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

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:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Interferon Interferon beta Interferon beta-1a Avonex Peginterferon beta-1a

U.S. FDA Resources

Further study details as provided by Biogen:

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 (Adult)
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

Show 178 Study Locations

Sponsors and Collaborators

Biogen

Investigators


Study Director:	Medical Director	Biogen

More Information

Publications:

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 β-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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Newsome SD, Guo S, Altincatal A, Proskorovsky I, Kinter E, Phillips G, You X, Sabatella G. Impact of peginterferon beta-1a and disease factors on quality of life in multiple sclerosis. Mult Scler Relat Disord. 2015 Jul;4(4):350-7. doi: 10.1016/j.msard.2015.06.004. Epub 2015 Jun 14.

Arnold DL, Calabresi PA, Kieseier BC, Sheikh SI, Deykin A, Zhu Y, Liu S, You X, Sperling B, Hung S. Effect of peginterferon beta-1a on MRI measures and achieving no evidence of disease activity: results from a randomized controlled trial in relapsing-remitting multiple sclerosis. BMC Neurol. 2014 Dec 31;14:240. doi: 10.1186/s12883-014-0240-x.

Kieseier BC, Arnold DL, Balcer LJ, Boyko AA, Pelletier J, Liu S, Zhu Y, Seddighzadeh A, Hung S, Deykin A, Sheikh SI, Calabresi PA. Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE. Mult Scler. 2015 Jul;21(8):1025-35. doi: 10.1177/1352458514557986. Epub 2014 Nov 28.

Hu X, Cui Y, White J, Zhu Y, Deykin A, Nestorov I, Hung S. Pharmacokinetics and pharmacodynamics of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis in the randomized ADVANCE study. Br J Clin Pharmacol. 2015 Mar;79(3):514-22. doi: 10.1111/bcp.12521.


Responsible Party:	Biogen
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:


interferon injectable MS SC PEGylated	Interferon beta-1a relapsing PEG multiple sclerosis subcutaneous

Additional relevant MeSH terms:


Sclerosis Multiple Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases	Interferons Interferon-beta Interferon beta-1a Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunologic Factors Physiological Effects of Drugs Adjuvants, Immunologic

ClinicalTrials.gov processed this record on September 29, 2016

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