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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00185211

  Show 94 Study Locations
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
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Interferon beta-1b
Interferon-beta
Interferons
Adjuvants, Immunologic
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014