Clinical trial NCT00185211: BENEFIT Study (Betaferon® / Betaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment) and BENEFIT Follow-up Study
Official title: Open-label, Multi-center Phase III Extension of the Double-blind, Placebo-controlled BENEFIT Study (no. 92012/304747) to Obtain Long-term Follow-up Data of Patients With Clinically Definite Multiple Sclerosis (MS) and Patients With a First Demyelinating Event Suggestive of MS Treated With 8 MIU (250 µg) Interferon Beta-1b (Betaferon® / Betaseron®) Given Subcutaneously Every Other Day for at Least 36 Months.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2005-09-16
Enrollment: 468
Sex: ALL
Minimum age (years): 18
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will primarily compare the long-term effects of an early and continued treatment with Betaferon/Betaseron (patients who were treated with active medication during the double-blind BENEFIT study) to treatment initiated either after Clinically Definite Multiple Sclerosis (CDMS) has been diagnosed or after two years (those patients who were treated with placebo during the double-blind BENEFIT study).

Analyses are based on the integrated data of the initial BENEFIT study and this follow-up study.

Detailed description: The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer HealthCare Pharmaceuticals Inc..

Bayer HealthCare Pharmaceuticals Inc. is the sponsor of the trial.

Eligibility criteria: Inclusion Criteria:

* Patients who have reached scheduled end of study in BENEFIT, either by developing CDMS or by completing 24 months

Exclusion Criteria:

* No participation in the initial BENEFIT study

Primary outcomes:
measure: Time to Clinically Definite Multiple Sclerosis (CDMS) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS at Selected Points in Time
timeFrame: up to 60 months after start of treatment
measure: Time to Confirmed Expanded Disability Status Scale (EDSS) Progression Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With Confirmed EDSS Progression at Selected Points in Time
timeFrame: up to 60 months after start of treatment
measure: Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Month 60
timeFrame: 60 months after start of treatment
Secondary outcomes:
measure: Relapse-based Efficacy Domain: Time to Multiple Sclerosis (MS) According to McDonald Criteria
timeFrame: up to 60 months after start of treatment
measure: Relapse-based Efficacy Domain: Hazard Ratio for Recurrent Relapses
timeFrame: up to 60 months after start of treatment
measure: Relapse-based Efficacy Domain (Supportive): Annualized Relapse Rate
timeFrame: up to 60 months after start of treatment
measure: Disability-based Efficacy Domain: Multiple Sclerosis Functional Composite (MSFC) at Month 60
timeFrame: 60 months after start of treatment
measure: MRI (Magnet-Resonance Imaging)-Based Efficacy Domain: Cumulative Number of Newly Active Lesions at Month 60
timeFrame: up to 60 months after start of treatment
measure: MRI-based Efficacy Domain: Absolute Change of T2 Lesion Volume From Screening MRI to Month 60
timeFrame: 60 months after start of treatment
measure: MRI-based Efficacy Domain: Absolute Change of Volume of Black Holes From Screening MRI to Month 60
timeFrame: 60 months after start of treatment
measure: MRI-based Efficacy Domain: Percentage Change of Brain Volume From Screening MRI to Month 60
timeFrame: 60 months after start of treatment
Other outcomes:
Locations:
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Wien
country: Austria
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liège 1
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Brno
country: Czech Republic
city: Hradec Kralove
country: Czech Republic
city: Ostrava
country: Czech Republic
city: Plzen
country: Czech Republic
city: Prag
country: Czech Republic
city: Prag
country: Czech Republic
city: Glostrup
country: Denmark
city: Helsinki
country: Finland
city: Kuopio
country: Finland
city: Oulu
country: Finland
city: Seinäjoki
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Rennes
country: France
state: Bretagne
city: Bordeaux
country: France
state: Gironde
city: Clermont ferrand
country: France
city: Dijon
country: France
city: Lille
country: France
city: Nancy
country: France
city: Nice
country: France
city: Paris
country: France
city: Toulouse
country: France
city: Ulm
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Regensburg
country: Germany
state: Bayern
city: Würzburg
country: Germany
state: Bayern
city: Hennigsdorf
country: Germany
state: Brandenburg
city: Gießen
country: Germany
state: Hessen
city: Marburg
country: Germany
state: Hessen
city: Offenbach
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Braunschweig
country: Germany
state: Niedersachsen
city: Göttingen
country: Germany
state: Niedersachsen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Münster
country: Germany
state: Nordrhein-Westfalen
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Homburg
country: Germany
state: Saarland
city: Halle
country: Germany
state: Sachsen-Anhalt
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Erfurt
country: Germany
state: Thüringen
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Szeged
country: Hungary
state: Csongrad
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Haifa
country: Israel
city: Tel Hashomer
country: Israel
city: Gallarate
country: Italy
state: Varese
city: Milano
country: Italy
city: Padova
country: Italy
city: Pavia
country: Italy
city: Torino
country: Italy
city: Sittard
country: Netherlands
city: Tilburg
country: Netherlands
city: Bergen
country: Norway
city: Bydgoszcz
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Wroclaw
country: Poland
city: Coimbra
country: Portugal
city: Lubljana
country: Slovenia
city: Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Barakaldo
country: Spain
state: Vizcaya
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Basel
country: Switzerland
state: Basel-Stadt
city: St. Gallen
country: Switzerland
city: Dundee
country: United Kingdom
state: Scotland
city: Aberdeen
country: United Kingdom
city: London
country: United Kingdom
city: Sheffield
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Edan G, Kappos L, Montalban X, Polman CH, Freedman MS, Hartung HP, Miller D, Barkhof F, Herrmann J, Lanius V, Stemper B, Pohl C, Sandbrink R, Pleimes D; BENEFIT Study Group. Long-term impact of interferon beta-1b in patients with CIS: 8-year follow-up of BENEFIT. J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1183-9. doi: 10.1136/jnnp-2013-306222. Epub 2013 Nov 11.
citation: Nagtegaal GJ, Pohl C, Wattjes MP, Hulst HE, Freedman MS, Hartung HP, Miller D, Montalban X, Kappos L, Edan G, Pleimes D, Beckman K, Stemper B, Polman CH, Sandbrink R, Barkhof F. Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome. Mult Scler. 2014 Feb;20(2):234-42. doi: 10.1177/1352458513494491. Epub 2013 Jul 10.
citation: Penner IK, Stemper B, Calabrese P, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Pleimes D, Lanius V, Pohl C, Kappos L, Sandbrink R. Effects of interferon beta-1b on cognitive performance in patients with a first event suggestive of multiple sclerosis. Mult Scler. 2012 Oct;18(10):1466-71. doi: 10.1177/1352458512442438. Epub 2012 Apr 4.
citation: Kappos L, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Radu EW, Metzig C, Bauer L, Lanius V, Sandbrink R, Pohl C; BENEFIT Study Group. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol. 2009 Nov;8(11):987-97. doi: 10.1016/S1474-4422(09)70237-6. Epub 2009 Sep 10.
citation: Hartung HP, Freedman MS, Polman CH, Edan G, Kappos L, Miller DH, Montalban X, Barkhof F, Petkau J, White R, Sahajpal V, Knappertz V, Beckmann K, Lanius V, Sandbrink R, Pohl C; BENEFIT Study Group. Interferon beta-1b-neutralizing antibodies 5 years after clinically isolated syndrome. Neurology. 2011 Aug 30;77(9):835-43. doi: 10.1212/WNL.0b013e31822c90d7. Epub 2011 Aug 17.
citation: Freedman MS, Metzig C, Kappos L, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Yarden J, Spector L, Fire E, Dotan N, Schwenke S, Lanius V, Sandbrink R, Pohl C. Predictive nature of IgM anti-alpha-glucose serum biomarker for relapse activity and EDSS progression in CIS patients: a BENEFIT study analysis. Mult Scler. 2012 Jul;18(7):966-73. doi: 10.1177/1352458511432327. Epub 2011 Dec 19.
citation: Waschbisch A, Sandbrink R, Hartung HP, Kappos L, Schwab S, Pohl C, Wiendl H. Evaluation of soluble HLA-G as a biomarker for multiple sclerosis. Neurology. 2011 Aug 9;77(6):596-8. doi: 10.1212/WNL.0b013e318228c14d. Epub 2011 Jul 27. No abstract available.
citation: Moraal B, Pohl C, Uitdehaag BM, Polman CH, Edan G, Freedman MS, Hartung HP, Kappos L, Miller DH, Montalban X, Lanius V, Sandbrink R, Barkhof F. Magnetic resonance imaging predictors of conversion to multiple sclerosis in the BENEFIT study. Arch Neurol. 2009 Nov;66(11):1345-52. doi: 10.1001/archneurol.2009.243.
citation: Polman C, Kappos L, Freedman MS, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Selmaj K, Uitdehaag BM, Dahms S, Bauer L, Pohl C, Sandbrink R; BENEFIT investigators. Subgroups of the BENEFIT study: risk of developing MS and treatment effect of interferon beta-1b. J Neurol. 2008 Apr;255(4):480-7. doi: 10.1007/s00415-007-0733-2. Epub 2007 Nov 15.
citation: Caloyeras JP, Zhang B, Wang C, Eriksson M, Fredrikson S, Beckmann K, Knappertz V, Pohl C, Hartung HP, Shah D, Miller JD, Sandbrink R, Lanius V, Gondek K, Russell MW. Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis. Clin Ther. 2012 May;34(5):1132-44. doi: 10.1016/j.clinthera.2012.03.004. Epub 2012 Apr 27.
citation: Nielsen JM, Pohl C, Polman CH, Barkhof F, Freedman MS, Edan G, Miller DH, Bauer L, Sandbrink R, Kappos L, Uitdehaag BM. MRI characteristics are predictive for CDMS in monofocal, but not in multifocal patients with a clinically isolated syndrome. BMC Neurol. 2009 May 20;9:19. doi: 10.1186/1471-2377-9-19.
citation: Barkhof F, Polman CH, Radue EW, Kappos L, Freedman MS, Edan G, Hartung HP, Miller DH, Montalban X, Poppe P, de Vos M, Lasri F, Bauer L, Dahms S, Wagner K, Pohl C, Sandbrink R. Magnetic resonance imaging effects of interferon beta-1b in the BENEFIT study: integrated 2-year results. Arch Neurol. 2007 Sep;64(9):1292-8. doi: 10.1001/archneur.64.9.1292.
citation: Kappos L, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Radu EW, Bauer L, Dahms S, Lanius V, Pohl C, Sandbrink R; BENEFIT Study Group. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet. 2007 Aug 4;370(9585):389-97. doi: 10.1016/S0140-6736(07)61194-5.
citation: De Jager PL, Chibnik LB, Cui J, Reischl J, Lehr S, Simon KC, Aubin C, Bauer D, Heubach JF, Sandbrink R, Tyblova M, Lelkova P; Steering committee of the BENEFIT study; Steering committee of the BEYOND study; Steering committee of the LTF study; Steering committee of the CCR1 study; Havrdova E, Pohl C, Horakova D, Ascherio A, Hafler DA, Karlson EW. Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score. Lancet Neurol. 2009 Dec;8(12):1111-9. doi: 10.1016/S1474-4422(09)70275-3. Epub 2009 Oct 29.