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

Phase 3

Completed

Conditions: Relapsing Multiple Sclerosis

Interventions: Drug: BIIB017 (peginterferon beta-1a)
Drug: Placebo

Registration Number: NCT00906399

Lead Sponsor: Biogen

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1516

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	BIIB017 (peginterferon beta-1a)	Placebo every 2 weeks for 48 weeks followed by 125 µg peginterferon beta-1a subcutaneously every 2 or 4 weeks for 48 weeks.
Peginterferon Beta-1a Q2W	BIIB017 (peginterferon beta-1a)	125 µg peginterferon beta-1a subcutaneously every 2 weeks (Q2W) for 96 weeks.
Peginterferon Beta-1a Q4W	Placebo	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).
Placebo	Placebo	Placebo every 2 weeks for 48 weeks followed by 125 µg peginterferon beta-1a subcutaneously every 2 or 4 weeks for 48 weeks.
Peginterferon Beta-1a Q4W	BIIB017 (peginterferon beta-1a)	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).

Primary Outcome Measures

Name	Time	Method
Annualized Relapse Rate (ARR) at 1 Year	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).

Secondary Outcome Measures

Name	Time	Method
Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year	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.
Proportion of Participants Relapsed at 1 Year	Year 1	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.
Estimated Proportion of Participants With Sustained Disability Progression at 1 Year	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.