Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00906399




Registration number
NCT00906399
Ethics application status
Date submitted
20/05/2009
Date registered
21/05/2009
Date last updated
19/09/2014

Titles & IDs
Public title
Efficacy and Safety Study of Peginterferon Beta-1a in Participants With Relapsing Multiple Sclerosis
Scientific 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
Secondary ID [1] 0 0
2008-006333-27
Secondary ID [2] 0 0
105MS301
Universal Trial Number (UTN)
Trial acronym
ADVANCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BIIB017 (peginterferon beta-1a)
Treatment: Drugs - Placebo

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.

Experimental: Peginterferon Beta-1a Q2W - 125 µg peginterferon beta-1a subcutaneously every 2 weeks (Q2W) for 96 weeks.

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).


Treatment: Drugs: 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.

Treatment: Drugs: Placebo
Matched placebo provided in pre-filled syringes, to deliver 0.5 mL self-administered by subcutaneous injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Relapse Rate (ARR) at 1 Year
Timepoint [1] 0 0
1 Year
Secondary outcome [1] 0 0
Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year
Timepoint [1] 0 0
1 Year
Secondary outcome [2] 0 0
Proportion of Participants Relapsed at 1 Year
Timepoint [2] 0 0
Year 1
Secondary outcome [3] 0 0
Estimated Proportion of Participants With Sustained Disability Progression at 1 Year
Timepoint [3] 0 0
1 Year

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2013
Sample size
Target
Accrual to date
Final
1516
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Belgium
State/province [12] 0 0
'Sint-Truiden
Country [13] 0 0
Belgium
State/province [13] 0 0
Bruxelles
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Plovdiv
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Chile
State/province [18] 0 0
Santiago
Country [19] 0 0
Colombia
State/province [19] 0 0
Atlantico
Country [20] 0 0
Colombia
State/province [20] 0 0
Cundinamarca
Country [21] 0 0
Colombia
State/province [21] 0 0
Bogota
Country [22] 0 0
Croatia
State/province [22] 0 0
Osijek
Country [23] 0 0
Croatia
State/province [23] 0 0
Zagreb
Country [24] 0 0
Czech Republic
State/province [24] 0 0
Brno
Country [25] 0 0
Czech Republic
State/province [25] 0 0
Olomouc
Country [26] 0 0
Czech Republic
State/province [26] 0 0
Ostrava - Vitkovice
Country [27] 0 0
Czech Republic
State/province [27] 0 0
Ostrava-Poruba
Country [28] 0 0
Czech Republic
State/province [28] 0 0
Ostrava
Country [29] 0 0
Czech Republic
State/province [29] 0 0
Praha 2
Country [30] 0 0
Czech Republic
State/province [30] 0 0
Praha 5
Country [31] 0 0
Czech Republic
State/province [31] 0 0
Teplice
Country [32] 0 0
Estonia
State/province [32] 0 0
Parnu
Country [33] 0 0
Estonia
State/province [33] 0 0
Tallinn
Country [34] 0 0
Estonia
State/province [34] 0 0
Tartu
Country [35] 0 0
France
State/province [35] 0 0
Amiens
Country [36] 0 0
France
State/province [36] 0 0
Clermont-Ferrand
Country [37] 0 0
France
State/province [37] 0 0
Lyon
Country [38] 0 0
France
State/province [38] 0 0
Marseille
Country [39] 0 0
France
State/province [39] 0 0
Nice
Country [40] 0 0
Georgia
State/province [40] 0 0
Tbilisi
Country [41] 0 0
Germany
State/province [41] 0 0
Bayreuth
Country [42] 0 0
Germany
State/province [42] 0 0
Berlin
Country [43] 0 0
Germany
State/province [43] 0 0
Bochum
Country [44] 0 0
Germany
State/province [44] 0 0
Erbach
Country [45] 0 0
Germany
State/province [45] 0 0
Erlangen
Country [46] 0 0
Germany
State/province [46] 0 0
Hamburg
Country [47] 0 0
Germany
State/province [47] 0 0
Hannover
Country [48] 0 0
Germany
State/province [48] 0 0
Koln
Country [49] 0 0
Germany
State/province [49] 0 0
Leipzig
Country [50] 0 0
Germany
State/province [50] 0 0
Marburg
Country [51] 0 0
Germany
State/province [51] 0 0
Munchen
Country [52] 0 0
Germany
State/province [52] 0 0
Munster
Country [53] 0 0
Germany
State/province [53] 0 0
Prien
Country [54] 0 0
Germany
State/province [54] 0 0
Ulm
Country [55] 0 0
Germany
State/province [55] 0 0
Westerstede
Country [56] 0 0
Greece
State/province [56] 0 0
Athens
Country [57] 0 0
Greece
State/province [57] 0 0
Thessaloniki
Country [58] 0 0
India
State/province [58] 0 0
Delhi
Country [59] 0 0
India
State/province [59] 0 0
Gujarat
Country [60] 0 0
India
State/province [60] 0 0
Karnataka
Country [61] 0 0
India
State/province [61] 0 0
Madhyr Pradesh
Country [62] 0 0
India
State/province [62] 0 0
Maharashtra
Country [63] 0 0
India
State/province [63] 0 0
Punjab
Country [64] 0 0
India
State/province [64] 0 0
Rajasthan
Country [65] 0 0
India
State/province [65] 0 0
Tamil Nadu
Country [66] 0 0
India
State/province [66] 0 0
West Bengal
Country [67] 0 0
India
State/province [67] 0 0
Bangalore
Country [68] 0 0
India
State/province [68] 0 0
Mangalore
Country [69] 0 0
India
State/province [69] 0 0
Navi Mumbai
Country [70] 0 0
India
State/province [70] 0 0
Nehru Nagar
Country [71] 0 0
Latvia
State/province [71] 0 0
Riga
Country [72] 0 0
Mexico
State/province [72] 0 0
Aquas Calientes
Country [73] 0 0
Mexico
State/province [73] 0 0
Chihuahua
Country [74] 0 0
Mexico
State/province [74] 0 0
Mexico City
Country [75] 0 0
Mexico
State/province [75] 0 0
Mexico DF
Country [76] 0 0
Mexico
State/province [76] 0 0
Monterrey, Nuevo Leon
Country [77] 0 0
Mexico
State/province [77] 0 0
Tijuana, Baja California
Country [78] 0 0
Netherlands
State/province [78] 0 0
Breda
Country [79] 0 0
Netherlands
State/province [79] 0 0
Nieuwegein
Country [80] 0 0
New Zealand
State/province [80] 0 0
Auckland
Country [81] 0 0
New Zealand
State/province [81] 0 0
Christchurch
Country [82] 0 0
New Zealand
State/province [82] 0 0
Dunedin
Country [83] 0 0
Peru
State/province [83] 0 0
Lima
Country [84] 0 0
Peru
State/province [84] 0 0
San Isidro
Country [85] 0 0
Poland
State/province [85] 0 0
Bialystok
Country [86] 0 0
Poland
State/province [86] 0 0
Bydgoszcz
Country [87] 0 0
Poland
State/province [87] 0 0
Gdansk
Country [88] 0 0
Poland
State/province [88] 0 0
Katowice
Country [89] 0 0
Poland
State/province [89] 0 0
Konskie
Country [90] 0 0
Poland
State/province [90] 0 0
Krakow
Country [91] 0 0
Poland
State/province [91] 0 0
Lodz
Country [92] 0 0
Poland
State/province [92] 0 0
Lublin
Country [93] 0 0
Poland
State/province [93] 0 0
Olsztyn
Country [94] 0 0
Poland
State/province [94] 0 0
Plewiska
Country [95] 0 0
Poland
State/province [95] 0 0
Poznan
Country [96] 0 0
Poland
State/province [96] 0 0
Szczecin
Country [97] 0 0
Poland
State/province [97] 0 0
Warsawa
Country [98] 0 0
Poland
State/province [98] 0 0
Wroclaw
Country [99] 0 0
Poland
State/province [99] 0 0
Zabrze
Country [100] 0 0
Romania
State/province [100] 0 0
Brasov
Country [101] 0 0
Romania
State/province [101] 0 0
Bucharest
Country [102] 0 0
Romania
State/province [102] 0 0
Campulung
Country [103] 0 0
Romania
State/province [103] 0 0
Iasi
Country [104] 0 0
Romania
State/province [104] 0 0
Sibiu
Country [105] 0 0
Romania
State/province [105] 0 0
Targu Mures
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Chelyabinsk
Country [107] 0 0
Russian Federation
State/province [107] 0 0
Kaluga
Country [108] 0 0
Russian Federation
State/province [108] 0 0
Kazan
Country [109] 0 0
Russian Federation
State/province [109] 0 0
Krasnodar
Country [110] 0 0
Russian Federation
State/province [110] 0 0
Kursk
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Moscow
Country [112] 0 0
Russian Federation
State/province [112] 0 0
Novosibirsk
Country [113] 0 0
Russian Federation
State/province [113] 0 0
Perm
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Rostov-on-Don
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Smolensk
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Tomsk
Country [117] 0 0
Russian Federation
State/province [117] 0 0
Ufa
Country [118] 0 0
Serbia
State/province [118] 0 0
Belgrade
Country [119] 0 0
Serbia
State/province [119] 0 0
Kragujevac
Country [120] 0 0
Serbia
State/province [120] 0 0
Nis
Country [121] 0 0
Spain
State/province [121] 0 0
Cordoba
Country [122] 0 0
Spain
State/province [122] 0 0
Madrid
Country [123] 0 0
Spain
State/province [123] 0 0
Malaga
Country [124] 0 0
Spain
State/province [124] 0 0
Sevilla
Country [125] 0 0
Ukraine
State/province [125] 0 0
Chernivtsi
Country [126] 0 0
Ukraine
State/province [126] 0 0
Dnipropetrovsk
Country [127] 0 0
Ukraine
State/province [127] 0 0
Donetsk
Country [128] 0 0
Ukraine
State/province [128] 0 0
Kharkiv
Country [129] 0 0
Ukraine
State/province [129] 0 0
Kyiv
Country [130] 0 0
Ukraine
State/province [130] 0 0
Odesa
Country [131] 0 0
Ukraine
State/province [131] 0 0
Poltava
Country [132] 0 0
Ukraine
State/province [132] 0 0
Simferopol
Country [133] 0 0
Ukraine
State/province [133] 0 0
Ternopil
Country [134] 0 0
Ukraine
State/province [134] 0 0
Vinnytsya
Country [135] 0 0
United Kingdom
State/province [135] 0 0
London
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Nottingham
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Salford
Country [138] 0 0
United Kingdom
State/province [138] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT00906399
Trial related presentations / 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 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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00906399