Clinical trial NCT00906399: Efficacy and Safety Study of Peginterferon Beta-1a in Participants With Relapsing Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing Multiple Sclerosis
Keywords: interferon
injectable
MS
SC
PEGylated
Interferon beta-1a
relapsing
PEG
multiple sclerosis
subcutaneous
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2009-05-21
Enrollment: 1516
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Annualized Relapse Rate (ARR) at 1 Year
timeFrame: 1 Year
Secondary outcomes:
measure: Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year
timeFrame: 1 Year
measure: Proportion of Participants Relapsed at 1 Year
timeFrame: Year 1
measure: Estimated Proportion of Participants With Sustained Disability Progression at 1 Year
timeFrame: 1 Year
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Ponte Vedra Beach
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Teaneck
country: United States
facility: Research Site
state: New Jersey
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Franklin
country: United States
facility: Research Site
state: Tennessee
city: Round Rock
country: United States
facility: Research Site
state: Texas
city: 'Sint-Truiden
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: London
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Santiago
country: Chile
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
state: Atlantico
city: Bogota
country: Colombia
facility: Research Site
state: Cundinamarca
city: Bogota
country: Colombia
facility: Research Site
city: Osijek
country: Croatia
facility: Research Site
city: Zagreb
country: Croatia
facility: Research Site
city: Brno
country: Czech Republic
facility: Research Site
city: Olomouc
country: Czech Republic
facility: Research Site
city: Ostrava - Vitkovice
country: Czech Republic
facility: Research Site
city: Ostrava-Poruba
country: Czech Republic
facility: Research Site
city: Ostrava
country: Czech Republic
facility: Research Site
city: Praha 2
country: Czech Republic
facility: Research Site
city: Praha 5
country: Czech Republic
facility: Research Site
city: Teplice
country: Czech Republic
facility: Research Site
city: Parnu
country: Estonia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Amiens
country: France
facility: Research Site
city: Clermont-Ferrand
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Bayreuth
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Erbach
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Koln
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Munchen
country: Germany
facility: Research Site
city: Munster
country: Germany
facility: Research Site
city: Prien
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Westerstede
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: Saket
country: India
facility: Research Site
state: Delhi
city: Ahmedabad
country: India
facility: Research Site
state: Gujarat
city: Rajkot
country: India
facility: Research Site
state: Gujarat
city: Bangalore
country: India
facility: Research Site
state: Karnataka
city: Indore
country: India
facility: Research Site
state: Madhyr Pradesh
city: Mumbai
country: India
facility: Research Site
state: Maharashtra
city: Nagpur
country: India
facility: Research Site
state: Maharashtra
city: Nasik
country: India
facility: Research Site
state: Maharashtra
city: Pune
country: India
facility: Research Site
state: Maharashtra
city: Pune
country: India
facility: Research Site
state: Maharashtra
city: Amritsar
country: India
facility: Research Site
state: Punjab
city: Jaipur
country: India
facility: Research Site
state: Rajasthan
city: Chennai
country: India
facility: Research Site
state: Tamil Nadu
city: Coimbatore
country: India
facility: Research Site
state: Tamil Nadu
city: Kolkata
country: India
facility: Research Site
state: West Bengal
city: Bangalore
country: India
facility: Research Site
city: Mangalore
country: India
facility: Research Site
city: Navi Mumbai
country: India
facility: Research Site
city: Nehru Nagar
country: India
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Aquas Calientes
country: Mexico
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Mexico DF
country: Mexico
facility: Research Site
city: Monterrey, Nuevo Leon
country: Mexico
facility: Research Site
city: Tijuana, Baja California
country: Mexico
facility: Research Site
city: Breda
country: Netherlands
facility: Research Site
city: Nieuwegein
country: Netherlands
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Dunedin
country: New Zealand
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: San Isidro
country: Peru
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Konskie
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Plewiska
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warsawa
country: Poland
facility: Research Site
city: Warsawa
country: Poland
facility: Research Site
city: Warsawa
country: Poland
facility: Research Site
city: Warsawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Zabrze
country: Poland
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Campulung
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Sibiu
country: Romania
facility: Research Site
city: Targu Mures
country: Romania
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Kaluga
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research Site
city: Kursk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Smolensk
country: Russian Federation
facility: Research Site
city: Tomsk
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Chernivtsi
country: Ukraine
facility: Research Site
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Poltava
country: Ukraine
facility: Research Site
city: Simferopol
country: Ukraine
facility: Research Site
city: Ternopil
country: Ukraine
facility: Research Site
city: Vinnytsya
country: Ukraine
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Calabresi 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.
citation: Cleanthous 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.
citation: Scott 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.
citation: Newsome 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.
citation: Arnold 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.