BENEFIT Study (Betaferon® / Betaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment) and BENEFIT Follow-up Study

NCT00185211 | Completed Phase 3 Results DMC

• 2 other identifiers: 91031305207
• Study Type: interventional
• Target: 468
• Locations: 20 countries
• Sites: 94

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (3)

• 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

  CDMS could be reached due to a qualifying relapse or sustained progression of 1.5 points on the expanded disability status scale (EDSS) as compared to the lowest EDSS obtained during screening or Day 1. The validity of CDMS diagnoses was confirmed by a central committee. The EDSS scale quantifies disability in MS in 8 functional systems, values vary between 0="normal neurological examination" and 10="death due to MS" measured in half-points on an ordinal scale. Time to CDMS = date of CDMS - date of Day 1 + 1 or time to CDMS = date of last clinical visit - date of Day 1 + 1 (right-censored)

  up to 60 months after start of treatment

• 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

  EDSS progression was defined as an increase in the expanded disability status scale (EDSS) of 1.0 point compared to the lowest EDSS score obtained during the screening or baseline visit, if this score was \<= 5.5. A confirmed EDSS progression status was defined as an EDSS progression observed at two consecutive scheduled visits at least 140 days apart from each other. The EDSS scale is a method of quantifying disability in multiple sclerosis in eight functional systems and values vary between 0="normal neurological examination" and 10="death due to MS" measured in half-points on a scale.

  up to 60 months after start of treatment

• Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Month 60

  As an index of health related quality of life in people diagnosed with MS, the FAMS Trial Outcome Index covers overall physical health (sum of sub-scale scores Mobility, Symptoms, Thinking/Fatigue, Additional Concerns) with a score range from 0 to 148. A higher score reflects a higher overall physical health as reported by patients.

  60 months after start of treatment

Secondary Outcomes (8)

• Relapse-based Efficacy Domain: Time to Multiple Sclerosis (MS) According to McDonald Criteria

  up to 60 months after start of treatment

• Relapse-based Efficacy Domain: Hazard Ratio for Recurrent Relapses

  up to 60 months after start of treatment

• Relapse-based Efficacy Domain (Supportive): Annualized Relapse Rate

  up to 60 months after start of treatment

• Disability-based Efficacy Domain: Multiple Sclerosis Functional Composite (MSFC) at Month 60

  60 months after start of treatment

• MRI (Magnet-Resonance Imaging)-Based Efficacy Domain: Cumulative Number of Newly Active Lesions at Month 60

  up to 60 months after start of treatment

Study Arms (2)

Initial IFNB-1b (Interferon beta-1b)

EXPERIMENTAL

Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase

Drug: Interferon beta-1b (Betaseron, BAY86-5046)

Initial Placebo

EXPERIMENTAL

Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)

Drug: Interferon beta-1b (Betaseron, BAY86-5046)

Interventions

Interferon beta-1b (Betaseron, BAY86-5046) DRUG

Initial Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase

Initial IFNB-1b (Interferon beta-1b)

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• No participation in the initial BENEFIT study

Sponsors & Collaborators

• Bayer: lead

Study Sites (94)

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Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Vienna, 1090, Austria

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Calgary, Alberta, T2N 2T9, Canada

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Vancouver, British Columbia, V6T 2B5, Canada

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London, Ontario, N6A 5A5, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Brno, 63900, Czechia

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Hradec Králové, 50005, Czechia

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Ostrava, 70852, Czechia

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Pilsen, 30460, Czechia

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Prague, 10034, Czechia

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Prague, 12808, Czechia

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Glostrup Municipality, 2600, Denmark

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Helsinki, 00100, Finland

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Kuopio, 70210, Finland

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Oulu, 90029, Finland

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Seinäjoki, 60220, Finland

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Tampere, 33521, Finland

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Turku, 20100, Finland

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Rennes, Brittany Region, 35038, France

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Bordeaux, Gironde, 33076, France

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Clermont-Ferrand, 63003, France

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Dijon, 21033, France

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Lille, 59037, France

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Nancy, 54035, France

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Nice, 06000, France

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Paris, 75019, France

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Toulouse, 31059, France

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Ulm, Baden-Wurttemberg, 89081, Germany

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München, Bavaria, 81377, Germany

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Regensburg, Bavaria, 93053, Germany

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Würzburg, Bavaria, 97080, Germany

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Hennigsdorf, Brandenburg, 16761, Germany

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Giessen, Hesse, 35392, Germany

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Marburg, Hesse, 35039, Germany

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Offenbach, Hesse, 63069, Germany

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Braunschweig, Lower Saxony, 38126, Germany

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Göttingen, Lower Saxony, 37099, Germany

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Greifswald, Mecklenburg-Vorpommern, 17475, Germany

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Cologne, North Rhine-Westphalia, 50931, Germany

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Düsseldorf, North Rhine-Westphalia, 40225, Germany

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Düsseldorf, North Rhine-Westphalia, 40479, Germany

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Münster, North Rhine-Westphalia, 48149, Germany

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Mainz, Rhineland-Palatinate, 55101, Germany

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Homburg, Saarland, 66424, Germany

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Halle, Saxony-Anhalt, 06120, Germany

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Magdeburg, Saxony-Anhalt, 39120, Germany

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Berlin, State of Berlin, 12200, Germany

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Berlin, State of Berlin, 13585, Germany

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Erfurt, Thuringia, 99089, Germany

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Szeged, Csongrád megye, 6720, Hungary

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Budapest, 1076, Hungary

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Budapest, 1145, Hungary

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Budapest, 1204, Hungary

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Debrecen, 4032, Hungary

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Haifa, Israel, 34362, Israel

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Tel Litwinsky, Israel, 52621, Israel

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Gallarate, Varese, 21013, Italy

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Milan, 20132, Italy

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Padua, 35128, Italy

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Pavia, 27100, Italy

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Torino, 10126, Italy

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Sittard, 6131 BK, Netherlands

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Tilburg, 5022 GC, Netherlands

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Bergen, N-5021, Norway

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Bydgoszcz, 85681, Poland

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Krakow, 31503, Poland

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Lodz, 90153, Poland

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Lublin, 20090, Poland

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Wroclaw, 50420, Poland

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Coimbra, 3000, Portugal

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Ljubljana, 1525, Slovenia

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L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Barakaldo, Vizcaya, 48903, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Madrid, 28040, Spain

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Málaga, 29010, Spain

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Seville, 41071, Spain

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Valencia, 46026, Spain

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Gothenburg, 41685, Sweden

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Basel, Canton of Basel-City, 4031, Switzerland

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Sankt Gallen, 9007, Switzerland

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Dundee, Scotland, DD1 9SY, United Kingdom

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Aberdeen, AB25 2ZN, United Kingdom

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London, W6 8RF, United Kingdom

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Sheffield, S10 2JF, United Kingdom

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Related Publications (14)

• 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.

  PMID: 24218527 BACKGROUND

• 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.

  PMID: 23842212 BACKGROUND

• 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.

  PMID: 22492127 BACKGROUND

• 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.

  PMID: 19748319 RESULT

• 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.

  PMID: 21849647 RESULT

• 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.

  PMID: 22183938 RESULT

• 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.

  PMID: 21795647 RESULT

• 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.

  PMID: 19901165 RESULT

• 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.

  PMID: 18004635 RESULT

• 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.

  PMID: 22541587 RESULT

• 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.

  PMID: 19457248 RESULT

• 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.

  PMID: 17846268 RESULT

• 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.

  PMID: 17679016 RESULT

• 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.

  PMID: 19879194 RESULT

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Interferon beta-1b

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Participant Flow: Subject with "Other" as reason for not completing a study period are presented according to the NIH pre-specified categories as far as possible.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 16, 2005
• Study Start: August 1, 2002
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: December 30, 2013
• Results First Posted: November 30, 2010

Record last verified: 2013-12

Locations

IL (2); PL (5); HU (5); DK (1); FI (6); NO (1); AU (3); PT (1); CH (2); ES (8); CZ (6); CA (6); SL (1); FR (9); IT (5); SE (1); GB (4); NL (2); DE (22); BE (4)