Efficacy and Safety Study of Peginterferon Beta-1a in Participants With Relapsing Multiple Sclerosis
ADVANCE
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
2 other identifiers
interventional
1,516
25 countries
173
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2009
Typical duration for phase_3
173 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 20, 2009
CompletedFirst Posted
Study publicly available on registry
May 21, 2009
CompletedStudy Start
First participant enrolled
June 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2013
CompletedResults Posted
Study results publicly available
September 19, 2014
CompletedSeptember 19, 2014
September 1, 2014
3.3 years
May 20, 2009
July 28, 2014
September 15, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Annualized Relapse Rate (ARR) at 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).
1 Year
Secondary Outcomes (3)
Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year
1 Year
Proportion of Participants Relapsed at 1 Year
Year 1
Estimated Proportion of Participants With Sustained Disability Progression at 1 Year
1 Year
Study Arms (3)
Placebo
PLACEBO COMPARATORPlacebo 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
EXPERIMENTAL125 µg peginterferon beta-1a subcutaneously every 2 weeks (Q2W) for 96 weeks.
Peginterferon Beta-1a Q4W
EXPERIMENTAL125 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
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.
Matched placebo provided in pre-filled syringes, to deliver 0.5 mL self-administered by subcutaneous injection.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Biogenlead
Study Sites (178)
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Phoenix, Arizona, 85013, United States
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Ponte Vedra Beach, Florida, 32082 4040, United States
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Atlanta, Georgia, 30327, United States
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Des Moines, Iowa, 50314, United States
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Lexington, Kentucky, 40513, United States
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Baltimore, Maryland, 21287, United States
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Teaneck, New Jersey, 07666, United States
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Raleigh, North Carolina, 27607 6520, United States
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Akron, Ohio, 44320, United States
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Cleveland, Ohio, 44195, United States
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Franklin, Tennessee, 37064, United States
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Round Rock, Texas, 78681, United States
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Brussels, 1200, Belgium
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Sint-Truiden, 3800, Belgium
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Plovdiv, 4002, Bulgaria
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Sofia, 1113, Bulgaria
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Sofia, 1309, Bulgaria
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Sofia, 1407, Bulgaria
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Sofia, 1431, Bulgaria
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Sofia, 1527, Bulgaria
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Sofia, 1606, Bulgaria
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London, Ontario, N6A 5A5, Canada
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Montreal, Quebec, H2L4M1, Canada
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Santiago, 8207257, Chile
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Barranquilla, Atlántico, Colombia
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Bogota, Cundinamarca, Colombia
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Bogotá, Colombia
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Osijek, 31000, Croatia
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Zagreb, 10000, Croatia
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Brno, 62500, Czechia
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Olomouc, 77520, Czechia
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Ostrava, 70852, Czechia
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Ostrava - Vitkovice, 70200, Czechia
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Ostrava-Poruba, 70300, Czechia
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Prague, 12808, Czechia
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Prague, 15006, Czechia
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Teplice, 41529, Czechia
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Pärnu, EE 80010, Estonia
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Tallinn, EE 10617, Estonia
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Tartu, EE 51014, Estonia
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Amiens, 80054, France
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Clermont-Ferrand, 63003, France
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Lyon, 69394, France
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Marseille, 13385, France
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Nice, 6002, France
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Tbilisi, 112, Georgia
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Tbilisi, 141, Georgia
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Tbilisi, 179, Georgia
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Tbilisi, 186, Georgia
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Bayreuth, 95445, Germany
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Berlin, 10713, Germany
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Berlin, 14163, Germany
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Bochum, 44791, Germany
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Cologne, 50935, Germany
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Erbach im Odenwald, 64711, Germany
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Erlangen, 91054, Germany
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Hamburg, 20099, Germany
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Hanover, 30559, Germany
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Leipzig, 04103, Germany
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Marburg, 35043, Germany
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München, 80331, Germany
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Münster, 48149, Germany
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Prien am Chiemsee, 83209, Germany
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Ulm, 89079, Germany
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Westerstede, 26655, Germany
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Athens, 11521, Greece
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Athens, 11525, Greece
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Thessaloniki, 57010, Greece
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Ahmedabad, Gujarat, 380006, India
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Rajkot, Gujarat, 360001, India
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Bangalore, Karnataka, 560043, India
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Indore, Madhyr Pradesh, 452018, India
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Mumbai, Maharashtra, 400026, India
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Nagpur, Maharashtra, 440010, India
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Nashik, Maharashtra, 422004, India
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Pune, Maharashtra, 411004, India
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Pune, Maharashtra, 411030, India
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New Delhi, National Capital Territory of Delhi, 110029, India
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New Delhi, National Capital Territory of Delhi, 110060, India
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Saket, National Capital Territory of Delhi, 110017, India
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Amritsar, Punjab, 143001, India
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Jaipur, Rajasthan, 302004, India
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Chennai, Tamil Nadu, 600017, India
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Coimbatore, Tamil Nadu, 641014, India
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Kolkata, West Bengal, 700068, India
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Bangalore, 560017, India
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Mangalore, 575018, India
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Navi Mumbai, 400703, India
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Nehru Nagar, 110065, India
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Riga, LV 1005, Latvia
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Aquas Calientes, 20127, Mexico
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Chihuahua City, 31203, Mexico
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Mexico City, 03310, Mexico
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Mexico City, 10700, Mexico
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Monterrey, Nuevo Leon, 64710, Mexico
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Tijuana, Baja California, 22320, Mexico
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Breda, 4818CK, Netherlands
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Nieuwegein, 3435CM, Netherlands
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Auckland, 1023, New Zealand
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Christchurch, New Zealand
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Dunedin, New Zealand
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Lima, Lima 01, Peru
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Lima, Lima 1, Peru
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Lima, Lima 21, Peru
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San Isidro, Lima 27, Peru
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Bialystok, 15276, Poland
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Bialystok, 15402, Poland
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Bydgoszcz, 85681, Poland
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Gdansk, 80299, Poland
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Gdansk, 80803, Poland
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Gdansk, 80952, Poland
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Gmina Końskie, 26200, Poland
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Katowice, 40650, Poland
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Katowice, 40662, Poland
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Katowice, 40684, Poland
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Krakow, 31505, Poland
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Krakow, 31637, Poland
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Krakow, 31826, Poland
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Lodz, 90153, Poland
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Lublin, 20718, Poland
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Lublin, 20954, Poland
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Olsztyn, 10082, Poland
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Plewiska, 62064, Poland
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Poznan, 60355, Poland
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Poznan, 61853, Poland
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Szczecin, 70215, Poland
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Szczecin, 71252, Poland
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Warsaw, 00851, Poland
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Warsaw, 02957, Poland
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Warsaw, 04141, Poland
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Warsaw, 04749, Poland
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Wroclaw, 50556, Poland
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Zabrze, 41800, Poland
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Brasov, 500123, Romania
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Bucharest, 50098, Romania
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Campulung Muscel, 115100, Romania
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Iași, 700656, Romania
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Sibiu, 550166, Romania
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Târgu Mureş, 540136, Romania
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Chelyabinsk, 454136, Russia
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Kaluga, 248007, Russia
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Kazan', 420021, Russia
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Krasnodar, 350012, Russia
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Kursk, 305007, Russia
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Moscow, 107150, Russia
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Moscow, 119021, Russia
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Moscow, 125367, Russia
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Moscow, 127018, Russia
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Novosibirsk, 630007, Russia
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Perm, 614990, Russia
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Rostov-on-Don, 344015, Russia
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Smolensk, 214018, Russia
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Tomsk, 634050, Russia
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Ufa, 450005, Russia
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Belgrade, 11000, Serbia
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Kragujevac, 34000, Serbia
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Niš, 18000, Serbia
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Córdoba, 14008, Spain
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Madrid, 28041, Spain
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Madrid, 28046, Spain
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Málaga, 29010, Spain
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Seville, 41071, Spain
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Chernivtsi, 58018, Ukraine
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Dnipropetrovsk, 49027, Ukraine
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Donetsk, 83099, Ukraine
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Kharkiv, 61068, Ukraine
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Kharkiv, 61103, Ukraine
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Kyiv, 3110, Ukraine
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Kyiv, 4107, Ukraine
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Odesa, 65025, Ukraine
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Poltava, 26011, Ukraine
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Simferopol, 95017, Ukraine
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Ternopil, 46027, Ukraine
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Vinnytsia, 21005, Ukraine
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London, E1 1BB, United Kingdom
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Nottingham, NG7 2UH, United Kingdom
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Salford, M6 8HD, United Kingdom
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Sheffield, S10 2JF, United Kingdom
Related Publications (11)
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.
PMID: 24794721RESULTLoomis SJ, Sadhu N, Fisher E, Gafson AR, Huang Y, Yang C, Hughes EE, Marshall E, Herman A, John S, Runz H, Jia X, Bhangale T, Bronson PG. Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials. Sci Rep. 2023 Aug 31;13(1):14313. doi: 10.1038/s41598-023-41099-0.
PMID: 37652990DERIVEDCalabresi PA, Arnold DL, Sangurdekar D, Singh CM, Altincatal A, de Moor C, Engle B, Goyal J, Deykin A, Szak S, Kieseier BC, Rudick RA, Plavina T. Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring. Mult Scler. 2021 Sep;27(10):1497-1505. doi: 10.1177/1352458520972573. Epub 2020 Dec 14.
PMID: 33307998DERIVEDCleanthous S, Cano S, Kinter E, Marquis P, Petrillo J, You X, Wakeford C, Sabatella G. Measuring the impact of multiple sclerosis: Enhancing the measurement performance of the Multiple Sclerosis Impact Scale (MSIS-29) using Rasch Measurement Theory (RMT). Mult Scler J Exp Transl Clin. 2017 Aug 15;3(3):2055217317725917. doi: 10.1177/2055217317725917. eCollection 2017 Jul-Sep.
PMID: 29104758DERIVEDScott TF, Kieseier BC, Newsome SD, Arnold DL, You X, Hung S, Sperling B. Improvement in relapse recovery with peginterferon beta-1a in patients with multiple sclerosis. Mult Scler J Exp Transl Clin. 2016 Nov 15;2:2055217316676644. doi: 10.1177/2055217316676644. eCollection 2016 Jan-Dec.
PMID: 28607743DERIVEDNewsome SD, Kieseier BC, Liu S, You X, Kinter E, Hung S, Sperling B. Peginterferon beta-1a reduces disability worsening in relapsing-remitting multiple sclerosis: 2-year results from ADVANCE. Ther Adv Neurol Disord. 2017 Jan;10(1):41-50. doi: 10.1177/1756285616676065. Epub 2016 Nov 16.
PMID: 28450894DERIVEDArnold DL, Calabresi PA, Kieseier BC, Liu S, You X, Fiore D, Hung S. Peginterferon beta-1a improves MRI measures and increases the proportion of patients with no evidence of disease activity in relapsing-remitting multiple sclerosis: 2-year results from the ADVANCE randomized controlled trial. BMC Neurol. 2017 Feb 10;17(1):29. doi: 10.1186/s12883-017-0799-0.
PMID: 28183276DERIVEDNewsome 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.
PMID: 26195056DERIVEDArnold 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.
PMID: 25551571DERIVEDKieseier 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.
PMID: 25432952DERIVEDHu 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.
PMID: 25265472DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Biogen Idec Study Medical Director
- Organization
- Biogen Idec
Study Officials
- STUDY DIRECTOR
Medical Director
Biogen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 20, 2009
First Posted
May 21, 2009
Study Start
June 1, 2009
Primary Completion
October 1, 2012
Study Completion
October 1, 2013
Last Updated
September 19, 2014
Results First Posted
September 19, 2014
Record last verified: 2014-09