Efficacy and Safety Study of Peginterferon Beta-1a in Participants With Relapsing Multiple Sclerosis

Study Overview
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Brief Summary
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The primary objective of this study is to determine the efficacy of peginterferon beta-1a in reducing the annualized relapse rate (ARR) in participants with relapsing multiple sclerosis (RMS) at 1 year. The secondary objectives of this study are to determine whether peginterferon beta-1a, at 1 year when compared with placebo, is effective in reducing the total number of new or newly enlarging T2 hyperintense lesions on brain magnetic resonance imaging (MRI) scans, reducing the proportion of participants who relapse, and slowing the progression of disability.

Detailed Description
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This is a global multicenter, randomized, double-blind, parallel-group, placebo-controlled study. The treatment period is 96 weeks (2 years) in duration. Treatment Year 1 (Week 0 to Week 48) is referred to as the placebo-controlled treatment period of the study. At the beginning of Treatment Year 1, participants were randomized to receive placebo, peginterferon beta-1a 125 μg every 2 weeks, or peginterferon beta-1a 125 μg every 4 weeks. At the end of Treatment Year 1, participants in the placebo group were re-randomized to receive peginterferon beta-1a treatment so that during treatment Year 2 (Weeks 48 to Week 96) all participants received peginterferon beta-1a 125 μg every 2 or every 4 weeks. Per protocol, all primary and secondary endpoints pertain to Year 1 data.

Official Title
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A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of PEGylated Interferon Beta-1a (BIIB017) in Subjects With Relapsing Multiple Sclerosis

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: BIIB017 (peginterferon beta-1a)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have a confirmed diagnosis of relapsing multiple sclerosis (RMS), as defined by McDonald criteria 1 through 4 (Polman, 2005) Must have an EDSS score between 0.0 and 5.0. Must have experienced at least 2 relapses that have been medically documented within the last 3 years with at least one occurring in the last 12 months Key Exclusion Criteria: Other chronic disease of immune system, malignancies, urologic, pulmonary, gastrointestinal disease Pregnant or nursing women Prior treatment with interferon could not exceed 4 weeks and subjects must have discontinued interferon treatment 6 months prior to Baseline NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo every 2 weeks for 48 weeks followed by 125 µg peginterferon beta-1a subcutaneously every 2 or 4 weeks for 48 weeks. | Drug: BIIB017 (peginterferon beta-1a)<br>* Supplied as a liquid in pre-filled syringes to deliver 0.5 mL of 0.25 mg/mL (125 µg dose), self-administered by subcutaneous injection.<br>* Other names: Plegridy;Drug: Placebo<br>* Matched placebo provided in pre-filled syringes, to deliver 0.5 mL self-administered by subcutaneous injection.<br>|
| Experimental: Peginterferon Beta-1a Q2W<br>125 µg peginterferon beta-1a subcutaneously every 2 weeks (Q2W) for 96 weeks. | Drug: BIIB017 (peginterferon beta-1a)<br>* Supplied as a liquid in pre-filled syringes to deliver 0.5 mL of 0.25 mg/mL (125 µg dose), self-administered by subcutaneous injection.<br>* Other names: Plegridy;|
| Experimental: Peginterferon Beta-1a Q4W<br>125 µg peginterferon beta-1a subcutaneously every 4 weeks (Q4W) for 96 weeks. Participants received a placebo injection 2 weeks after each active injection (in order to maintain the blind with Q2W arm). | Drug: BIIB017 (peginterferon beta-1a)<br>* Supplied as a liquid in pre-filled syringes to deliver 0.5 mL of 0.25 mg/mL (125 µg dose), self-administered by subcutaneous injection.<br>* Other names: Plegridy;Drug: Placebo<br>* Matched placebo provided in pre-filled syringes, to deliver 0.5 mL self-administered by subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Relapse Rate (ARR) at 1 Year | A relapse is defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings. Only relapses confirmed by an independent neurology evaluation committee (INEC) are included in the analysis. Data after participants switched to alternative multiple sclerosis (MS) medications are excluded. Data were analyzed using negative binomial regression, adjusted for baseline Expanded Disability Status Scale (EDSS) score (< 4 versus ≥ 4), baseline age (< 40 versus ≥ 40 years), and baseline relapse rate (number of relapses in 3 years prior to study entry divided by 3). | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year | Number of new or newly enlarging T2 hyperintense lesions on brain magnetic resonance imaging (MRI) scans. Data observed after participants switched to alternative MS medications are excluded. Adjusted mean is based on negative binomial regression, adjusted for baseline number of T2 lesions. | 1 Year | 
| Proportion of Participants Relapsed at 1 Year | A relapse is defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings. Only relapses confirmed by INEC were included in the analysis. Estimated proportion of participants relapsed is based on the Kaplan-Meier product limit method. | Year 1 | 
| Estimated Proportion of Participants With Sustained Disability Progression at 1 Year | Sustained disability progression is defined as: at least a 1.0 point increase on the EDSS from baseline EDSS ≥ 1.0 that is sustained for 12 weeks, or at least a 1.5 point increase on the EDSS from baseline EDSS = 0 that is sustained for 12 weeks. The EDSS measures the disability status of people with MS on a scale that ranges from 0 to 10. The range of main categories include 0 (normal neurologic examination), to 5 (ambulatory without aid or rest for 200 meters/disability severe enough to impair full daily activities), to 10 (death due to MS). Estimated proportion of participants with progression based on the Kaplan-Meier product limit method. | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interferon, injectable, MS, SC, PEGylated, Interferon beta-1a, relapsing, PEG, multiple sclerosis, subcutaneous