Multiple Sclerosis
Conditions
Keywords
Remyelination, Re-myelination, DMT, LINGO-1, Anti-LINGO-1, Opicinumab
Brief summary
The primary objective of Part 1 of this study is to evaluate the effects of BIIB033 versus placebo on disability improvement over 72 weeks. The primary objective of Part 2 of this study is to evaluate the long-term safety profile of BIIB033 as an add-on therapy in participants with MS. The secondary objective of Part 1 is to evaluate the effects of BIIB033 versus placebo on additional measures of disability improvement. The secondary objective of Part 2 is to investigate long-term efficacy (disability improvement) and additional safety measures of BIIB033 as an add-on therapy in participants with MS.
Interventions
Administered as specified in the treatment arm
DRUGPlacebo
Administered as specified in the treatment arm
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 58 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Part 1 * Baseline Expanded Disability Status Scale (EDSS) of 2.0 to 6.0, have a diagnosis of relapsing-remitting multiple sclerosis (RRMS) per the 2010 McDonald's criteria or onset of secondary progressive multiple sclerosis (SPMS) per the Lublin and Reingold criteria, and should have experienced their first MS symptom(s) within the previous 20 years. * Subjects must have experienced at least 1 of the following within 24 months prior to Day 1/Baseline: a clinical relapse (but not within 24 weeks prior to Day 1/Baseline), gadolinium-enhancing lesions on brain or spinal cord magnetic resonance imaging (MRI), or new T2 lesion(s) on brain or spinal cord MRI. * Subjects must be on a stable dose of a protocol-specified anti-inflammatory disease-modifying therapy (DMT) (IFNβ \[Avonex, Plegridy, Betaferon/Betaseron, or Rebif\], dimethyl fumarate (DMF) \[Tecfidera\], or natalizumab \[Tysabri\]) for at least 24 weeks prior to enrollment. * In addition, subjects must have met protocol-defined MRI characteristics using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) sequences at Screening/Baseline. Key Inclusion Criteria: Part 2 -Subjects who complete study treatment (BIIB033 or placebo) at Part 1/Week 72 Visit. Key
Exclusion criteria
Part 1 * Primary progressive MS * An MS relapse that has occurred within 24 weeks prior to Day 1/Baseline or the subject has not stabilized from a previous relapse at the time of Screening. * Treatment with any chemotherapeutic agents (e.g., mitoxantrone, cyclophosphamide, cladribine), cell-depleting monoclonal antibodies (mAbs) (e.g., rituximab, ocrelizumab, alemtuzumab), total lymphoid irradiation, T-cell or T-cell receptor vaccination, or teriflunomide within 1 year prior to Day 1/Baseline. * Treatment with other anti-inflammatory DMTs (e.g., GA, fingolimod, daclizumab) or plasmapheresis within 24 weeks prior to Day1/Baseline. * Treatment with Botox for limb spasticity within 24 weeks before Day 1/Baseline. * Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to gadolinium renal impairment, or claustrophobia that cannot be medically managed. * History of human immunodeficiency virus or other immunodeficient conditions. * History of malignancy; however, subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study. Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Overall Response Score | Part 1: Baseline to Week 72 | Overall Response Score is a multicomponent score based on 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the nondominant hand (9HPT-ND). Overall Score was sum of 4 components at each visit and ranges from +4 (improvement) to -4 (worsening). At each visit, each component is given a score relative to baseline (BL): -1 if threshold is met for worsening, 0 if no changes meet threshold criteria, or +1 if threshold is met for improvement. For T25FW and 9HPT improvement is ≥15% decrease in time from BL and worsening is ≥15% increase in time from BL. For EDSS, improvement is: ≥1.0-point decrease in EDSS from a BL score of ≤6.0, and worsening is defined as a ≥1-point increase from a BL score of ≤5.5 or a ≥0.5-point increase from a BL score equal to 6.0. Positive Overall Response Score indicated that there was improvement in more components than there was worsening. |
| Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Part 2: Baseline to Week 169 | An AE is 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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and Without Confirmed Worsening in Any of the 4 Assessments During the 72 Weeks of the Study | Part 1: Baseline to Week 72 | EDSS measures disability status over time in MS on a scale ranging from 0 to 10, with higher scores indicating more disability. For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a BL score of ≤6.0, and worsening is defined as a ≥1-point increase from a BL score of ≤5.5 or a ≥0.5-point increase from a BL score equal to 6.0. T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet that is averaged between two completed trials. Longer time indicates slower walking. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. Longer time indicates poorer upper limb function. For T25FW and 9HPT ≥15% decrease in time from BL indicates improvement and ≥15% increase in time from BL indicates worsening. |
| Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit Modalities Test (SDMT) | Part 1: Baseline to Week 72 | EDSS measures disability status over time in MS on a scale (range 0-10), higher scores=more disability. For EDSS, improvement is: a ≥1.0-point decrease in EDSS from a BL score of ≤6.0. T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet that is averaged between two completed trials. Longer time=slower walking. 9HPT is quantitative test of upper extremity function that measures time it takes to place 9 pegs into 9 holes and then remove pegs. Longer time=poorer upper limb function. For T25FW and 9HPT ≥15% decrease in time from BL indicates improvement. The SDMT measures time to pair abstract geometric symbols with specific numbers. The score is the number of correctly coded items (range 0-110) in 90 seconds, higher scores=better outcome. Improvement is: ≥4-point increase from BL. |
| Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% Thresholds for T25FW and 9HPT) | Part 1: Baseline to Week 72 | EDSS measures disability status over time in MS on a scale ranging from 0 to 10, with higher scores indicating more disability. For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a BL score of ≤6.0. T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet that is averaged between two completed trials. Longer time indicates slower walking. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. Longer time indicates poorer upper limb function. For T25FW and 9HPT ≥15% decrease in time from BL indicates improvement. |
| Part 2: Overall Response Score | Part 2: Baseline to Week 96 | — |
| Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND | Part 2: Baseline to Week 108 | — |
| Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or PASAT-3 | Part 2: Baseline to Week 108 | — |
| Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and Without Confirmed Worsening in Any of the 4 Assessments During the 96 Weeks of the Study | Part 2: Baseline to Week 96 | — |
| Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND | Part 1: Baseline to Week 72 | EDSS measures disability status over time in MS on a scale ranging from 0 to 10, with higher scores indicating more disability. For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a BL score of ≤6.0. T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet that is averaged between two completed trials. Longer time indicates slower walking. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. Longer time indicates poorer upper limb function. For T25FW and 9HPT ≥15% decrease in time from BL indicates improvement. |
| Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% Thresholds for T25FW and 9HPT) | Part 2: Baseline to Week 108 | — |
| Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Part 2: Baseline to Week 96 | Laboratory assessments including hematology and blood chemistry were evaluated for safety. Criteria for abnormality: In 10\^9/liter (L) \[white blood cells \<3.0/\>16, neutrophils \<1.5/ \>13.5, lymphocytes \<0.8/ \>12, monocytes \>2.5, eosinophils \>1.6, basophils \>1.6, platelets \<=75/ \>=700\], hemoglobin \<=95 \[female (F)\] or \<=115 \[male (M)\] or \>=175 (F) or \>=190 (M) gram per liter (g/L), hematocrit \<=32 (F) or \<=37 (M) or \>=54 (F) or \>=60 (M) percentage (%), red blood cells \<=3.5/ \>=6.4 10\^12/L, in millimoles per liter (mmol/L) \[sodium \<=126/ \>=156, potassium \<=3/ \>=6, chloride \<=90/ \>=118, bicarbonate \<=16/ \>=35, calcium \<=2/ \>=3, phosphorous \<=0.5491/ \>=1.7119, glucose (non-fasting) \<=2.2/\>=13.75\], AST/SGOT \>=3x upper limit of normal (ULN), ALT/SGPT \>=3xULN, alkaline phosphatase \>=3xULN, creatinine \>=1.5xULN, total bilirubin \>=1.5xULN, total protein \<=45/ \>=100 g/L, albumin \<=25 g/L, uric acid \>=501.5 (F)/\>=619.5 (M) micromole (umol)/L |
| Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | Part 2: Baseline to Week 96 | The ECG result was classified as normal, abnormal, abnormal, not adverse event, or abnormal, adverse event. Shift to 'abnormal, not adverse event' included shift from normal or unknown to 'abnormal, not adverse event'. Shift to 'abnormal, adverse event' included shift from normal or unknown to 'abnormal, adverse event'. |
| Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Part 2: Baseline to Week 96 | Vital sign measurements including temperature, pulse rate (supine), systolic blood pressure (BP) and diastolic (supine) BP were evaluated for safety. Criteria for abnormalities: Temperature: \>38 degree celsius (◦C) or \>=1 ◦C increase from baseline (BL); Pulse: \[\>100 beats per minute (bpm) or increase from BL of \>30 bpm\] or (\<40 bpm or decrease from BL of \>20 bpm); Systolic BP: \[\>160 millimeters of mercury (mmHg)/increase from BL of \>40 mmHg\] or (\<90 mmHg/decrease from BL of \>30 mmHg); Diastolic BP: (\>100 mmHg/increase from BL of \>30 mmHg) or (\<45 mmHg/decrease from BL of \>20 mmHg). |
| Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | Part 2: Baseline, Week 12, 24, 36, 48, 72 and 96 | Criteria for abnormality was defined as a \>7% increase or decrease in weight at the specified time point. |
| Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Part 2: Baseline to Week 96 | C-SSRS systematically assess suicidal ideation and behavior rating scale. It rates an individual's degree of suicidal ideation on a scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent and behaviors. The scale identifies specific behaviors ranging from preparatory acts or behavior to suicide which may be indicative of an individual's intent to complete suicide. |
| Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and SDMT | Part 2: Baseline to Week 108 | — |
| Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced Auditory Serial Addition Test (PASAT-3) | Part 1: Baseline to Week 72 | EDSS measures disability status over time in MS (scale range: 0-10), higher scores=more disability and improvement defined as ≥1.0-point decrease in EDSS from BL score ≤6.0. T25FW is quantitative mobility and leg function performance test, where timed walk over 25 feet that is averaged between two completed trials. Longer time=slower walking. 9HPT is quantitative test of upper extremity function, measures time to place 9 pegs into 9 holes and then remove pegs. Longer time=poorer upper limb function. PASAT assesses auditory information processing speed. In 3-second PASAT, numbers are presented at a rate of 1 every 3 seconds with scores (range 0-120), higher scores=better working memory. For T25FW and 9HPT ≥15% decrease in time from BL is improvement. For PASAT ≥15% increase from BL is improvement. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at the investigative sites in the Australia, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom and United States from 15 November 2017 to 12 February 2021.
Pre-assignment details
A total of 263 participants with relapsing multiple sclerosis (RMS) were randomized in Part 1 (Placebo-controlled) of the study to receive BIIB033 or placebo. Participants who completed Part 1 and were eligible were enrolled into Part 2 (Open-label) of the study to receive BIIB033. Part 2 of the study was terminated early based on Sponsor's decision.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo Participants with RMS received placebo IV as an add-on therapy to a background DMT once every 4 weeks over 72 weeks. | 131 |
| Part 1: BIIB033 750 mg Participants with RMS received BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks over 72 weeks. | 132 |
| Total | 263 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1 (Week 0 to Week 72) | Adverse Event | 3 | 0 | 0 | 0 |
| Part 1 (Week 0 to Week 72) | Consent Withdrawn | 12 | 9 | 0 | 0 |
| Part 1 (Week 0 to Week 72) | Death | 0 | 1 | 0 | 0 |
| Part 1 (Week 0 to Week 72) | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Part 1 (Week 0 to Week 72) | Other | 8 | 2 | 0 | 0 |
| Part 1 (Week 0 to Week 72) | Pregnancy | 0 | 1 | 0 | 0 |
| Part 2 (Week 73 to Week 168) | Adverse Event | 0 | 0 | 2 | 0 |
| Part 2 (Week 73 to Week 168) | Consent Withdrawn | 0 | 0 | 10 | 11 |
| Part 2 (Week 73 to Week 168) | Investigator Decision | 0 | 0 | 2 | 1 |
| Part 2 (Week 73 to Week 168) | Other | 0 | 0 | 84 | 100 |
| Part 2 (Week 73 to Week 168) | Participants Not Dosed | 0 | 0 | 1 | 0 |
| Part 2 (Week 73 to Week 168) | Pregnancy | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Part 1: BIIB033 750 mg | Part 1: Placebo |
|---|---|---|---|
| Age, Continuous | 38.6 years STANDARD_DEVIATION 9.2 | 39.4 years STANDARD_DEVIATION 9.12 | 37.7 years STANDARD_DEVIATION 9.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 13 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 239 Participants | 116 Participants | 123 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 240 Participants | 118 Participants | 122 Participants |
| Sex: Female, Male Female | 169 Participants | 90 Participants | 79 Participants |
| Sex: Female, Male Male | 94 Participants | 42 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 131 | 1 / 132 | 0 / 100 | 0 / 113 |
| other Total, other adverse events | 91 / 131 | 93 / 132 | 34 / 100 | 46 / 113 |
| serious Total, serious adverse events | 6 / 131 | 9 / 132 | 9 / 100 | 2 / 113 |
Outcome results
Primary
Part 1: Overall Response Score
Overall Response Score is a multicomponent score based on 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the nondominant hand (9HPT-ND). Overall Score was sum of 4 components at each visit and ranges from +4 (improvement) to -4 (worsening). At each visit, each component is given a score relative to baseline (BL): -1 if threshold is met for worsening, 0 if no changes meet threshold criteria, or +1 if threshold is met for improvement. For T25FW and 9HPT improvement is ≥15% decrease in time from BL and worsening is ≥15% increase in time from BL. For EDSS, improvement is: ≥1.0-point decrease in EDSS from a BL score of ≤6.0, and worsening is defined as a ≥1-point increase from a BL score of ≤5.5 or a ≥0.5-point increase from a BL score equal to 6.0. Positive Overall Response Score indicated that there was improvement in more components than there was worsening.
Time frame: Part 1: Baseline to Week 72
Population: ITT population included all randomized participants who received at least 1 dose of study treatment. Participants were analyzed according to their treatment assignment regardless of actual treatment received.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1: Placebo | Part 1: Overall Response Score | -0.04 score on a scale |
| Part 1: BIIB033 750 mg | Part 1: Overall Response Score | 0.11 score on a scale |
Comparison: Over 72 weeks: Overall Response Scorep-value: 0.147995% CI: [-0.05, 0.35]MMRM
Primary
Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is 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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
Time frame: Part 2: Baseline to Week 169
Population: Safety population included all participants who received at least 1 dose of study treatment. Participants were analyzed based on the actual treatment allocation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 71 Participants |
| Part 1: Placebo | Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 9 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 76 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
Secondary
Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit Modalities Test (SDMT)
EDSS measures disability status over time in MS on a scale (range 0-10), higher scores=more disability. For EDSS, improvement is: a ≥1.0-point decrease in EDSS from a BL score of ≤6.0. T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet that is averaged between two completed trials. Longer time=slower walking. 9HPT is quantitative test of upper extremity function that measures time it takes to place 9 pegs into 9 holes and then remove pegs. Longer time=poorer upper limb function. For T25FW and 9HPT ≥15% decrease in time from BL indicates improvement. The SDMT measures time to pair abstract geometric symbols with specific numbers. The score is the number of correctly coded items (range 0-110) in 90 seconds, higher scores=better outcome. Improvement is: ≥4-point increase from BL.
Time frame: Part 1: Baseline to Week 72
Population: ITT population included all randomized participants who received at least 1 dose of study treatment. Participants were analyzed according to their treatment assignment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit Modalities Test (SDMT) | 63 percentage of participants |
| Part 1: BIIB033 750 mg | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit Modalities Test (SDMT) | 75 percentage of participants |
p-value: 0.041795% CI: [1.02, 3.11]Regression, Logistic
Secondary
Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced Auditory Serial Addition Test (PASAT-3)
EDSS measures disability status over time in MS (scale range: 0-10), higher scores=more disability and improvement defined as ≥1.0-point decrease in EDSS from BL score ≤6.0. T25FW is quantitative mobility and leg function performance test, where timed walk over 25 feet that is averaged between two completed trials. Longer time=slower walking. 9HPT is quantitative test of upper extremity function, measures time to place 9 pegs into 9 holes and then remove pegs. Longer time=poorer upper limb function. PASAT assesses auditory information processing speed. In 3-second PASAT, numbers are presented at a rate of 1 every 3 seconds with scores (range 0-120), higher scores=better working memory. For T25FW and 9HPT ≥15% decrease in time from BL is improvement. For PASAT ≥15% increase from BL is improvement.
Time frame: Part 1: Baseline to Week 72
Population: ITT population included all randomized participants who received at least 1 dose of study treatment. Participants were analyzed according to their treatment assignment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced Auditory Serial Addition Test (PASAT-3) | 60 percentage of participants |
| Part 1: BIIB033 750 mg | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced Auditory Serial Addition Test (PASAT-3) | 52 percentage of participants |
p-value: 0.213195% CI: [0.41, 1.22]Regression, Logistic
Secondary
Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND
EDSS measures disability status over time in MS on a scale ranging from 0 to 10, with higher scores indicating more disability. For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a BL score of ≤6.0. T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet that is averaged between two completed trials. Longer time indicates slower walking. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. Longer time indicates poorer upper limb function. For T25FW and 9HPT ≥15% decrease in time from BL indicates improvement.
Time frame: Part 1: Baseline to Week 72
Population: ITT population included all randomized participants who received at least 1 dose of study treatment. Participants were analyzed according to their treatment assignment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND | 37 percentage of participants |
| Part 1: BIIB033 750 mg | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND | 39 percentage of participants |
p-value: 0.768295% CI: [0.65, 1.79]Regression, Logistic
Secondary
Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% Thresholds for T25FW and 9HPT)
EDSS measures disability status over time in MS on a scale ranging from 0 to 10, with higher scores indicating more disability. For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a BL score of ≤6.0. T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet that is averaged between two completed trials. Longer time indicates slower walking. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. Longer time indicates poorer upper limb function. For T25FW and 9HPT ≥15% decrease in time from BL indicates improvement.
Time frame: Part 1: Baseline to Week 72
Population: ITT population included all randomized participants who received at least 1 dose of study treatment. Participants were analyzed according to their treatment assignment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% Thresholds for T25FW and 9HPT) | 25 percentage of participants |
| Part 1: BIIB033 750 mg | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% Thresholds for T25FW and 9HPT) | 32 percentage of participants |
p-value: 0.290895% CI: [0.78, 2.33]Regression, Logistic
Secondary
Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and Without Confirmed Worsening in Any of the 4 Assessments During the 72 Weeks of the Study
EDSS measures disability status over time in MS on a scale ranging from 0 to 10, with higher scores indicating more disability. For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a BL score of ≤6.0, and worsening is defined as a ≥1-point increase from a BL score of ≤5.5 or a ≥0.5-point increase from a BL score equal to 6.0. T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet that is averaged between two completed trials. Longer time indicates slower walking. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. Longer time indicates poorer upper limb function. For T25FW and 9HPT ≥15% decrease in time from BL indicates improvement and ≥15% increase in time from BL indicates worsening.
Time frame: Part 1: Baseline to Week 72
Population: ITT population included all randomized participants who received at least 1 dose of study treatment. Participants were analyzed according to their treatment assignment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and Without Confirmed Worsening in Any of the 4 Assessments During the 72 Weeks of the Study | 31 percentage of participants |
| Part 1: BIIB033 750 mg | Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and Without Confirmed Worsening in Any of the 4 Assessments During the 72 Weeks of the Study | 28 percentage of participants |
p-value: 0.465495% CI: [0.47, 1.41]Regression, Logistic
Secondary
Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit
C-SSRS systematically assess suicidal ideation and behavior rating scale. It rates an individual's degree of suicidal ideation on a scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent and behaviors. The scale identifies specific behaviors ranging from preparatory acts or behavior to suicide which may be indicative of an individual's intent to complete suicide.
Time frame: Part 2: Baseline to Week 96
Population: Safety population included all participants who received at least 1 dose of study treatment. Participants were analyzed based on the actual treatment allocation. 'Number Analyzed' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Wish to be Dead | 2 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Non-specific Active Suicidal Thoughts | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Active Suicidal Ideation with any Methods (not Plan) Without Intent to act | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Active Suicidal Ideation with Some Intent to act, Without Specific Plan | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Active Suicidal Ideation with Specific Plan and Intent | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Preparatory Acts or Behavior | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Aborted Attempt | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Interrupted Attempt | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Actual Attempt | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Suicidal Behavior | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Suicide | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Self-injurious Behavior Without Suicidal Intent | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Suicide | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Wish to be Dead | 3 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Aborted Attempt | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Non-specific Active Suicidal Thoughts | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Suicidal Behavior | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Active Suicidal Ideation with any Methods (not Plan) Without Intent to act | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Interrupted Attempt | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Active Suicidal Ideation with Some Intent to act, Without Specific Plan | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Self-injurious Behavior Without Suicidal Intent | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Ideation: Active Suicidal Ideation with Specific Plan and Intent | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Actual Attempt | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit | Suicidal Behavior: Preparatory Acts or Behavior | 1 Participants |
Secondary
Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values
Laboratory assessments including hematology and blood chemistry were evaluated for safety. Criteria for abnormality: In 10\^9/liter (L) \[white blood cells \<3.0/\>16, neutrophils \<1.5/ \>13.5, lymphocytes \<0.8/ \>12, monocytes \>2.5, eosinophils \>1.6, basophils \>1.6, platelets \<=75/ \>=700\], hemoglobin \<=95 \[female (F)\] or \<=115 \[male (M)\] or \>=175 (F) or \>=190 (M) gram per liter (g/L), hematocrit \<=32 (F) or \<=37 (M) or \>=54 (F) or \>=60 (M) percentage (%), red blood cells \<=3.5/ \>=6.4 10\^12/L, in millimoles per liter (mmol/L) \[sodium \<=126/ \>=156, potassium \<=3/ \>=6, chloride \<=90/ \>=118, bicarbonate \<=16/ \>=35, calcium \<=2/ \>=3, phosphorous \<=0.5491/ \>=1.7119, glucose (non-fasting) \<=2.2/\>=13.75\], AST/SGOT \>=3x upper limit of normal (ULN), ALT/SGPT \>=3xULN, alkaline phosphatase \>=3xULN, creatinine \>=1.5xULN, total bilirubin \>=1.5xULN, total protein \<=45/ \>=100 g/L, albumin \<=25 g/L, uric acid \>=501.5 (F)/\>=619.5 (M) micromole (umol)/L
Time frame: Part 2: Baseline to Week 96
Population: Safety population included all participants who received at least 1 dose of study treatment. Participants were analyzed based on the actual treatment allocation. 'Number Analyzed' signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Potassium (mmol/L): >=6 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Hemoglobin (g/L): >=175 (F) or >=190 (M) | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Chloride (mmol/L): <=90 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Lymphocytes (10^9/L): >12 | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Chloride (mmol/L): >=118 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Hematocrit (%): <=32 (F) or <=37 (M) | 2 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Bicarbonate (mmol/L): <=16 | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | White blood cells (10^9/L): >16 | 2 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Bicarbonate (mmol/L): >=35 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Hematocrit (%): >=54 (F) or >=60 (M) | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Calcium (mmol/L): <=2 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Monocytes (10^9/L): >2.5 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Calcium (mmol/L): >=3 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Red blood cells (10^12/L): <=3.5 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Phosphorus (mmol/L): <=0.5491 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Neutrophils (10^9/L): >13.5 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Phosphorus (mmol/L): >=1.7119 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Red blood cells (10^12/L): >=6.4 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT): >=3xULN | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Eosinophils (10^9/L): >1.6 | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT): >=3xULN | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Platelets (10^9/L): <=75 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Alkaline phosphatase: >=3xULN | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | White blood cells [10^9/L]: <3.0 | 3 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Creatinine: >=1.5xULN | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Basophils (10^9/L): >1.6 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Total bilirubin: >=1.5xULN | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Sodium (mmol/L): <=126 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Total protein (g/L): <=45 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Lymphocytes (10^9/L): <0.8 | 13 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Total protein (g/L): >=100 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Sodium (mmol/L): >=156 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Albumin (g/L): <=25 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Hemoglobin (g/L): <=95 (F) or <=115 (M) | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Uric acid (umol)/L: >=501.5 (F) or >=619.5 (M) | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Potassium (mmol/L): <=3 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Glucose (non-fasting) (mmol/L): <=2.2 | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Neutrophils (10^9/L): <1.5 | 3 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Glucose (non-fasting) (mmol/L): >=13.75 | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Platelets (10^9/L): >=700 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Glucose (non-fasting) (mmol/L): >=13.75 | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | White blood cells [10^9/L]: <3.0 | 3 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | White blood cells (10^9/L): >16 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Neutrophils (10^9/L): <1.5 | 3 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Neutrophils (10^9/L): >13.5 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Lymphocytes (10^9/L): <0.8 | 15 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Lymphocytes (10^9/L): >12 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Monocytes (10^9/L): >2.5 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Eosinophils (10^9/L): >1.6 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Basophils (10^9/L): >1.6 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Hemoglobin (g/L): <=95 (F) or <=115 (M) | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Hemoglobin (g/L): >=175 (F) or >=190 (M) | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Hematocrit (%): <=32 (F) or <=37 (M) | 5 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Hematocrit (%): >=54 (F) or >=60 (M) | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Red blood cells (10^12/L): <=3.5 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Red blood cells (10^12/L): >=6.4 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Platelets (10^9/L): <=75 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Platelets (10^9/L): >=700 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Sodium (mmol/L): <=126 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Sodium (mmol/L): >=156 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Potassium (mmol/L): <=3 | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Potassium (mmol/L): >=6 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Chloride (mmol/L): <=90 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Chloride (mmol/L): >=118 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Bicarbonate (mmol/L): <=16 | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Bicarbonate (mmol/L): >=35 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Calcium (mmol/L): <=2 | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Calcium (mmol/L): >=3 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Phosphorus (mmol/L): <=0.5491 | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Phosphorus (mmol/L): >=1.7119 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT): >=3xULN | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT): >=3xULN | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Alkaline phosphatase: >=3xULN | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Creatinine: >=1.5xULN | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Total bilirubin: >=1.5xULN | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Total protein (g/L): <=45 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Total protein (g/L): >=100 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Albumin (g/L): <=25 | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Uric acid (umol)/L: >=501.5 (F) or >=619.5 (M) | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values | Glucose (non-fasting) (mmol/L): <=2.2 | 0 Participants |
Secondary
Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values
The ECG result was classified as normal, abnormal, abnormal, not adverse event, or abnormal, adverse event. Shift to 'abnormal, not adverse event' included shift from normal or unknown to 'abnormal, not adverse event'. Shift to 'abnormal, adverse event' included shift from normal or unknown to 'abnormal, adverse event'.
Time frame: Part 2: Baseline to Week 96
Population: Safety population included all participants who received at least 1 dose of study treatment. Participants were analyzed based on the actual treatment allocation. 'Number Analyzed' signifies number of participants analyzed at the specified timepoint for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 96: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 24: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 48: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 60: Shift to Abnormal, not Adverse Event | 3 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 72: Shift to Abnormal, not Adverse Event | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 84: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 96: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 12: Normal | 80 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 12: Abnormal, not Adverse Event | 9 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 12: Abnormal, Adverse Event | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 24: Shift to Abnormal, not Adverse Event | 4 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 24: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 36: Shift to Abnormal, not Adverse Event | 4 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 36: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 48: Shift to Abnormal, not Adverse Event | 3 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 48: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 60: Shift to Abnormal, not Adverse Event | 5 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 72: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 84: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 96: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 96: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 24: Normal | 83 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 24: Abnormal, not Adverse Event | 6 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 36: Shift to Abnormal, not Adverse Event | 5 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 36: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 48: Shift to Abnormal, not Adverse Event | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 48: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 60: Shift to Abnormal, not Adverse Event | 4 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 72: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 84: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 96: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 96: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 36: Normal | 77 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 36: Abnormal, not Adverse Event | 7 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 36: Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 48: Shift to Abnormal, not Adverse Event | 3 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 48: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 60: Shift to Abnormal, not Adverse Event | 6 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 84: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 96: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 96: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 48: Normal | 74 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 48: Abnormal, not Adverse Event | 4 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 48: Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 60: Shift to Abnormal, not Adverse Event | 4 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 72: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 84: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 96: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 96: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 60: Normal | 53 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 60: Abnormal, not Adverse Event | 6 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 72: Shift to Abnormal, not Adverse Event | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 96: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 72: Normal | 26 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 72: Abnormal, not Adverse Event | 2 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 72 to Week 84: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 72 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 72 to Week 96: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 72 to Week 96: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 84: Normal | 7 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 84: Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 84 to Week 96: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 84 to Week 96: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 96: Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 72: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 84: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 96: Shift to Abnormal, not Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 96: Normal | 3 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Day 1: Normal | 83 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Day 1: Abnormal, not Adverse Event | 10 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 12: Shift to Abnormal, not Adverse Event | 7 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 12: Shift to Abnormal, Adverse Event | 1 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 24: Shift to Abnormal, not Adverse Event | 4 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 36: Shift to Abnormal, not Adverse Event | 3 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 36: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: Placebo | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 48: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 24: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 72: Shift to Abnormal, not Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 24: Abnormal, not Adverse Event | 20 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 84: Abnormal, not Adverse Event | 3 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 36: Shift to Abnormal, not Adverse Event | 4 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 84: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 72: Abnormal, not Adverse Event | 4 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 36: Shift to Abnormal, Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 60: Normal | 52 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 48: Shift to Abnormal, not Adverse Event | 5 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Day 1: Normal | 89 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 48: Normal | 76 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Day 1: Abnormal, not Adverse Event | 16 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 48: Shift to Abnormal, Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 12: Shift to Abnormal, not Adverse Event | 6 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 96: Normal | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 12: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 60: Shift to Abnormal, not Adverse Event | 3 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 48: Abnormal, not Adverse Event | 15 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 36: Shift to Abnormal, not Adverse Event | 10 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 36: Shift to Abnormal, Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 60: Abnormal, not Adverse Event | 10 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 48: Shift to Abnormal, not Adverse Event | 7 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 48: Shift to Abnormal, Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 48: Abnormal, Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 60: Shift to Abnormal, not Adverse Event | 5 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 84: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 72 to Week 84: Shift to Abnormal, not Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 72: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 24 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 60: Shift to Abnormal, not Adverse Event | 4 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 84: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 72: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Day 1 to Week 24: Shift to Abnormal, not Adverse Event | 8 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 36: Normal | 80 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 12: Normal | 81 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 84: Normal | 7 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 12: Abnormal, not Adverse Event | 16 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 36: Abnormal, not Adverse Event | 20 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 12: Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 72: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 24: Shift to Abnormal, not Adverse Event | 7 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 36: Abnormal, Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 24: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 60 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 36: Shift to Abnormal, not Adverse Event | 8 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 48: Shift to Abnormal, not Adverse Event | 3 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 36: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 48: Shift to Abnormal, not Adverse Event | 6 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 48: Shift to Abnormal, Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 48: Shift to Abnormal, Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 72 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 60: Shift to Abnormal, not Adverse Event | 5 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 60: Shift to Abnormal, not Adverse Event | 5 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 84: Shift to Abnormal, not Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 72: Shift to Abnormal, not Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 60: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 72: Shift to Abnormal, not Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 84: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 96: Abnormal, not Adverse Event | 1 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 12 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 72: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 48 to Week 84: Shift to Abnormal, Adverse Event | 0 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | From Week 36 to Week 84: Shift to Abnormal, not Adverse Event | 2 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 24: Normal | 83 Participants |
| Part 1: BIIB033 750 mg | Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values | At Week 72: Normal | 24 Participants |
Secondary
Part 2: Overall Response Score
Time frame: Part 2: Baseline to Week 96
Population: Part 1 of Study 215MS202 failed to meet its primary endpoint of ORS over 72 weeks. Trial also failed to show efficacy in its secondary endpoints. Thus, Sponsor decided to terminate Part 2 of study early, and no participants had the opportunity to complete Part 2 of the study. No data was collected as per the protocol prespecified Part 2 efficacy analyses to assess the long-term efficacy of BIIB033 in Part 2.
Secondary
Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and SDMT
Time frame: Part 2: Baseline to Week 108
Population: Part 1 of Study 215MS202 failed to meet its primary endpoint of ORS over 72 weeks. Trial also failed to show efficacy in its secondary endpoints. Thus, Sponsor decided to terminate Part 2 of study early, and no participants had the opportunity to complete Part 2 of the study. No data was collected as per the protocol prespecified Part 2 efficacy analyses to assess the long-term efficacy of BIIB033 in Part 2.
Secondary
Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or PASAT-3
Time frame: Part 2: Baseline to Week 108
Population: Part 1 of Study 215MS202 failed to meet its primary endpoint of ORS over 72 weeks. Trial also failed to show efficacy in its secondary endpoints. Thus, Sponsor decided to terminate Part 2 of study early, and no participants had the opportunity to complete Part 2 of the study. No data was collected as per the protocol prespecified Part 2 efficacy analyses to assess the long-term efficacy of BIIB033 in Part 2.
Secondary
Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND
Time frame: Part 2: Baseline to Week 108
Population: Part 1 of Study 215MS202 failed to meet its primary endpoint of ORS over 72 weeks. Trial also failed to show efficacy in its secondary endpoints. Thus, Sponsor decided to terminate Part 2 of study early, and no participants had the opportunity to complete Part 2 of the study. No data was collected as per the protocol prespecified Part 2 efficacy analyses to assess the long-term efficacy of BIIB033 in Part 2.
Secondary
Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% Thresholds for T25FW and 9HPT)
Time frame: Part 2: Baseline to Week 108
Population: Part 1 of Study 215MS202 failed to meet its primary endpoint of ORS over 72 weeks. Trial also failed to show efficacy in its secondary endpoints. Thus, Sponsor decided to terminate Part 2 of study early, and no participants had the opportunity to complete Part 2 of the study. No data was collected as per the protocol prespecified Part 2 efficacy analyses to assess the long-term efficacy of BIIB033 in Part 2.
Secondary
Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and Without Confirmed Worsening in Any of the 4 Assessments During the 96 Weeks of the Study
Time frame: Part 2: Baseline to Week 96
Population: Part 1 of Study 215MS202 failed to meet its primary endpoint of ORS over 72 weeks. Trial also failed to show efficacy in its secondary endpoints. Thus, Sponsor decided to terminate Part 2 of study early, and no participants had the opportunity to complete Part 2 of the study. No data was collected as per the protocol prespecified Part 2 efficacy analyses to assess the long-term efficacy of BIIB033 in Part 2.
Secondary
Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
Vital sign measurements including temperature, pulse rate (supine), systolic blood pressure (BP) and diastolic (supine) BP were evaluated for safety. Criteria for abnormalities: Temperature: \>38 degree celsius (◦C) or \>=1 ◦C increase from baseline (BL); Pulse: \[\>100 beats per minute (bpm) or increase from BL of \>30 bpm\] or (\<40 bpm or decrease from BL of \>20 bpm); Systolic BP: \[\>160 millimeters of mercury (mmHg)/increase from BL of \>40 mmHg\] or (\<90 mmHg/decrease from BL of \>30 mmHg); Diastolic BP: (\>100 mmHg/increase from BL of \>30 mmHg) or (\<45 mmHg/decrease from BL of \>20 mmHg).
Time frame: Part 2: Baseline to Week 96
Population: Safety population included all participants who received at least 1 dose of study treatment. Participants were analyzed based on the actual treatment allocation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Systolic BP: (>160 mmHg/increase from BL of >40 mmHg) or (<90 mmHg/decrease from BL of >30 mmHg) | 8 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Temperature: >38 ◦C or >=1 ◦C Increase From BL | 4 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Pulse: (>100 bpm or increase from BL of >30 bpm) or (<40 bpm or decrease from BL of >20 bpm) | 22 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Pulse: >100 bpm or >30 bpm increase from BL | 11 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Pulse: <40 bpm or >20 bpm decrease from BL | 13 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Systolic BP: >160 mmHg or >40 mmHg increase from BL | 4 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Systolic BP: <90 mmHg or >30 mmHg decrease from BL | 4 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Diastolic BP: (>100 mmHg/increase from BL of >30 mmHg) or (<45 mmHg/decrease from BL of >20 mmHg) | 13 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Diastolic BP: >100 mmHg or >30 mmHg increase from BL | 3 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Diastolic BP: <45 mmHg or >20 mmHg decrease from BL | 11 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Diastolic BP: (>100 mmHg/increase from BL of >30 mmHg) or (<45 mmHg/decrease from BL of >20 mmHg) | 9 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Systolic BP: >160 mmHg or >40 mmHg increase from BL | 4 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Temperature: >38 ◦C or >=1 ◦C Increase From BL | 5 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Diastolic BP: <45 mmHg or >20 mmHg decrease from BL | 5 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Pulse: (>100 bpm or increase from BL of >30 bpm) or (<40 bpm or decrease from BL of >20 bpm) | 25 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Systolic BP: <90 mmHg or >30 mmHg decrease from BL | 8 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Pulse: >100 bpm or >30 bpm increase from BL | 15 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Diastolic BP: >100 mmHg or >30 mmHg increase from BL | 4 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Pulse: <40 bpm or >20 bpm decrease from BL | 11 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Systolic BP: (>160 mmHg/increase from BL of >40 mmHg) or (<90 mmHg/decrease from BL of >30 mmHg) | 10 percentage of participants |
Secondary
Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values
Criteria for abnormality was defined as a \>7% increase or decrease in weight at the specified time point.
Time frame: Part 2: Baseline, Week 12, 24, 36, 48, 72 and 96
Population: Safety population included all participants who received at least 1 dose of study treatment. Participants were analyzed based on the actual treatment allocation. 'Number Analyzed' signifies number of participants analyzed at the specified timepoint for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Baseline with Increase >7% | 27 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Baseline with Decrease >7% | 4 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 12 with Increase >7% | 4 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 12 with Decrease >7% | 1 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 24 with Increase >7% | 10 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 24 with Decrease >7% | 1 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 36 with Increase >7% | 18 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 36 with Decrease >7% | 1 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 48 with Increase >7% | 20 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 48 with Decrease >7% | 0 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 72 with Increase >7% | 19 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 72 with Decrease >7% | 3 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 96 with Increase >7% | 30 percentage of participants |
| Part 1: Placebo | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 96 with Decrease >7% | 4 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 72 with Increase >7% | 15 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Baseline with Increase >7% | 15 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 36 with Decrease >7% | 7 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Baseline with Decrease >7% | 15 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 96 with Increase >7% | 13 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 12 with Increase >7% | 3 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 48 with Increase >7% | 8 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 12 with Decrease >7% | 2 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 72 with Decrease >7% | 12 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 24 with Increase >7% | 10 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 48 with Decrease >7% | 10 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 24 with Decrease >7% | 5 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 96 with Decrease >7% | 16 percentage of participants |
| Part 1: BIIB033 750 mg | Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values | At Week 36 with Increase >7% | 5 percentage of participants |