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
  Purpose

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.


Condition Intervention Phase
Relapsing Multiple Sclerosis
Drug: BIIB017 (peginterferon beta-1a)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 1516
Study Start Date: June 2009
Study Completion Date: October 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Experimental: Peginterferon Beta-1a Q2W
125 µg peginterferon beta-1a subcutaneously every 2 weeks (Q2W) for 96 weeks.
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
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).
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00906399

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Sponsors and Collaborators
Biogen Idec
Investigators
Study Director: Medical Director Biogen Idec
  More Information

Publications:
Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT00906399     History of Changes
Other Study ID Numbers: 105MS301, 2008-006333-27
Study First Received: May 20, 2009
Results First Received: July 28, 2014
Last Updated: September 15, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Romania: Ministry of Public Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Serbia: Ethics Committee
Mexico: Federal Commission for Protection Against Health Risks
Ukraine: State Expert Centre of the Ministry of Health of Ukraine
Greece: Ministry of Health and Welfare
Greece: Ethics Committee
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Estonia: The State Agency of Medicine
New Zealand: Medsafe
Czech Republic: State Institute for Drug Control
Peru: Instituto Nacional de Salud
Poland: Ministry of Health
Russia: Ethics Committee
Netherlands: Independent Ethics Committee
Czech Republic: Ethics Committee
Peru: Ethics Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Croatia: Ministry of Health and Social Care
Georgia: Ministry of Health
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Latvia: State Agency of Medicines
United States: Food and Drug Administration
Chile: Instituto de Salud Pública de Chile
India: Central Drugs Standard Control Organization
Romania: Ethics Committee
Russia: Ministry of Health of the Russian Federation

Keywords provided by Biogen Idec:
interferon
injectable
MS
SC
PEGylated
Interferon beta-1a
relapsing
PEG
multiple sclerosis
subcutaneous

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Interferon beta 1a
Interferon-beta
Interferons
Adjuvants, Immunologic
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014