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

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ClinicalTrials.gov Identifier: NCT00906399
Recruitment Status : Completed
First Posted : May 21, 2009
Results First Posted : September 19, 2014
Last Update Posted : September 19, 2014
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE May 20, 2009
First Posted Date  ICMJE May 21, 2009
Results First Submitted Date  ICMJE July 28, 2014
Results First Posted Date  ICMJE September 19, 2014
Last Update Posted Date September 19, 2014
Study Start Date  ICMJE June 2009
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 15, 2014)
Annualized Relapse Rate (ARR) at 1 Year [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: May 20, 2009)
To determine the efficacy of BIIB017 in reducing the Annualized Relapse Rate (ARR) in subjects with RMS at 1 year compared to placebo. [ Time Frame: 1 Year ]
Change History Complete list of historical versions of study NCT00906399 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2014)
  • Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2009)
To determine whether BIIB017, at 1 year when compared with placebo, is effective in reducing the total number new brain lesions, reducing the proportion of subjects who relapsed, improving quality of life, and slowing the progression of disability. [ Time Frame: 1 year +2 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of Peginterferon Beta-1a in Participants With Relapsing Multiple Sclerosis
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Relapsing Multiple Sclerosis
Intervention  ICMJE
  • Drug: BIIB017 (peginterferon beta-1a)
    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.
    Other Names:
    • PEG IFN ß-1a
    • PEGylated interferon beta-1a
    • Plegridy
  • Drug: Placebo
    Matched placebo provided in pre-filled syringes, to deliver 0.5 mL self-administered by subcutaneous injection.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo every 2 weeks for 48 weeks followed by 125 µg peginterferon beta-1a subcutaneously every 2 or 4 weeks for 48 weeks.
    Interventions:
    • Drug: BIIB017 (peginterferon beta-1a)
    • Drug: Placebo
  • Experimental: Peginterferon Beta-1a Q2W
    125 µg peginterferon beta-1a subcutaneously every 2 weeks (Q2W) for 96 weeks.
    Intervention: Drug: BIIB017 (peginterferon beta-1a)
  • Experimental: Peginterferon Beta-1a Q4W
    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).
    Interventions:
    • Drug: BIIB017 (peginterferon beta-1a)
    • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 16, 2012)
1516
Original Estimated Enrollment  ICMJE
 (submitted: May 20, 2009)
1260
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Bulgaria,   Canada,   Chile,   Colombia,   Croatia,   Czech Republic,   Estonia,   France,   Georgia,   Germany,   Greece,   India,   Latvia,   Mexico,   Netherlands,   New Zealand,   Peru,   Poland,   Romania,   Russian Federation,   Serbia,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00906399
Other Study ID Numbers  ICMJE 105MS301
2008-006333-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP