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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00906399
First received: May 20, 2009
Last updated: September 15, 2014
Last verified: September 2014

May 20, 2009
September 15, 2014
June 2009
October 2012   (final data collection date for primary outcome measure)
Annualized Relapse Rate (ARR) at 1 Year [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
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).
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 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00906399 on ClinicalTrials.gov Archive Site
  • Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy and Safety Study of Peginterferon Beta-1a in Participants With Relapsing Multiple Sclerosis
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Relapsing Multiple Sclerosis
  • 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.
  • 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
Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ, Boyko A, Pelletier J, Liu S, Zhu Y, Seddighzadeh A, Hung S, Deykin A; ADVANCE Study Investigators. Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014 Jul;13(7):657-65. doi: 10.1016/S1474-4422(14)70068-7. Epub 2014 Apr 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1516
October 2013
October 2012   (final data collection date for primary outcome measure)

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.

Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   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
 
NCT00906399
105MS301, 2008-006333-27
Yes
Biogen Idec
Biogen Idec
Not Provided
Study Director: Medical Director Biogen Idec
Biogen Idec
September 2014

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