Multiple Sclerosis
Conditions
Brief summary
The primary objective of the study is to evaluate the efficacy of BIIB033 in participants with active relapsing multiple sclerosis (MS) when used concurrently with Avonex. Secondary objectives of this study in this study population are to assess the safety, tolerability, and population pharmacokinetics of BIIB033 when used concurrently with Avonex.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 58 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of relapsing remitting MS (RRMS) or onset of secondary progressive MS (SPMS) * RRMS and SPMS subjects must have evidence of ongoing disease activity within 12 months of enrollment. * All male and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after their last dose of study treatment Key
Exclusion criteria
* A MS relapse that has occurred within the 90 days prior to Day 1/Baseline and/or the subject has not stabilized from a previous relapse prior to Screening * Previous history of clinically significant disease. * Plans to undergo elective major procedures/surgeries at any time during the study. * Treatment with any investigational MS drugs within 3 weeks or 5 times the half life (whichever is longer) prior to Day 1/Baseline * RRMS subjects with any history of inadequate response to any approved interferon β preparation * History of human immunodeficiency virus (HIV), hepatitis C virus antibody, or hepatitis B virus * History or evidence of drug or alcohol abuse within 2 years prior to randomization Note: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint | 72 weeks | Estimated proportion of participants experiencing confirmed improvement in any 1 or more of the following components: a ≥1 point decrease in the Expanded Disability Status Scale (EDSS) score from a baseline score of \<=6.0 (decrease sustained for ≥3 months); a ≥15% improvement from baseline in time to complete 9-Hole Peg Test (9HPT) by either hand (improvement sustained for ≥3 months for the same hand), where the time is the average time of 2 trials per hand at the same visit; a ≥15% improvement from baseline in time to complete Timed 25-Foot Walk (T25FW) test (improvement sustained for ≥3 months), where the time is the average time of 2 trials at the same visit; or a ≥15% improvement from baseline 3-Second Paced Auditory Serial Addition Test (PASAT-3) score (improvement sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for multiple sclerosis (MS) type, region and baseline component assessments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint | 72 weeks | Estimated proportion of participants experiencing confirmed clinical worsening in 1 or more components of the multicomponent endpoint (EDSS, T25FW, 9HPT, or PASAT-3) over 72 weeks, defined as: a ≥1.0 point increase in EDSS from a baseline score of ≤5.5 or a ≥0.5 point increase from a baseline score equal to 6.0 (increase sustained for 3 months or greater); a ≥15%worsening from baseline in time to complete T25FW test (worsening sustained for 3 months or greater), where the time is the average of 2 trials at the same visit; a ≥15% worsening from baseline in time to complete 9HPT by either hand (worsening sustained for 3 months or greater for the same hand), where the time is the average of 2 trials for each hand at the same visit; a ≥15% worsening from baseline in PASAT-3 score (worsening sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for MS type, region and baseline component assessments. |
| Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Up to 84 weeks | An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the participant at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. |
| Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Up to 84 weeks | — |
Countries
Canada, Czechia, France, Hungary, Italy, Netherlands, Poland, Russia, Serbia, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 419 participants were randomized; 1 participant was not dosed.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo once every 4 weeks IV infusion up to Week 72.
Avonex once-weekly IM injection up to Week 84. | 93 |
| BIIB033, 3 mg/kg BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72.
Avonex once-weekly IM injection up to Week 84. | 45 |
| BIIB033, 10 mg/kg BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72.
Avonex once-weekly IM injection up to Week 84. | 95 |
| BIIB033, 30 mg/kg BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72.
Avonex once-weekly IM injection up to Week 84. | 93 |
| BIIB033, 100 mg/kg BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72.
Avonex once-weekly IM injection up to Week 84. | 92 |
| Total | 418 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 | 4 | 7 | 7 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Investigator Decision | 5 | 0 | 0 | 4 | 6 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 | 1 |
| Overall Study | Not Dosed | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 2 | 1 | 1 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 2 | 6 | 8 | 8 |
Baseline characteristics
| Characteristic | Placebo | BIIB033, 3 mg/kg | BIIB033, 10 mg/kg | BIIB033, 30 mg/kg | BIIB033, 100 mg/kg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 39.5 years STANDARD_DEVIATION 9.29 | 36.5 years STANDARD_DEVIATION 9.47 | 40.5 years STANDARD_DEVIATION 9.78 | 40.9 years STANDARD_DEVIATION 9.7 | 39.8 years STANDARD_DEVIATION 9.1 | 39.8 years STANDARD_DEVIATION 9.51 |
| Sex: Female, Male Female | 67 Participants | 24 Participants | 59 Participants | 61 Participants | 66 Participants | 277 Participants |
| Sex: Female, Male Male | 26 Participants | 21 Participants | 36 Participants | 32 Participants | 26 Participants | 141 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 74 / 93 | 38 / 45 | 79 / 95 | 70 / 93 | 67 / 92 |
| serious Total, serious adverse events | 13 / 93 | 4 / 45 | 11 / 95 | 20 / 93 | 16 / 92 |
Outcome results
Primary
Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint
Estimated proportion of participants experiencing confirmed improvement in any 1 or more of the following components: a ≥1 point decrease in the Expanded Disability Status Scale (EDSS) score from a baseline score of \<=6.0 (decrease sustained for ≥3 months); a ≥15% improvement from baseline in time to complete 9-Hole Peg Test (9HPT) by either hand (improvement sustained for ≥3 months for the same hand), where the time is the average time of 2 trials per hand at the same visit; a ≥15% improvement from baseline in time to complete Timed 25-Foot Walk (T25FW) test (improvement sustained for ≥3 months), where the time is the average time of 2 trials at the same visit; or a ≥15% improvement from baseline 3-Second Paced Auditory Serial Addition Test (PASAT-3) score (improvement sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for multiple sclerosis (MS) type, region and baseline component assessments.
Time frame: 72 weeks
Population: Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and included in the efficacy analysis (6 participants were excluded due to study site Good Clinical Practice deviation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint | 0.516 proportion of participants |
| BIIB033, 3 mg/kg | Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint | 0.511 proportion of participants |
| BIIB033, 10 mg/kg | Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint | 0.656 proportion of participants |
| BIIB033, 30 mg/kg | Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint | 0.688 proportion of participants |
| BIIB033, 100 mg/kg | Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint | 0.412 proportion of participants |
p-value: 0.958495% CI: [0.46, 2.07]Regression, Logistic
p-value: 0.063695% CI: [0.97, 3.31]Regression, Logistic
p-value: 0.02295% CI: [1.11, 3.84]Regression, Logistic
p-value: 0.177195% CI: [0.36, 1.21]Regression, Logistic
p-value: 0.8931Trend test
Secondary
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the participant at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above.
Time frame: Up to 84 weeks
Population: Safety Population: all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related event | 8 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Severe event | 7 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to withdrawal from study | 4 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to discontinuation of treatment | 4 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related serious event | 1 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related serious event | 1 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Moderate or severe event | 59 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Any event | 79 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Serious event | 13 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related event | 51 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Moderate or severe event | 26 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Any event | 39 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Severe event | 2 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related event | 8 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related event | 28 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Serious event | 4 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related serious event | 0 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related serious event | 0 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to discontinuation of treatment | 2 participants |
| BIIB033, 3 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to withdrawal from study | 2 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related event | 15 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related serious event | 0 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Any event | 84 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related event | 58 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Severe event | 6 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Moderate or severe event | 59 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Serious event | 11 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to discontinuation of treatment | 3 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to withdrawal from study | 4 participants |
| BIIB033, 10 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related serious event | 0 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related serious event | 1 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related serious event | 2 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Moderate or severe event | 59 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to withdrawal from study | 8 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to discontinuation of treatment | 7 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Any event | 79 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Serious event | 20 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related event | 54 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related event | 12 participants |
| BIIB033, 30 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Severe event | 6 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related serious event | 5 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related event | 16 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related event | 50 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Serious event | 16 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Any event | 73 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related serious event | 1 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to withdrawal from study | 7 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to discontinuation of treatment | 8 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Severe event | 7 participants |
| BIIB033, 100 mg/kg | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Moderate or severe event | 58 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Serious event | 51 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to withdrawal from study | 21 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Moderate or severe event | 202 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Severe event | 21 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related event | 190 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related serious event | 6 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | BIIB033/placebo-related event | 51 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Avonex-related serious event | 3 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Any event | 275 participants |
| BIIB033 Total | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | Event leading to discontinuation of treatment | 20 participants |
Secondary
Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84
Time frame: Up to 84 weeks
Population: PK Population: participants who received at least 1 dose of BIIB033 and had at least 1 serum concentration data point on record.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 72, postdose; n=38, 84, 69, 68 | 82.96 µg/mL | Standard Deviation 31.84 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 24, postdose; n=42, 92, 82, 76 | 144.12 µg/mL | Standard Deviation 373.36 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 48, postdose; n=42, 85, 75, 72 | 90.07 µg/mL | Standard Deviation 23.37 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 36, predose; n=41, 88, 79, 74 | 25.33 µg/mL | Standard Deviation 18.28 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 4, predose; n=45, 93, 91, 88 | 10.82 µg/mL | Standard Deviation 4.11 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 36, postdose; n=42, 88, 77, 73 | 94.62 µg/mL | Standard Deviation 21.89 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 48, predose; n=39, 85, 74, 70 | 20.78 µg/mL | Standard Deviation 6.26 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Baseline, predose; n=44, 95, 92, 92 | 0.00 µg/mL | Standard Deviation 0 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 4, postdose; n=45, 94, 89, 85 | 123.96 µg/mL | Standard Deviation 315.66 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 72, predose; n=41, 85, 72, 68 | 19.53 µg/mL | Standard Deviation 9.34 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 8, predose; n=45, 95, 89, 85 | 23.55 µg/mL | Standard Deviation 54.96 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 8, postdose; n=44, 94, 88, 79 | 86.29 µg/mL | Standard Deviation 52.74 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 84; n=40, 81, 69, 69 | 2.44 µg/mL | Standard Deviation 1.25 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 60, postdose; n=42, 84, 71, 71 | 93.11 µg/mL | Standard Deviation 35.98 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 16, predose; n=43, 94, 86, 79 | 19.96 µg/mL | Standard Deviation 9.74 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Baseline, postdose; n=44, 95, 91, 92 | 66.70 µg/mL | Standard Deviation 16 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 16, postdose; n=41, 93, 85, 78 | 85.95 µg/mL | Standard Deviation 29.04 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 60, predose; n=41, 84, 70, 68 | 21.29 µg/mL | Standard Deviation 12.34 |
| Placebo | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 24, predose; n=42, 93, 85, 74 | 36.41 µg/mL | Standard Deviation 85.48 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 24, predose; n=42, 93, 85, 74 | 77.88 µg/mL | Standard Deviation 33.68 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 8, predose; n=45, 95, 89, 85 | 65.48 µg/mL | Standard Deviation 52.53 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 24, postdose; n=42, 92, 82, 76 | 318.01 µg/mL | Standard Deviation 84.74 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 72, postdose; n=38, 84, 69, 68 | 313.13 µg/mL | Standard Deviation 87.22 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 84; n=40, 81, 69, 69 | 12.77 µg/mL | Standard Deviation 6.8 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 60, postdose; n=42, 84, 71, 71 | 335.10 µg/mL | Standard Deviation 93.29 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 36, predose; n=41, 88, 79, 74 | 85.05 µg/mL | Standard Deviation 44.67 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 60, predose; n=41, 84, 70, 68 | 81.77 µg/mL | Standard Deviation 30.24 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 48, predose; n=39, 85, 74, 70 | 80.28 µg/mL | Standard Deviation 31.62 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 8, postdose; n=44, 94, 88, 79 | 294.44 µg/mL | Standard Deviation 78.61 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 36, postdose; n=42, 88, 77, 73 | 339.17 µg/mL | Standard Deviation 88.96 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 4, predose; n=45, 93, 91, 88 | 46.28 µg/mL | Standard Deviation 33.15 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 48, postdose; n=42, 85, 75, 72 | 334.12 µg/mL | Standard Deviation 78.43 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 16, postdose; n=41, 93, 85, 78 | 309.38 µg/mL | Standard Deviation 83.38 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 72, predose; n=41, 85, 72, 68 | 78.94 µg/mL | Standard Deviation 29.95 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Baseline, postdose; n=44, 95, 91, 92 | 244.76 µg/mL | Standard Deviation 77.9 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 4, postdose; n=45, 94, 89, 85 | 279.67 µg/mL | Standard Deviation 100.01 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Baseline, predose; n=44, 95, 92, 92 | 0.01 µg/mL | Standard Deviation 0.13 |
| BIIB033, 3 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 16, predose; n=43, 94, 86, 79 | 71.80 µg/mL | Standard Deviation 25.13 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 72, predose; n=41, 85, 72, 68 | 215.09 µg/mL | Standard Deviation 62.98 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Baseline, predose; n=44, 95, 92, 92 | 7.79 µg/mL | Standard Deviation 74.75 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Baseline, postdose; n=44, 95, 91, 92 | 688.47 µg/mL | Standard Deviation 245.73 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 4, predose; n=45, 93, 91, 88 | 138.54 µg/mL | Standard Deviation 92.82 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 4, postdose; n=45, 94, 89, 85 | 784.08 µg/mL | Standard Deviation 204.31 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 8, predose; n=45, 95, 89, 85 | 195.29 µg/mL | Standard Deviation 118.24 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 8, postdose; n=44, 94, 88, 79 | 861.60 µg/mL | Standard Deviation 274.56 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 16, predose; n=43, 94, 86, 79 | 231.94 µg/mL | Standard Deviation 125.42 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 16, postdose; n=41, 93, 85, 78 | 881.45 µg/mL | Standard Deviation 211.32 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 24, predose; n=42, 93, 85, 74 | 230.46 µg/mL | Standard Deviation 77.4 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 24, postdose; n=42, 92, 82, 76 | 940.29 µg/mL | Standard Deviation 231.35 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 36, predose; n=41, 88, 79, 74 | 238.48 µg/mL | Standard Deviation 73.75 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 36, postdose; n=42, 88, 77, 73 | 197.86 µg/mL | Standard Deviation 197.96 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 48, predose; n=39, 85, 74, 70 | 272.88 µg/mL | Standard Deviation 167.79 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 48, postdose; n=42, 85, 75, 72 | 955.25 µg/mL | Standard Deviation 193.34 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 60, predose; n=41, 84, 70, 68 | 243.18 µg/mL | Standard Deviation 78.57 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 60, postdose; n=42, 84, 71, 71 | 939.17 µg/mL | Standard Deviation 255.64 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 72, postdose; n=38, 84, 69, 68 | 868.39 µg/mL | Standard Deviation 231.14 |
| BIIB033, 10 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 84; n=40, 81, 69, 69 | 46.16 µg/mL | Standard Deviation 31.52 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 72, postdose; n=38, 84, 69, 68 | 3145.82 µg/mL | Standard Deviation 1233.66 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 48, postdose; n=42, 85, 75, 72 | 3167.07 µg/mL | Standard Deviation 1144.25 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 16, postdose; n=41, 93, 85, 78 | 2921.09 µg/mL | Standard Deviation 1118.88 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 16, predose; n=43, 94, 86, 79 | 695.11 µg/mL | Standard Deviation 438.57 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Baseline, predose; n=44, 95, 92, 92 | 0.42 µg/mL | Standard Deviation 4.07 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 60, predose; n=41, 84, 70, 68 | 694.12 µg/mL | Standard Deviation 200.41 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 8, postdose; n=44, 94, 88, 79 | 2751.25 µg/mL | Standard Deviation 697.42 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 8, predose; n=45, 95, 89, 85 | 603.11 µg/mL | Standard Deviation 425.58 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 72, predose; n=41, 85, 72, 68 | 819.39 µg/mL | Standard Deviation 577.6 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 60, postdose; n=42, 84, 71, 71 | 3330.70 µg/mL | Standard Deviation 1076.88 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 4, postdose; n=45, 94, 89, 85 | 2763.26 µg/mL | Standard Deviation 823.42 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 4, predose; n=45, 93, 91, 88 | 457.96 µg/mL | Standard Deviation 308.09 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Baseline, postdose; n=44, 95, 91, 92 | 2298.20 µg/mL | Standard Deviation 712.91 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 36, postdose; n=42, 88, 77, 73 | 3048.66 µg/mL | Standard Deviation 989.34 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 36, predose; n=41, 88, 79, 74 | 725.22 µg/mL | Standard Deviation 344.01 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 84; n=40, 81, 69, 69 | 127.69 µg/mL | Standard Deviation 65.46 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 48, predose; n=39, 85, 74, 70 | 806.70 µg/mL | Standard Deviation 541.78 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 24, postdose; n=42, 92, 82, 76 | 2870.29 µg/mL | Standard Deviation 874.28 |
| BIIB033, 30 mg/kg | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 | Week 24, predose; n=42, 93, 85, 74 | 699.63 µg/mL | Standard Deviation 400.49 |
Secondary
Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint
Estimated proportion of participants experiencing confirmed clinical worsening in 1 or more components of the multicomponent endpoint (EDSS, T25FW, 9HPT, or PASAT-3) over 72 weeks, defined as: a ≥1.0 point increase in EDSS from a baseline score of ≤5.5 or a ≥0.5 point increase from a baseline score equal to 6.0 (increase sustained for 3 months or greater); a ≥15%worsening from baseline in time to complete T25FW test (worsening sustained for 3 months or greater), where the time is the average of 2 trials at the same visit; a ≥15% worsening from baseline in time to complete 9HPT by either hand (worsening sustained for 3 months or greater for the same hand), where the time is the average of 2 trials for each hand at the same visit; a ≥15% worsening from baseline in PASAT-3 score (worsening sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for MS type, region and baseline component assessments.
Time frame: 72 weeks
Population: Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and included in the efficacy analysis (6 participants were excluded due to study site Good Clinical Practice deviation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint | 0.403 proportion of participants |
| BIIB033, 3 mg/kg | Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint | 0.304 proportion of participants |
| BIIB033, 10 mg/kg | Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint | 0.509 proportion of participants |
| BIIB033, 30 mg/kg | Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint | 0.489 proportion of participants |
| BIIB033, 100 mg/kg | Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint | 0.369 proportion of participants |
p-value: 0.305895% CI: [0.28, 1.49]Regression, Logistic
p-value: 0.187395% CI: [0.81, 2.89]Regression, Logistic
p-value: 0.276695% CI: [0.76, 2.65]Regression, Logistic
p-value: 0.657895% CI: [0.45, 1.65]Regression, Logistic
p-value: 0.5255Trend test