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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00185211
First received: September 9, 2005
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: Interferon beta-1b (Betaseron, BAY86-5046)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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 [ Time Frame: up to 60 months after start of treatment ] [ Designated as safety issue: No ]
    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)

  • 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 [ Time Frame: up to 60 months after start of treatment ] [ Designated as safety issue: No ]
    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.

  • Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Month 60 [ Time Frame: 60 months after start of treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Relapse-based Efficacy Domain: Time to Multiple Sclerosis (MS) According to McDonald Criteria [ Time Frame: up to 60 months after start of treatment ] [ Designated as safety issue: No ]
    MS according to the criteria by McDonald was reached if, in addition to the single clinical demyelinating event, both dissemination in space and dissemination in time were established by MRI-criteria or a new relapse. Time to McDonald MS is the difference of date of McDonald MS to the date of Day 1 + 1. For subjects without McDonald MS, time to McDonald MS is the difference from the maximum (date of last magnetic resonance imaging scan, date of last clinical visit) to the date of Day 1 + 1 (right-censored observation).

  • Relapse-based Efficacy Domain: Hazard Ratio for Recurrent Relapses [ Time Frame: up to 60 months after start of treatment ] [ Designated as safety issue: No ]
    A relapse was defined as the appearance of a new neurological abnormality or the reappearance of a neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The time to the onset of recurrent relapses was determined for each subject according to the counting process representation for recurrent events. Time to a relapse was right-censored if a relapse-risk period ended without relapse. Based on the Andersen-Gill model the hazard ratio for recurrent relapses was estimated. Annualized relapse rates are provided as another outcome measure.

  • Relapse-based Efficacy Domain (Supportive): Annualized Relapse Rate [ Time Frame: up to 60 months after start of treatment ] [ Designated as safety issue: No ]
    The annualized relapse rate is defined as total number of relapses up to month 60 divided by the total observation time (last clinical visit minus first day of study treatment administration plus 1 of all participants) in years.

  • Disability-based Efficacy Domain: Multiple Sclerosis Functional Composite (MSFC) at Month 60 [ Time Frame: 60 months after start of treatment ] [ Designated as safety issue: No ]
    The MSFC score consists of three sub-tests (Timed-25-Foot-Walk, 9-Hole-Peg-Test, 3" Paced Auditory Serial Addition Test [PASAT]). Standardized results (Z-scores) of the sub-tests and the overall MSFC Z-score as an average of the three Z-scores were derived using baseline data pooled over both treatment arms as reference population. Higher Z-scores reflect a better neurological status.

  • MRI (Magnet-Resonance Imaging)-Based Efficacy Domain: Cumulative Number of Newly Active Lesions at Month 60 [ Time Frame: up to 60 months after start of treatment ] [ Designated as safety issue: No ]
    Newly active lesions are defined as displaying either new Gadolinium (Gd)-enhancement on T1-weighted scans or non-enhancement on T1-weighted scan but new on T2-weighted scan. The numbers of newly active lesions on yearly MRI scans were summed up to the cumulative number.

  • MRI-based Efficacy Domain: Absolute Change of T2 Lesion Volume From Screening MRI to Month 60 [ Time Frame: 60 months after start of treatment ] [ Designated as safety issue: No ]
    Absolute change of T2 lesion volume from screening MRI to month 60 was calculated as T2 lesion volume at month 60 minus T2 lesion volume at screening.

  • MRI-based Efficacy Domain: Absolute Change of Volume of Black Holes From Screening MRI to Month 60 [ Time Frame: 60 months after start of treatment ] [ Designated as safety issue: No ]
    Absolute change of volume of black holes from screening MRI to month 60 was calculated as volume of black holes at month 60 minus volume of black holes at screening.

  • MRI-based Efficacy Domain: Percentage Change of Brain Volume From Screening MRI to Month 60 [ Time Frame: 60 months after start of treatment ] [ Designated as safety issue: No ]
    Two-timepoint percentage brain volume change was estimated with Structural Image Evaluation, using Normalisation, of Atrophy (SIENA) software. The measurements describe the percentage change from screening in brain volume at month 60.


Enrollment: 468
Study Start Date: August 2002
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Initial IFNB-1b (Interferon beta-1b)
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 Betaferon/Betaseron treatment (Interferon beta-1b, IFNB-1b), 250 ug administered s.c. (subcutaneous) every other day, continued in Follow-up phase
Experimental: Initial Placebo
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)
Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)

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

Ages Eligible for Study:   18 Years to 48 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00185211

  Hide Study Locations
Locations
Austria
Graz, Austria, 8036
Innsbruck, Austria, 6020
Wien, Austria, 1090
Belgium
Bruxelles, Belgium, 1200
Gent, Belgium, 9000
Leuven, Belgium, 3000
Liège 1, Belgium, 4000
Canada, Alberta
Calgary, Alberta, Canada, T2N 2T9
Canada, British Columbia
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Ontario
London, Ontario, Canada, N6A 5A5
Ottawa, Ontario, Canada, K1H 8L6
Toronto, Ontario, Canada, M5B 1W8
Canada, Quebec
Montreal, Quebec, Canada, H2L 4M1
Czech Republic
Brno, Czech Republic, 63900
Hradec Kralove, Czech Republic, 50005
Ostrava, Czech Republic, 70852
Plzen, Czech Republic, 30460
Prag, Czech Republic, 10034
Prag, Czech Republic, 12808
Denmark
Glostrup, Denmark, 2600
Finland
Helsinki, Finland, 00100
Kuopio, Finland, 70210
Oulu, Finland, 90029
Seinäjoki, Finland, 60220
Tampere, Finland, 33521
Turku, Finland, 20100
France
Rennes, Bretagne, France, 35038
Bordeaux, Gironde, France, 33076
Clermont ferrand, France, 63003
Dijon, France, 21033
Lille, France, 59037
Nancy, France, 54035
Nice, France, 06000
Paris, France, 75019
Toulouse, France, 31059
Germany
Ulm, Baden-Württemberg, Germany, 89081
München, Bayern, Germany, 81377
Regensburg, Bayern, Germany, 93053
Würzburg, Bayern, Germany, 97080
Hennigsdorf, Brandenburg, Germany, 16761
Gießen, Hessen, Germany, 35392
Marburg, Hessen, Germany, 35039
Offenbach, Hessen, Germany, 63069
Greifswald, Mecklenburg-Vorpommern, Germany, 17475
Braunschweig, Niedersachsen, Germany, 38126
Göttingen, Niedersachsen, Germany, 37099
Düsseldorf, Nordrhein-Westfalen, Germany, 40479
Düsseldorf, Nordrhein-Westfalen, Germany, 40225
Köln, Nordrhein-Westfalen, Germany, 50931
Münster, Nordrhein-Westfalen, Germany, 48149
Mainz, Rheinland-Pfalz, Germany, 55101
Homburg, Saarland, Germany, 66424
Halle, Sachsen-Anhalt, Germany, 06120
Magdeburg, Sachsen-Anhalt, Germany, 39120
Erfurt, Thüringen, Germany, 99089
Berlin, Germany, 13585
Berlin, Germany, 12200
Hungary
Szeged, Csongrad, Hungary, 6720
Budapest, Hungary, 1145
Budapest, Hungary, 1204
Budapest, Hungary, 1076
Debrecen, Hungary, 4032
Israel
Haifa, Israel, 34362
Tel Hashomer, Israel, 52621
Italy
Gallarate, Varese, Italy, 21013
Milano, Italy, 20132
Padova, Italy, 35128
Pavia, Italy, 27100
Torino, Italy, 10126
Netherlands
Sittard, Netherlands, 6131 BK
Tilburg, Netherlands, 5022 GC
Norway
Bergen, Norway, N-5021
Poland
Bydgoszcz, Poland, 85681
Krakow, Poland, 31503
Lodz, Poland, 90153
Lublin, Poland, 20090
Wroclaw, Poland, 50420
Portugal
Coimbra, Portugal, 3000
Slovenia
Lubljana, Slovenia, 1525
Spain
Hospitalet de Llobregat, Barcelona, Spain, 08907
Barakaldo, Vizcaya, Spain, 48903
Barcelona, Spain, 08036
Barcelona, Spain, 08035
Madrid, Spain, 28040
Malaga, Spain, 29010
Sevilla, Spain, 41071
Valencia, Spain, 46026
Sweden
Göteborg, Sweden, 41685
Switzerland
Basel, Basel-Stadt, Switzerland, 4031
St. Gallen, Switzerland, 9007
United Kingdom
Dundee, Scotland, United Kingdom, DD1 9SY
Aberdeen, United Kingdom, AB25 2ZN
London, United Kingdom, W6 8RF
Sheffield, United Kingdom, S10 2JF
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00185211     History of Changes
Other Study ID Numbers: 91031, 305207
Study First Received: September 9, 2005
Results First Received: July 23, 2009
Last Updated: December 4, 2013
Health Authority: United States: Food and Drug Administration
Austria: Federal Ministry for Health and Women
Canada: Health Canada
Netherlands: Dutch Health Care Inspectorate
Switzerland: Swissmedic
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Denmark: Danish Medicines Agency
Spain: Ministry of Health and Consumption
France: French Data Protection Authority
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Finland: Finnish Medicines Agency
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Norway: Norwegian Medicines Agency
Portugal: National Pharmacy and Medicines Institute
Poland: Ministry of Health
Sweden: Medical Products Agency
Slovenia: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferons
Interferon beta-1b
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on April 17, 2014