Approximately 8 muscle groups were examined (per each side) in both upper and lower extremities. The muscle strength values were normalized to Z scores as (post-baseline measurements -mean)/SD and averaged to provide HHD overall megascore. The overall megascore was created by averaging Z scores, if no more than 14 (≤ 14) measures are missing. A Z-score (also called a standard score) is a way to describe how far and in what direction a data point is from the mean of the dataset (in this case, positive values indicate strength and negative values indicate weakness). A Z-score of 0 indicates the population mean, and a positive score indicates muscle strength. A negative change from baseline indicated decreased muscle strength.
Time frame: Baseline, Day 281
Population: Integrated data for Part 1 and Part 2 was analyzed based on the clinical function population defined for Part 1. The Part 1 clinical function population included participants from the FAS population who have at least 1 postdose measurement in Part 1. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Change From Baseline in Muscle Strength as Measured by Handheld Dynamometry (HHD) Megascore | -0.407 z-score | Standard Deviation 0.3918 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Change From Baseline in Muscle Strength as Measured by Handheld Dynamometry (HHD) Megascore | -0.439 z-score | Standard Deviation 0.4406 |
p-value: =0.106995% CI: [-0.41, 0.04]ANCOVA
Secondary
Integrated Part 1 and Part 2: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC)
Vital capacity was measured by means of the slow vital capacity (SVC) test using a facemask with the participant sitting upright. SVC was determined by performing at least 3 trials. If the difference between the two highest values of the three trials was ≥10%, then up to 5 trials were performed. The highest percent predicted SVC value at each visit was used for the analysis. Here, baseline is defined as Part 1 day 1 value prior to the study drug. As specified in SAP, change from baseline at Week 40 (Day 281) in least square means and corresponding standard errors was summarized using the analysis of covariance (ANCOVA) model. Negative change from baseline indicates decrease in lung function.
Time frame: Baseline, Day 281
Population: Integrated data for Part 1 and Part 2 was analyzed based on the clinical function population defined for Part 1. The Part 1 clinical function population included participants from the FAS population who have at least 1 postdose measurement in Part 1. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC) | -14.49 percent predicted | Standard Error 4.093 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC) | -14.41 percent predicted | Standard Error 7.133 |
p-value: =0.992495% CI: [-15.47, 15.32]ANCOVA
Secondary
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105
Time frame: Predose on Days 1,15,29,57,85 and on Days 1,15,29,57,85,113,141,169.176,197,210,225,253,281,309,337,365,393,420,448,476,504,532,560,588,616,644,672,700,726,728
Population: Integrated Part 1 \& 2=Part 1 PK population.Overall number of participants analyzed=number of participants evaluable for OM analysis.Number analyzed=number of participants evaluable at specified timepoint.Assessment was planned upto Day 1093 however,no assessments were conducted after Day 729 due to early termination.Treatment groups for integrated analysis of Parts 1 \& 2 were planned for Early-start BIIB105 120 mg \& Placebo/Delayed-start BIIB105,\& results are reported for these treatment groups.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 728 | 26.28 ng/mL | — |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 281 | 26.51 ng/mL | Geometric Coefficient of Variation 73.96 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 309 | 27.14 ng/mL | Geometric Coefficient of Variation 63.54 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 337 | 31.34 ng/mL | Geometric Coefficient of Variation 71.84 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 365 | 30.16 ng/mL | Geometric Coefficient of Variation 62.35 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 393 | 23.56 ng/mL | Geometric Coefficient of Variation 31.29 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 420 | 25.84 ng/mL | Geometric Coefficient of Variation 42.82 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 448 | 23.53 ng/mL | Geometric Coefficient of Variation 40.75 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 476 | 30.87 ng/mL | Geometric Coefficient of Variation 28.29 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 504 | 28.24 ng/mL | Geometric Coefficient of Variation 38.06 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 532 | 26.73 ng/mL | Geometric Coefficient of Variation 44.19 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 560 | 26.42 ng/mL | Geometric Coefficient of Variation 36.82 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 588 | 40.26 ng/mL | Geometric Coefficient of Variation 68 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 616 | 24.69 ng/mL | Geometric Coefficient of Variation 109.22 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 644 | 21.15 ng/mL | Geometric Coefficient of Variation 39.95 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 672 | 30.75 ng/mL | Geometric Coefficient of Variation 48.18 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 700 | 23.85 ng/mL | Geometric Coefficient of Variation 1.63 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 726 | 28.22 ng/mL | — |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 1 : Pre-dose | 0.13 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 15 : Pre-dose | 14.54 ng/mL | Geometric Coefficient of Variation 82.48 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 15 | 31.04 ng/mL | — |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 29: Pre-dose | 17.53 ng/mL | Geometric Coefficient of Variation 95.18 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 57 : Pre-dose | 10.29 ng/mL | Geometric Coefficient of Variation 79.9 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 85 : Pre-dose | 14.06 ng/mL | Geometric Coefficient of Variation 77.42 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 113 | 17.08 ng/mL | Geometric Coefficient of Variation 86.41 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 141 | 17.91 ng/mL | Geometric Coefficient of Variation 84.83 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 169 | 18.88 ng/mL | Geometric Coefficient of Variation 74.23 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 176 | 17.35 ng/mL | Geometric Coefficient of Variation 0.04 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 197 | 24.88 ng/mL | Geometric Coefficient of Variation 57.69 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 210 | 49.04 ng/mL | Geometric Coefficient of Variation 67.88 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 225 | 24.14 ng/mL | Geometric Coefficient of Variation 63.21 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 253 | 23.54 ng/mL | Geometric Coefficient of Variation 62.86 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 1 | 0.15 ng/mL | Geometric Coefficient of Variation 37.88 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 197 | 24.99 ng/mL | Geometric Coefficient of Variation 71.18 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 448 | 28.43 ng/mL | — |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 15 | 12.93 ng/mL | Geometric Coefficient of Variation 70.31 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 337 | 22.11 ng/mL | Geometric Coefficient of Variation 16.8 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 29 | 18.62 ng/mL | Geometric Coefficient of Variation 93.41 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 225 | 30.52 ng/mL | Geometric Coefficient of Variation 13.97 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 57 | 9.72 ng/mL | Geometric Coefficient of Variation 49.08 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 420 | 21.91 ng/mL | — |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 85 | 14.54 ng/mL | Geometric Coefficient of Variation 63.76 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 253 | 21.68 ng/mL | Geometric Coefficient of Variation 70.34 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 113 | 20.70 ng/mL | Geometric Coefficient of Variation 56.82 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 476 | 25.95 ng/mL | — |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 141 | 24.50 ng/mL | Geometric Coefficient of Variation 30.13 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 281 | 23.79 ng/mL | Geometric Coefficient of Variation 8.69 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 169 | 19.32 ng/mL | Geometric Coefficient of Variation 36.08 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 393 | 15.36 ng/mL | Geometric Coefficient of Variation 13.95 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 | Day 309 | 30.47 ng/mL | Geometric Coefficient of Variation 13.01 |
Secondary
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
Plasma NfL ratio to baseline was reported in terms of geometric mean ratio.
Time frame: Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 477, 505, 533, 561, 589, 617, 645, 673, 701
Population: Integrated Parts 1 and 2=Part 1 PD population. Number analyzed indicates the number of participants evaluable for the OM at the specified timepoint. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 673 | 0.66 ratio | Geometric Coefficient of Variation 30.22 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 29 | 1.15 ratio | Geometric Coefficient of Variation 72.72 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 113 | 1.01 ratio | Geometric Coefficient of Variation 21.77 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 141 | 1.03 ratio | Geometric Coefficient of Variation 41.35 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 169 | 1.06 ratio | Geometric Coefficient of Variation 24.92 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 197 | 1.08 ratio | Geometric Coefficient of Variation 28.28 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 225 | 1.12 ratio | Geometric Coefficient of Variation 38.42 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 253 | 1.15 ratio | Geometric Coefficient of Variation 28.4 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 281 | 1.14 ratio | Geometric Coefficient of Variation 26.57 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 309 | 1.07 ratio | Geometric Coefficient of Variation 31.81 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 337 | 1.05 ratio | Geometric Coefficient of Variation 38.67 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 365 | 0.99 ratio | Geometric Coefficient of Variation 32.42 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 393 | 0.95 ratio | Geometric Coefficient of Variation 48.05 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 421 | 0.92 ratio | Geometric Coefficient of Variation 36.61 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 449 | 0.82 ratio | Geometric Coefficient of Variation 28.9 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 477 | 0.85 ratio | Geometric Coefficient of Variation 23.15 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 505 | 0.77 ratio | Geometric Coefficient of Variation 25.18 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 533 | 0.78 ratio | Geometric Coefficient of Variation 14.58 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 561 | 0.65 ratio | Geometric Coefficient of Variation 14.63 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 589 | 0.77 ratio | Geometric Coefficient of Variation 39.28 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 617 | 0.80 ratio | Geometric Coefficient of Variation 38.48 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 645 | 0.76 ratio | Geometric Coefficient of Variation 52.68 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 701 | 0.54 ratio | — |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 57 | 1.03 ratio | Geometric Coefficient of Variation 21.7 |
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 85 | 0.99 ratio | Geometric Coefficient of Variation 19.62 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 29 | 1.03 ratio | Geometric Coefficient of Variation 22.35 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 533 | 1.15 ratio | Geometric Coefficient of Variation 32.24 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 57 | 1.11 ratio | Geometric Coefficient of Variation 18.9 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 337 | 1.18 ratio | Geometric Coefficient of Variation 23.3 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 85 | 1.00 ratio | Geometric Coefficient of Variation 18 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 477 | 0.92 ratio | Geometric Coefficient of Variation 32.52 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 113 | 1.06 ratio | Geometric Coefficient of Variation 19.95 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 365 | 1.20 ratio | Geometric Coefficient of Variation 29.59 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 141 | 1.10 ratio | Geometric Coefficient of Variation 20.84 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 589 | 0.90 ratio | Geometric Coefficient of Variation 23.38 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 169 | 1.06 ratio | Geometric Coefficient of Variation 20.33 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 393 | 1.26 ratio | Geometric Coefficient of Variation 24.88 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 197 | 1.08 ratio | Geometric Coefficient of Variation 23.6 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 505 | 0.88 ratio | Geometric Coefficient of Variation 46.94 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 225 | 1.12 ratio | Geometric Coefficient of Variation 31.12 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 421 | 1.21 ratio | Geometric Coefficient of Variation 58.82 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 253 | 1.06 ratio | Geometric Coefficient of Variation 27.71 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 617 | 0.70 ratio | — |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 281 | 1.18 ratio | Geometric Coefficient of Variation 21.26 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 449 | 1.06 ratio | Geometric Coefficient of Variation 32.94 |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 309 | 1.09 ratio | Geometric Coefficient of Variation 24.46 |
Secondary
Integrated Part 1 and Part 2: Serum Concentration of BIIB105
Time frame: Up to Day 176
Population: Assessments were planned upto Day 1009 for this OM;however no assessments were conducted after Day 176 due to early termination.Serum concentrations of BIIB105 were not estimable for Integrated Parts 1 \& 2.Data collected for serum PK concentrations for Parts 1 \& 2 are reported in OM #3 and #20(post-hoc)respectively.Treatment groups for integrated analysis of Parts 1 \& 2 were planned for Early-start BIIB105 120 mg \& Placebo/Delayed-start BIIB105,\& results are reported for these treatment groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Serum Concentration of BIIB105 | NA ng/mL |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Serum Concentration of BIIB105 | NA ng/mL |
Secondary
Integrated Part 1 and Part 2: Time to Death, Incorporating Post-Study Withdrawal or Study Completion Vital Status Data
Time frame: Up to Day 1184
Population: As per the changes to the protocol-specified analyses mentioned in the SAP, time to death, incorporating post-study withdrawal or study completion vital status data was not performed as post-study withdrawal vital status data was not collected at the time of this analysis. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.
Secondary
Integrated Part 1 and Part 2: Time to Death or Permanent Ventilation
Time to death or permanent ventilation is defined as the time from first dose to death or permanent ventilation ( ≥ 22 hours of mechanical ventilation \[invasive or noninvasive\] per day for ≥ 21 consecutive days), whichever comes first. Participants who did not meet the endpoint definition were censored on the date of participant's last contact in Part 1 or Part 2. Time to death or permanent ventilation data was summarized using Kaplan-Meier curves based on randomization in Part 1.
Time frame: Baseline up to Day 1184
Population: Integrated data for Part 1 and Part 2 was analyzed based on the FAS population defined for Part 1. Part 1 FAS population included all randomized participants who received at least 1 dose of study treatment in Part 1 and 2. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pooled Placebo 1+2 | Integrated Part 1 and Part 2: Time to Death or Permanent Ventilation | NA weeks |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Part 1 and Part 2: Time to Death or Permanent Ventilation | NA weeks |
p-value: =0.100395% CI: [0.433, 42.587]Log Rank
Secondary
Integrated Parts 1 and 2: Time to Death
Time to death was defined as the time from first dose to death.
Time frame: Baseline up to Day 1184
Population: Integrated data for Part 1 and Part 2 was analyzed based on the FAS population defined for Part 1. Part 1 FAS population included all randomized participants who received at least 1 dose of study treatment in Part 1 and 2. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pooled Placebo 1+2 | Integrated Parts 1 and 2: Time to Death | NA weeks |
| Part 1: Cohort A: BIIB105 5 mg | Integrated Parts 1 and 2: Time to Death | NA weeks |
p-value: =0.1143Kaplan-Meier product limit method
Secondary
Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf)
AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf was reported following dose 1 as planned.
Time frame: Day 1
Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Overall number of participants analyzed' signifies number of participants with data available for OM analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) | 934.22 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 52.89 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) | 3546.89 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 53.5 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) | 11258.45 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 14.57 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) | 24466.44 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 30.24 |
Secondary
Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast)
AUClast was reported following dose 1 as planned.
Time frame: Day 1
Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Overall number of participants analyzed' signifies number of participants with data available for OM analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) | 574.59 h*ng/mL | Geometric Coefficient of Variation 79.16 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) | 3239.40 h*ng/mL | Geometric Coefficient of Variation 52.73 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) | 11758.68 h*ng/mL | Geometric Coefficient of Variation 21.12 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) | 24289.70 h*ng/mL | Geometric Coefficient of Variation 30.5 |
Secondary
Part 1: CSF Concentrations of BIIB105
Time frame: Pre-dose on Days 1, 15, 29, 57, 85, 113, 141, 169, and on days 92, 130, 175, and 176
Population: The Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Number analyzed (n)' signifies number of participants evaluable for this OM at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: CSF Concentrations of BIIB105 | Day 15 : Pre-dose | 1.93 ng/mL | Geometric Coefficient of Variation 41.54 |
| Part 1: Pooled Placebo 1+2 | Part 1: CSF Concentrations of BIIB105 | Day 92 | 5.01 ng/mL | Geometric Coefficient of Variation 30.62 |
| Part 1: Pooled Placebo 1+2 | Part 1: CSF Concentrations of BIIB105 | Day 29 : Pre-dose | 3.53 ng/mL | Geometric Coefficient of Variation 33.52 |
| Part 1: Pooled Placebo 1+2 | Part 1: CSF Concentrations of BIIB105 | Day 85 : Pre-dose | 2.37 ng/mL | Geometric Coefficient of Variation 30.35 |
| Part 1: Pooled Placebo 1+2 | Part 1: CSF Concentrations of BIIB105 | Day 175 | 1.16 ng/mL | Geometric Coefficient of Variation 54.77 |
| Part 1: Pooled Placebo 1+2 | Part 1: CSF Concentrations of BIIB105 | Day 57 : Pre-dose | 2.32 ng/mL | Geometric Coefficient of Variation 28.96 |
| Part 1: Pooled Placebo 1+2 | Part 1: CSF Concentrations of BIIB105 | Day 130 | 2.09 ng/mL | Geometric Coefficient of Variation 32.22 |
| Part 1: Pooled Placebo 1+2 | Part 1: CSF Concentrations of BIIB105 | Day 1 : Pre-dose | 0.00 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: CSF Concentrations of BIIB105 | Day 175 | 1.16 ng/mL | Geometric Coefficient of Variation 36.06 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: CSF Concentrations of BIIB105 | Day 85 : Pre-dose | 3.18 ng/mL | Geometric Coefficient of Variation 72.73 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: CSF Concentrations of BIIB105 | Day 92 | 6.28 ng/mL | Geometric Coefficient of Variation 74.45 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: CSF Concentrations of BIIB105 | Day 15 : Pre-dose | 2.71 ng/mL | Geometric Coefficient of Variation 55.21 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: CSF Concentrations of BIIB105 | Day 130 | 2.45 ng/mL | Geometric Coefficient of Variation 57.06 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: CSF Concentrations of BIIB105 | Day 1 : Pre-dose | 0.00 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: CSF Concentrations of BIIB105 | Day 29 : Pre-dose | 4.32 ng/mL | Geometric Coefficient of Variation 52.42 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: CSF Concentrations of BIIB105 | Day 57 : Pre-dose | 2.65 ng/mL | Geometric Coefficient of Variation 46.23 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: CSF Concentrations of BIIB105 | Day 92 | 25.51 ng/mL | Geometric Coefficient of Variation 66.26 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: CSF Concentrations of BIIB105 | Day 130 | 5.42 ng/mL | Geometric Coefficient of Variation 40.72 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: CSF Concentrations of BIIB105 | Day 15 : Pre-dose | 5.75 ng/mL | Geometric Coefficient of Variation 62.33 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: CSF Concentrations of BIIB105 | Day 175 | 2.68 ng/mL | Geometric Coefficient of Variation 46.05 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: CSF Concentrations of BIIB105 | Day 1 : Pre-dose | 0.00 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: CSF Concentrations of BIIB105 | Day 29 : Pre-dose | 11.53 ng/mL | Geometric Coefficient of Variation 49.38 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: CSF Concentrations of BIIB105 | Day 57 : Pre-dose | 4.82 ng/mL | Geometric Coefficient of Variation 59.33 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: CSF Concentrations of BIIB105 | Day 85 : Pre-dose | 6.50 ng/mL | Geometric Coefficient of Variation 36.23 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 176 | 17.35 ng/mL | Geometric Coefficient of Variation 0.04 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 1 : Pre-dose | 0.00 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 29 : Pre-dose | 17.53 ng/mL | Geometric Coefficient of Variation 95.18 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 15 : Pre-dose | 14.54 ng/mL | Geometric Coefficient of Variation 82.48 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 57 : Pre-dose | 10.29 ng/mL | Geometric Coefficient of Variation 79.9 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 85 : Pre-dose | 14.06 ng/mL | Geometric Coefficient of Variation 77.42 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 113 | 17.08 ng/mL | Geometric Coefficient of Variation 86.41 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 141 | 17.91 ng/mL | Geometric Coefficient of Variation 84.83 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: CSF Concentrations of BIIB105 | Day 169 | 18.88 ng/mL | Geometric Coefficient of Variation 74.23 |
Secondary
Part 1: Elimination Half-Life (t1/2) in Serum
Elimination half-life (t1/2) was reported following dose 1 as planned.
Time frame: Day 1
Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. ''Overall number of participants (n)' signifies number of participants evaluable for this OM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: Elimination Half-Life (t1/2) in Serum | 14.0 hour |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Elimination Half-Life (t1/2) in Serum | 26.6 hour |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Elimination Half-Life (t1/2) in Serum | 41.7 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Elimination Half-Life (t1/2) in Serum | 39.8 hour |
Secondary
Part 1: Maximum Observed Serum Concentration (Cmax)
Time frame: Days 1, 15, 29, 57, 85, 113, 141 and 169
Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Number analyzed (n)' signifies number of participants evaluable for this OM at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 15 | 31.03 ng/mL | Geometric Coefficient of Variation 78.23 |
| Part 1: Pooled Placebo 1+2 | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 85 | 31.43 ng/mL | Geometric Coefficient of Variation 117.43 |
| Part 1: Pooled Placebo 1+2 | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 1 | 52.18 ng/mL | Geometric Coefficient of Variation 123.13 |
| Part 1: Pooled Placebo 1+2 | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 29 | 34.11 ng/mL | Geometric Coefficient of Variation 119.62 |
| Part 1: Pooled Placebo 1+2 | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 57 | 31.92 ng/mL | Geometric Coefficient of Variation 136.57 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 57 | 94.60 ng/mL | Geometric Coefficient of Variation 75.3 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 1 | 227.80 ng/mL | Geometric Coefficient of Variation 73.2 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 85 | 168.38 ng/mL | Geometric Coefficient of Variation 59.96 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 29 | 164.15 ng/mL | Geometric Coefficient of Variation 101.46 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 15 | 165.37 ng/mL | Geometric Coefficient of Variation 118.45 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 29 | 616.02 ng/mL | Geometric Coefficient of Variation 61.54 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 1 | 644.10 ng/mL | Geometric Coefficient of Variation 55.31 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 57 | 513.84 ng/mL | Geometric Coefficient of Variation 98.01 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 15 | 495.03 ng/mL | Geometric Coefficient of Variation 76.73 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 85 | 476.91 ng/mL | Geometric Coefficient of Variation 75.87 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 169 | 957.24 ng/mL | Geometric Coefficient of Variation 86.51 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 1 | 1019.11 ng/mL | Geometric Coefficient of Variation 76.61 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 15 | 1312.42 ng/mL | Geometric Coefficient of Variation 93.96 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 29 | 1173.71 ng/mL | Geometric Coefficient of Variation 75.74 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 57 | 1052.70 ng/mL | Geometric Coefficient of Variation 99.57 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 85 | 1009.44 ng/mL | Geometric Coefficient of Variation 84.68 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 113 | 949.58 ng/mL | Geometric Coefficient of Variation 83.69 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Maximum Observed Serum Concentration (Cmax) | Day 141 | 1243.75 ng/mL | Geometric Coefficient of Variation 91.13 |
Secondary
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
Plasma NfL ratio to baseline was reported in terms of geometric mean ratio.
Time frame: Days 29, 57, 85, 113, 130 (For cohorts A, B, C1 and C2)/141 (For cohorts D1 and D2), 169 (For cohorts A, B, C1 and C2)/175 (For cohorts D1 and D2) and 241
Population: The Part 1 pharmacodynamic (PD) population included participants who received at least 1 dose of study treatment and have at least 1 available postdose evaluation of the respective PD endpoint in the study in Part 1. 'Number analyzed (n)' indicates the number of participants evaluable for the OM at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 57 | 1.08 ratio | Geometric Coefficient of Variation 19.91 |
| Part 1: Pooled Placebo 1+2 | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 169 (A,B,C1,C2)/Day 175 (D1,D2) | 1.10 ratio | Geometric Coefficient of Variation 23.67 |
| Part 1: Pooled Placebo 1+2 | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 85 | 0.99 ratio | Geometric Coefficient of Variation 17.27 |
| Part 1: Pooled Placebo 1+2 | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 113 | 1.06 ratio | Geometric Coefficient of Variation 19.95 |
| Part 1: Pooled Placebo 1+2 | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 29 | 1.04 ratio | Geometric Coefficient of Variation 20.32 |
| Part 1: Pooled Placebo 1+2 | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 130 (A,B,C1,C2)/Day 141 (D1,D2) | 1.09 ratio | Geometric Coefficient of Variation 20.46 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 130 (A,B,C1,C2)/Day 141 (D1,D2) | 1.10 ratio | Geometric Coefficient of Variation 8.58 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 169 (A,B,C1,C2)/Day 175 (D1,D2) | 1.02 ratio | Geometric Coefficient of Variation 22.58 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 57 | 0.95 ratio | Geometric Coefficient of Variation 14.63 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 85 | 0.99 ratio | Geometric Coefficient of Variation 15.7 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 29 | 1.05 ratio | Geometric Coefficient of Variation 8.47 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 29 | 0.83 ratio | Geometric Coefficient of Variation 47.1 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 85 | 0.98 ratio | Geometric Coefficient of Variation 26.4 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 169 (A,B,C1,C2)/Day 175 (D1,D2) | 1.10 ratio | Geometric Coefficient of Variation 24.55 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 57 | 0.97 ratio | Geometric Coefficient of Variation 15.95 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 130 (A,B,C1,C2)/Day 141 (D1,D2) | 0.92 ratio | Geometric Coefficient of Variation 40.79 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 85 | 1.11 ratio | Geometric Coefficient of Variation 19.85 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 57 | 1.08 ratio | Geometric Coefficient of Variation 20.43 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 130 (A,B,C1,C2)/Day 141 (D1,D2) | 0.99 ratio | Geometric Coefficient of Variation 30.8 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 29 | 1.06 ratio | Geometric Coefficient of Variation 11.23 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 169 (A,B,C1,C2)/Day 175 (D1,D2) | 1.08 ratio | Geometric Coefficient of Variation 29.73 |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 214 | 1.07 ratio | — |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 29 | 1.15 ratio | Geometric Coefficient of Variation 72.72 |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 57 | 1.03 ratio | Geometric Coefficient of Variation 21.7 |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 85 | 0.99 ratio | Geometric Coefficient of Variation 19.62 |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 113 | 1.01 ratio | Geometric Coefficient of Variation 21.77 |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 130 (A,B,C1,C2)/Day 141 (D1,D2) | 1.03 ratio | Geometric Coefficient of Variation 41.35 |
| Part 1: Cohorts D1 + D2: BIIB105 120 mg | Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline | Day 169 (A,B,C1,C2)/Day 175 (D1,D2) | 1.06 ratio | Geometric Coefficient of Variation 24.92 |
Secondary
Part 1: Serum Concentrations of BIIB105
Time frame: Pre-dose and 1, 2, 4, 6 hours post-dose on days 1, 15, 29, 57, 85,113, 141, 169 and on days 2, 8, 92, and 176
Population: The Part 1 pharmacokinetic (PK) analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or cerebrospinal fluid (CSF) BIIB105 measurement in Part 1. 'Number analyzed (n)' signifies number of participants evaluable for this outcome measure (OM) at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 15: 1 HR post-dose | 3.85 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 172.7 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 1: 1 HR post-dose | 7.21 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 500.18 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 1: 2 HR post-dose | 32.20 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 177.01 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 1: 4 HR post-dose | 41.38 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 125.95 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 1: 6 HR post-dose | 39.27 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 102.97 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 2 | 6.76 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 65.9 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 8 | 0.46 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18.74 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 15: Pre-dose | 0.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 1: Pre-dose | 0.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 15: 2 HR post-dose | 16.89 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 111.49 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 15: 4 HR post-dose | 30.07 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.48 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 15: 6 HR post-dose | 27.28 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 106.96 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 29: Pre-dose | 0.45 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24.48 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 29: 1 HR post-dose | 5.80 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 117.9 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 29: 2 HR post-dose | 16.53 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 121.68 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 29: 4 HR post-dose | 31.29 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 120.91 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 29: 6 HR post-dose | 33.28 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 127.43 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 57: Pre-dose | 0.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 57: 1 HR post-dose | 7.45 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 275.61 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 57: 2 HR post-dose | 22.05 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 153.51 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 57: 4 HR post-dose | 27.72 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 123.67 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 57: 6 HR post-dose | 27.33 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 105.3 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 85: Pre-dose | 0.50 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 85: 1 HR post-dose | 7.02 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 111.81 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 85: 2 HR post-dose | 20.60 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 95.33 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 85: 4 HR post-dose | 27.69 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 111.28 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 85: 6 HR post-dose | 29.83 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 119.17 |
| Part 1: Pooled Placebo 1+2 | Part 1: Serum Concentrations of BIIB105 | Day 92 | 0.43 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23.54 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 8 | 0.47 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.02 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 6 HR post-dose | 89.38 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.82 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: Pre-dose | 0.40 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.26 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 2 HR post-dose | 51.58 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 602.03 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 1 HR post-dose | 18.91 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 240.4 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 4 HR post-dose | 139.75 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 137.49 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 2 HR post-dose | 69.04 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 265.82 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 4 HR post-dose | 102.80 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 200.28 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: Pre-dose | 0.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 1 HR post-dose | 22.24 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 226.26 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 4 HR post-dose | 140.04 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 91 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 1 HR post-dose | 57.70 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 285.3 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 2 HR post-dose | 135.71 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 109.27 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 6 HR post-dose | 151.47 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 87.99 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 4 HR post-dose | 211.34 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 68.29 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 6 HR post-dose | 139.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 98.33 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 6 HR post-dose | 165.05 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 60.63 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: Pre-dose | 0.41 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 21.53 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 6 HR post-dose | 140.74 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.95 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 2 | 29.07 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 76.82 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: Pre-dose | 0.50 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20.12 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 92 | 0.56 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47.98 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 1 HR post-dose | 7.98 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 159.54 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: Pre-dose | 0.48 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.47 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 2 HR post-dose | 26.59 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 107.62 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 2 HR post-dose | 94.51 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 140.45 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 4 HR post-dose | 74.60 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 85.53 |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 1 HR post-dose | 16.45 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 557.48 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 6 HR post-dose | 555.65 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.83 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 8 | 1.38 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.15 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 6 HR post-dose | 416.91 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 94.12 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: Pre-dose | 0.78 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.94 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 92 | 2.05 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 92.02 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 4 HR post-dose | 488.11 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51.22 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: Pre-dose | 0.74 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.453 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: Pre-dose | 1.23 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.84 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 2 HR post-dose | 420.39 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 116.92 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 6 HR post-dose | 411.61 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.33 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 1 HR post-dose | 77.63 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 142.75 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 2 HR post-dose | 246.73 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 142.61 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 4 HR post-dose | 363.86 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 77.37 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 6 HR post-dose | 528.45 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 61.49 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 2 HR post-dose | 248.33 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 84.14 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 2 HR post-dose | 274.02 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 128.39 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 4 HR post-dose | 566.43 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71.83 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 1 HR post-dose | 44.33 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 615.14 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: Pre-dose | 0.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 4 HR post-dose | 471.12 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 95.76 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 2 | 118.70 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 103.89 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: Pre-dose | 0.79 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 80.26 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 1 HR post-dose | 34.98 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 465.78 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 1 HR post-dose | 56.01 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 489.04 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 4 HR post-dose | 416.74 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 80.9 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 6 HR post-dose | 453.58 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.39 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 2 HR post-dose | 250.28 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 101.57 |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 1 HR post-dose | 114.69 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 226.87 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 8 | 2.97 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43.6 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: Pre-dose | 1.90 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43.15 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 176 | 6.97 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 132.41 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 1 HR post-dose | 257.73 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 290.21 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 2 HR post-dose | 972.44 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 110.25 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 4 HR post-dose | 996.20 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 83.48 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 92 | 4.47 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.1 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 15: 6 HR post-dose | 897.25 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78.56 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 113: Pre-dose | 1.95 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 59.79 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: Pre-dose | 2.59 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 59.99 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 113: 1 HR post-dose | 193.04 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 198.68 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 1 HR post-dose | 248.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 152.63 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 113: 2 HR post-dose | 632.28 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 91.07 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 2 HR post-dose | 773.11 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 95.92 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 113: 4 HR post-dose | 802.46 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 91.76 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 4 HR post-dose | 953.50 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 80.75 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 113: 6 HR post-dose | 858.58 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 86.76 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 29: 6 HR post-dose | 942.06 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 141: Pre-dose | 2.07 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 80.82 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: Pre-dose | 1.83 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69.8 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 141: 1 HR post-dose | 457.25 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 162.57 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 1 HR post-dose | 227.06 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 214.59 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 141: 2 HR post-dose | 949.31 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 120.4 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 2 HR post-dose | 713.36 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 122.48 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 141: 4 HR post-dose | 1044.80 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 101.09 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 4 HR post-dose | 887.82 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 105.32 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 141: 6 HR post-dose | 996.44 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 85.54 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 57: 6 HR post-dose | 889.54 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 89.2 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 169: Pre-dose | 2.95 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 153.02 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: Pre-dose | 1.91 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 113.18 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 169: 1 HR post-dose | 288.75 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 217.19 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 1 HR post-dose | 231.31 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 236.91 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 169: 2 HR post-dose | 702.24 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 107.1 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 2 HR post-dose | 651.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 127.92 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 169: 4 HR post-dose | 816.90 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 86.61 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: Pre-dose | 0.00 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 1 HR post-dose | 187.14 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 351.05 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 2 HR post-dose | 620.38 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 132.37 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 4 HR post-dose | 799.70 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 89.26 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 4 HR post-dose | 798.21 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 86.03 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 169: 6 HR post-dose | 683.89 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 158.85 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 1: 6 HR post-dose | 774.73 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 60.51 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 2 | 260.03 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 67.59 |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Serum Concentrations of BIIB105 | Day 85: 6 HR post-dose | 837.50 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 73.65 |
Secondary
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax)
Time frame: Days 1, 15, 29, 57, 85, 113, 141 and 169
Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Number analyzed (n)' signifies number of participants evaluable for this OM at the specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 29 | 5.8 hour |
| Part 1: Pooled Placebo 1+2 | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 15 | 5.0 hour |
| Part 1: Pooled Placebo 1+2 | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 1 | 4.2 hour |
| Part 1: Pooled Placebo 1+2 | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 57 | 5.8 hour |
| Part 1: Pooled Placebo 1+2 | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 85 | 5.1 hour |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 57 | 5.0 hour |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 1 | 4.2 hour |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 15 | 5.0 hour |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 29 | 5.8 hour |
| Part 1: Cohort A: BIIB105 5 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 85 | 4.3 hour |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 85 | 5.8 hour |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 29 | 4.2 hour |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 1 | 5.8 hour |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 15 | 5.9 hour |
| Part 1: Cohort B: BIIB105 20 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 57 | 4.2 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 85 | 5.8 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 113 | 5.3 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 1 | 4.3 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 15 | 4.1 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 141 | 4.0 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 29 | 4.1 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 57 | 4.5 hour |
| Part 1: Cohorts C1+C2: BIIB105 60 mg | Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Day 169 | 4.1 hour |
Post Hoc
Part 2: Serum Concentration of BIIB105
Time frame: Days 1, 169, 337, 505 and 673
Population: The PK analysis population is defined as all randomized participants who received at least 1 dose of study treatment and have at least 1 postdose serum and/or CSF BIIB105 measurement. 'Number analyzed' indicates the number of participants evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pooled Placebo 1+2 | Part 2: Serum Concentration of BIIB105 | Day 673 | 18.89 ng/mL | Geometric Coefficient of Variation 164.41 |
| Part 1: Pooled Placebo 1+2 | Part 2: Serum Concentration of BIIB105 | Day 169 | 1.25 ng/mL | Geometric Coefficient of Variation 186.75 |
| Part 1: Pooled Placebo 1+2 | Part 2: Serum Concentration of BIIB105 | Day 337 | 2.46 ng/mL | Geometric Coefficient of Variation 333.2 |
| Part 1: Pooled Placebo 1+2 | Part 2: Serum Concentration of BIIB105 | Day 505 | 3.53 ng/mL | Geometric Coefficient of Variation 340.11 |
| Part 1: Pooled Placebo 1+2 | Part 2: Serum Concentration of BIIB105 | Day 1 | 0.50 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Cohort A: BIIB105 5 mg | Part 2: Serum Concentration of BIIB105 | Day 1 | 1.47 ng/mL | Geometric Coefficient of Variation 139 |
| Part 1: Cohort A: BIIB105 5 mg | Part 2: Serum Concentration of BIIB105 | Day 337 | 2.50 ng/mL | Geometric Coefficient of Variation 95.95 |
| Part 1: Cohort A: BIIB105 5 mg | Part 2: Serum Concentration of BIIB105 | Day 169 | 3.50 ng/mL | Geometric Coefficient of Variation 151.48 |
| Part 1: Cohort A: BIIB105 5 mg | Part 2: Serum Concentration of BIIB105 | Day 505 | 8.54 ng/mL | Geometric Coefficient of Variation 0 |