Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Participants With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the efficacy of BIIB033 in participants with active relapsing multiple sclerosis (MS) when used concurrently with Avonex. Secondary objectives of this study in this study population are to assess the safety, tolerability, and population pharmacokinetics of BIIB033 when used concurrently with Avonex.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: BIIB033
* Other: Placebo
* Drug: Avonex


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of relapsing remitting MS (RRMS) or onset of secondary progressive MS (SPMS) RRMS and SPMS subjects must have evidence of ongoing disease activity within 12 months of enrollment. All male and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after their last dose of study treatment Key Exclusion Criteria: A MS relapse that has occurred within the 90 days prior to Day 1/Baseline and/or the subject has not stabilized from a previous relapse prior to Screening Previous history of clinically significant disease. Plans to undergo elective major procedures/surgeries at any time during the study. Treatment with any investigational MS drugs within 3 weeks or 5 times the half life (whichever is longer) prior to Day 1/Baseline RRMS subjects with any history of inadequate response to any approved interferon β preparation History of human immunodeficiency virus (HIV), hepatitis C virus antibody, or hepatitis B virus History or evidence of drug or alcohol abuse within 2 years prior to randomization Note: Other protocol defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 58 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIIB033, 3 mg/kg<br>BIIB033 3 mg/kg once every 4 weeks intravenous (IV) infusion up to Week 72. Avonex once-weekly intramuscular (IM) injection up to Week 84. | Drug: BIIB033<br> <br> * Other names: anti-LINGO-1 mAb;Drug: Avonex<br> <br> * Other names: interferon beta-1a;|
| Experimental: BIIB033, 10 mg/kg<br>BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84. | Drug: BIIB033<br> <br> * Other names: anti-LINGO-1 mAb;Drug: Avonex<br> <br> * Other names: interferon beta-1a;|
| Experimental: BIIB033, 30 mg/kg<br>BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84. | Drug: BIIB033<br> <br> * Other names: anti-LINGO-1 mAb;Drug: Avonex<br> <br> * Other names: interferon beta-1a;|
| Experimental: BIIB033, 100 mg/kg<br>BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84. | Drug: BIIB033<br> <br> * Other names: anti-LINGO-1 mAb;Drug: Avonex<br> <br> * Other names: interferon beta-1a;|
| Placebo Comparator: Placebo<br>Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84. | Other: Placebo<br> <br> Drug: Avonex<br> <br> * Other names: interferon beta-1a;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint | Estimated proportion of participants experiencing confirmed improvement in any 1 or more of the following components: a ≥1 point decrease in the Expanded Disability Status Scale (EDSS) score from a baseline score of <=6.0 (decrease sustained for ≥3 months); a ≥15% improvement from baseline in time to complete 9-Hole Peg Test (9HPT) by either hand (improvement sustained for ≥3 months for the same hand), where the time is the average time of 2 trials per hand at the same visit; a ≥15% improvement from baseline in time to complete Timed 25-Foot Walk (T25FW) test (improvement sustained for ≥3 months), where the time is the average time of 2 trials at the same visit; or a ≥15% improvement from baseline 3-Second Paced Auditory Serial Addition Test (PASAT-3) score (improvement sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for multiple sclerosis (MS) type, region and baseline component assessments. | 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint | Estimated proportion of participants experiencing confirmed clinical worsening in 1 or more components of the multicomponent endpoint (EDSS, T25FW, 9HPT, or PASAT-3) over 72 weeks, defined as: a ≥1.0 point increase in EDSS from a baseline score of ≤5.5 or a ≥0.5 point increase from a baseline score equal to 6.0 (increase sustained for 3 months or greater); a ≥15%worsening from baseline in time to complete T25FW test (worsening sustained for 3 months or greater), where the time is the average of 2 trials at the same visit; a ≥15% worsening from baseline in time to complete 9HPT by either hand (worsening sustained for 3 months or greater for the same hand), where the time is the average of 2 trials for each hand at the same visit; a ≥15% worsening from baseline in PASAT-3 score (worsening sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for MS type, region and baseline component assessments. | 72 weeks | 
| Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs | An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the participant at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. | Up to 84 weeks | 
| Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 |  | Up to 84 weeks |