Efficacy and Safety of BIIB033 (Opicinumab) as an Add-on... | NCT03222973

ID	Type	Description	Link
2017-001224-22	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BIIB033 (opicinumab) 750 mg	Experimental	Participants with relapsing multiple sclerosis (RMS) will receive BIIB033 750 milligram (mg) intravenously (IV) as an add-on therapy to a background disease-modifying therapy (DMT) once every 4 weeks over 72 weeks in Part 1 and once every 4 weeks over 96 weeks in Part 2.	Drug: BIIB033 (opicinumab)
Placebo	Placebo Comparator	Participants with RMS will receive placebo IV as an add-on therapy to a background DMT once every 4 weeks over 72 weeks in Part 1 and BIIB033 once every 4 weeks over 96 weeks in Part 2. The placebo looks like BIIB033 but does not contain the active ingredient that is thought to have an effect on MS disease. The placebo used in this study is sterile normal saline (water with a small amount of sodium chloride [salt]).	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
BIIB033 (opicinumab)	Drug	Administered as specified in the treatment arm	BIIB033 (opicinumab) 750 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Part 1: Baseline to Week 72
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.	Part 2: Baseline to Week 169

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility 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 Exclusion Criteria: Part 2

Subjects who did not complete study treatment in Part 1/Week 72 Visit
Subjects who have a duration >12 weeks between their Part 1/Week 72 Visit and Part 2/Day 1.
Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to Gd, renal impairment, or claustrophobia that cannot be medically managed.
History of human immunodeficiency virus or other immunodeficient conditions not related to DMT treatment.
History of malignancy unless enrollment is approved by the Sponsor; 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Name	Affiliation	Role
Medical Director	Biogen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Cullman	Alabama	35058	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
41454463	Derived	Calabresi PA, Giovannoni G, Hartung HP, Naismith RT, Fox RJ, Sormani MP, Arnold DL, Kappos L, Valis M, Newsome SD, Belkin MI, Bartholome E, Riester K, Javor A, Lyons J, Bradley DP, Fisher E, Tagge I, Naylor ML, Belachew S, Deykin A, Franchimont N, Zhu B, Cheng W. Safety and efficacy of opicinumab in participants with relapsing multiple sclerosis (AFFINITY Part 1): A randomized, controlled, phase 2 trial. Mult Scler. 2026 Jan;32(1):107-120. doi: 10.1177/13524585251396433. Epub 2025 Dec 26.
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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1: Placebo	Participants with RMS received placebo intravenously (IV) as an add-on therapy to a background disease-modifying therapy (DMT) once every 4 weeks over 72 weeks.
FG001	Part 1: BIIB033 750 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 13, 2019	Mar 31, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Mean

95% Confidence Interval

score on a scale

Part 1: Baseline to Week 72

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000131 OG001132

Title

Denominators

Categories

Title	Measurements
	OG000-0.04(-0.18 to 0.11) OG0010.11(-0.03 to 0.25)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Over 72 weeks: Overall Response Score	MMRM		0.1479	P-values are based on the Mixed Model for Repeated Measures (MMRM) adjusted for background DMT group, baseline magnetization transfer ratio (MTR)/diffusion tensor imaging (DTI) category and baseline component assessments.	Treatment Difference	0.15			2-Sided	95	-0.05	0.35					Superiority

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.

Safety population included all participants who received at least 1 dose of study treatment. Participants were analyzed based on the actual treatment allocation.

Posted

Count of Participants

Participants

Part 2: Baseline to Week 169

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

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.

Posted

Number

percentage of participants

Part 1: Baseline to Week 72

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Number

percentage of participants

Part 1: Baseline to Week 72

ID	Title	Description
OG000	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.
OG001	Part 1: BIIB033 750 mg

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.

Posted

Number

percentage of participants

Part 1: Baseline to Week 72

ID	Title	Description
OG000	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.
OG001	Part 1: BIIB033 750 mg

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.

Posted

Number

percentage of participants

Part 1: Baseline to Week 72

ID	Title	Description
OG000	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.
OG001	Part 1: BIIB033 750 mg

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)

Posted

Number

percentage of participants

Part 1: Baseline to Week 72

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Part 2: Overall Response Score

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.

Posted

Part 2: Baseline to Week 96

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

Units	Counts
Participants

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

Posted

Part 2: Baseline to Week 108

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

Units	Counts
Participants

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

Posted

Part 2: Baseline to Week 108

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

Units	Counts
Participants

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

Posted

Part 2: Baseline to Week 96

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

Units	Counts

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

Posted

Part 2: Baseline to Week 108

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

Units	Counts
Participants

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)

Posted

Part 2: Baseline to Week 108

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

Units	Counts
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

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.

Posted

Count of Participants

Participants

Part 2: Baseline to Week 96

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.

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'.

Posted

Count of Participants

Participants

Part 2: Baseline to Week 96

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

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).

Safety population included all participants who received at least 1 dose of study treatment. Participants were analyzed based on the actual treatment allocation.

Posted

Number

percentage of participants

Part 2: Baseline to Week 96

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

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.

Posted

Number

percentage of participants

Part 2: Baseline, Week 12, 24, 36, 48, 72 and 96

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

Units	Counts
Participants

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.

Posted

Count of Participants

Participants

Part 2: Baseline to Week 96

ID	Title	Description
OG000	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.
OG001	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	131	6	131	91	131
EG001	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.	1	132	9	132	93	132
EG002	Part 2: Placebo to BIIB033 750 mg	Participants who received placebo and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 80 weeks.	0	100	9	100	34	100
EG003	Part 2: BIIB033 750 mg	Participants who received BIIB033 and completed Part 1 were enrolled into Part 2 to receive BIIB033 750 mg IV as an add-on therapy to a background DMT once every 4 weeks for up to a maximum of 77 weeks.	0	113	2	113	46	113

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Congenital anomaly	Congenital, familial and genetic disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG0030 affected113 at risk
Coeliac artery compression syndrome	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG003
Chest pain	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG003
Pelvic abscess	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected131 at risk EG0010 affected132 at risk EG0020 affected100 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0021 affected100 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG003
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected131 at risk EG0010 affected132 at risk EG0020 affected100 at risk EG003
Rectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 affected131 at risk EG0010 affected132 at risk EG0020 affected100 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected131 at risk EG0010 affected132 at risk EG0020 affected100 at risk EG003
Uhthoff's phenomenon	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected131 at risk EG0010 affected132 at risk EG0020 affected100 at risk EG003
Alcohol use disorder	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected131 at risk EG0010 affected132 at risk EG0020 affected100 at risk EG003
Adenomyosis	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG003
Endometriosis	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0011 affected132 at risk EG0020 affected100 at risk EG003
Appendicitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Escherichia urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Systemic infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Chronic lymphocytic leukaemia stage 1	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Parathyroid tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0020 affected100 at risk EG003
Meningocele acquired	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0021 affected100 at risk EG003
Major depression	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected131 at risk EG0010 affected132 at risk EG0020 affected100 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00011 affected131 at risk EG0016 affected132 at risk EG0023 affected100 at risk EG0036 affected113 at risk
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00010 affected131 at risk EG00111 affected132 at risk EG0020 affected100 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0007 affected131 at risk EG0014 affected132 at risk EG0020 affected100 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG00014 affected131 at risk EG00114 affected132 at risk EG0020 affected100 at risk EG003
Bronchitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0006 affected131 at risk EG00110 affected132 at risk EG0020 affected100 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00030 affected131 at risk EG00126 affected132 at risk EG0024 affected100 at risk EG003
Sinusitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0005 affected131 at risk EG0019 affected132 at risk EG0020 affected100 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00020 affected131 at risk EG00131 affected132 at risk EG0025 affected100 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00019 affected131 at risk EG00118 affected132 at risk EG0026 affected100 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG00012 affected131 at risk EG00117 affected132 at risk EG0024 affected100 at risk EG003
Weight increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0003 affected131 at risk EG0018 affected132 at risk EG0020 affected100 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG00010 affected131 at risk EG0018 affected132 at risk EG0020 affected100 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0008 affected131 at risk EG0018 affected132 at risk EG0020 affected100 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0007 affected131 at risk EG0012 affected132 at risk EG0025 affected100 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0007 affected131 at risk EG00110 affected132 at risk EG0020 affected100 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0009 affected131 at risk EG0015 affected132 at risk EG0020 affected100 at risk EG003
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG00023 affected131 at risk EG00119 affected132 at risk EG00211 affected100 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG00020 affected131 at risk EG00123 affected132 at risk EG00212 affected100 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0008 affected131 at risk EG0017 affected132 at risk EG0020 affected100 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0008 affected131 at risk EG0019 affected132 at risk EG0020 affected100 at risk EG003

ID	Term
D020278	Demyelinating Autoimmune Diseases, CNS
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups