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
Results First Received: July 23, 2009  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Intervention: Drug: Interferon beta-1b (Betaseron, BAY86-5046)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The full analysis set includes all 468 participants (particip.) with at least one administration of study drug in the placebo-controlled original study 92012, using treatment groups as randomized according to the minimization procedure regardless of the kind of study treatment (IFNB-1b/placebo) received. 19 subjects did not consent to the Follow-up

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

Participant Flow for 2 periods

Period 1:   Placebo-controlled Study (92012)
    Initial IFNB-1b (Interferon Beta-1b)     Initial Placebo  
STARTED     292     176  
COMPLETED     271     166  
NOT COMPLETED     21     10  
Adverse Event                 8                 0  
Lost to Follow-up                 3                 2  
Withdrawal by Subject                 9                 7  
fulfilled local def. and McDonald crit.                 0                 1  
Adverse event, then subject's withdrawal                 1                 0  

Period 2:   Follow-up Study (91031 - This Study)
    Initial IFNB-1b (Interferon Beta-1b)     Initial Placebo  
STARTED     261 [1]   157 [2]
COMPLETED     235     123  
NOT COMPLETED     26     34  
Adverse Event                 5                 6  
Lack of Efficacy                 1                 0  
Lost to Follow-up                 6                 4  
Physician Decision                 1                 0  
Pregnancy                 0                 1  
Withdrawal by Subject                 13                 21  
other disease modif. treatment                 0                 2  
[1] 10 of the 271 subjects completing the placebo-controlled study did not consent to the Follow-up.
[2] 9 of the 166 subjects completing the placebo-controlled study did not consent to the Follow-up.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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
Initial Placebo Initial placebo treatment; Betaferon/Betaseron, 250 ug administered s.c. (subcutaneous) every other day offered in Follow-up phase (= this trial)
Total Total of all reporting groups

Baseline Measures
    Initial IFNB-1b (Interferon Beta-1b)     Initial Placebo     Total  
Number of Participants  
[units: participants]
  292     176     468  
Age  
[units: years]
Mean ± Standard Deviation
  30.8  ± 7.6     30.7  ± 7.1     30.7  ± 7.4  
Gender  
[units: participants]
     
Female     207     124     331  
Male     85     52     137  
Number of T2 lesions detected in screening MRI (Magnet-Resonance Imaging) [1]
[units: participants]
     
2 to 4 T2 lesions     42     25     67  
5 to 8 T2 lesions     43     28     71  
at least 9 T2 lesions     207     123     330  
Number of participants with steroid use during the first clinical demyelinating event [2]
[units: participants]
     
Steroid Use     209     123     332  
No Steroid Use     83     53     136  
Type of onset of disease (classification of first demyelinating event) [3]
[units: participants]
     
monofocal disease     153     93     246  
multifocal disease     139     83     222  
[1] Only patients with at least two clinically silent lesions on the T2-weighted brain MRI scan with a size of at least 3 mm, at least one of which is ovoid or periventricular or infratentorial, were included. Number of T2 lesions with the three categories was used in the minimization procedure.
[2] The allocation of participants to the treatment arms was according to a minimization procedure with an element of randomization to minimize imbalances of treatment groups with respect to e.g. steroid use during first clinical demyelinating event. Steroid treatment was at the discretion of the investigator.
[3] On the basis of the central classification of the patient’s symptoms and signs, the first event was classified as either monofocal (a single central nervous system (CNS) lesion suffices to explain the patient’s symptoms and signs) or multifocal (the patient’s symptoms and signs can only be explained by multiple (i.e. more than one) CNS lesions.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Month 60   [ Time Frame: 60 months after start of treatment ]

4.  Secondary:   Relapse-based Efficacy Domain: Time to Multiple Sclerosis (MS) According to McDonald Criteria   [ Time Frame: up to 60 months after start of treatment ]

5.  Secondary:   Relapse-based Efficacy Domain: Hazard Ratio for Recurrent Relapses   [ Time Frame: up to 60 months after start of treatment ]

6.  Secondary:   Relapse-based Efficacy Domain (Supportive): Annualized Relapse Rate   [ Time Frame: up to 60 months after start of treatment ]

7.  Secondary:   Disability-based Efficacy Domain: Multiple Sclerosis Functional Composite (MSFC) at Month 60   [ Time Frame: 60 months after start of treatment ]

8.  Secondary:   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 ]

9.  Secondary:   MRI-based Efficacy Domain: Absolute Change of T2 Lesion Volume From Screening MRI to Month 60   [ Time Frame: 60 months after start of treatment ]

10.  Secondary:   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 ]

11.  Secondary:   MRI-based Efficacy Domain: Percentage Change of Brain Volume From Screening MRI to Month 60   [ Time Frame: 60 months after start of treatment ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Other 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