Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis (TEMSO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00134563
First received: August 23, 2005
Last updated: January 2, 2013
Last verified: January 2013
Results First Received: October 3, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Teriflunomide
Drug: Placebo (for teriflunomide)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

The recruitment initiated in September 2004 was completed in February 2008.

A total of 1338 patients were screened at 127 sites in 21 countries.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Randomization was stratified by country and baseline disability (Expanded Disability Status Scale [EDSS] score ≤3.5 or >3.5).

Assignment to groups was done centrally using an Interactive Voice Response System (IVRS] in a 1:1:1 ratio after confirmation of the selection criteria.

1088 participants were randomized.


Reporting Groups
  Description
Placebo Placebo (for teriflunomide) once daily for 108 weeks
Teriflunomide 7 mg Teriflunomide 7 mg once daily for 108 weeks
Teriflunomide 14 mg Teriflunomide 14 mg once daily for 108 weeks

Participant Flow:   Overall Study
    Placebo     Teriflunomide 7 mg     Teriflunomide 14 mg  
STARTED     363 [1]   366 [1]   359 [1]
Treated     363 [2]   365     358 [3]
COMPLETED     259 [4]   274 [4]   263 [4]
NOT COMPLETED     104     92     96  
Not treated due to protocol violation                 0                 1                 1  
Adverse Event                 29                 37                 38  
Lack of Efficacy                 24                 14                 17  
Protocol Violation                 3                 2                 5  
Lost to Follow-up                 4                 0                 2  
progressive disease                 11                 4                 2  
did not wish to continue                 33                 32                 26  
Reason other than above                 0                 2                 5  
[1] Randomized
[2] Two participants received doses of Teriflunomide 7 mg, one participant doses of Teriflunomide 14 mg
[3] one participant received doses of Teriflunomide 7 mg
[4] completed treatment period



  Baseline Characteristics
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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
Placebo Placebo (for teriflunomide) once daily for 108 weeks
Teriflunomide 7 mg Teriflunomide 7 mg once daily for 108 weeks
Teriflunomide 14 mg Teriflunomide 14 mg once daily for 108 weeks
Total Total of all reporting groups

Baseline Measures
    Placebo     Teriflunomide 7 mg     Teriflunomide 14 mg     Total  
Number of Participants  
[units: participants]
  363     365     358     1086  
Age [1]
[units: years]
Mean ± Standard Deviation
  38.4  ± 9.0     37.5  ± 9.0     37.8  ± 8.2     37.9  ± 8.8  
Gender  
[units: participants]
       
Female     275     254     254     783  
Male     88     111     104     303  
Region of enrollment [2]
[units: participants]
       
America     82     83     80     245  
Eastern Europe     114     116     108     338  
Western Europe     167     166     170     503  
Time since first diagnosis of multiple sclerosis (MS) [3]
[units: Years]
Mean ± Standard Deviation
  5.13  ± 5.59     5.29  ± 5.36     5.59  ± 5.44     5.33  ± 5.48  
Number of MS relapses  
[units: MSĀ relapses]
Median ( Full Range )
       
Within the past year     1  
  ( 0 to 6 )  
  1  
  ( 0 to 6 )  
  1  
  ( 0 to 4 )  
  1  
  ( 0 to 6 )  
Within the past 2 years     2  
  ( 1 to 7 )  
  2  
  ( 1 to 12 )  
  2  
  ( 1 to 9 )  
  2  
  ( 1 to 12 )  
Time since most recent MS relapse onset  
[units: months]
Mean ± Standard Deviation
  6.28  ± 3.62     6.29  ± 3.29     6.50  ± 3.71     6.35  ± 3.54  
MS subtype  
[units: participants]
       
Relapsing Remitting     329     332     332     993  
Secondary Progressive     22     17     12     51  
Progressive Relapsing     12     16     14     42  
MS medication in the past 2 years  
[units: participants]
       
Yes     90     102     102     294  
No     273     263     256     792  
Baseline EDSS total score [4]
[units: participants]
       
≤ 3.5     281     280     276     837  
> 3.5     82     85     82     249  
[1] Baseline characteristics of the population included in analyses
[2]

America: Canada, Chile, and United States;

Eastern Europe: Czech Republic, Estonia, Poland, Russia and Ukraine;

Western Europe: Austria, Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Portugal, Sweden, Switzerland, Turkey, and United Kingdom;

[3] The information was missing for one participant in the Teriflunomide 7 mg group.
[4]

EDSS is an ordinal scale in half-point increments that qualifies disability in patients with MS. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation.

EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS).




  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Annualized Relapse Rate [ARR]: Poisson Regression Estimates   [ Time Frame: 108 weeks ]

2.  Secondary:   Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints   [ Time Frame: 108 weeks ]

3.  Secondary:   Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)   [ Time Frame: baseline (before randomization) and 108 weeks ]

4.  Secondary:   Changes From Baseline in Fatigue Impact Scale [FIS] Total Score   [ Time Frame: baseline (before randomization) and 108 weeks ]

5.  Other Pre-specified:   Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)   [ Time Frame: 108 weeks ]

6.  Other Pre-specified:   Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan   [ Time Frame: 108 weeks ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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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.


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
No text entered.  


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
e-mail: Contact_US@sanofi-aventis.com


Publications of Results:
Publications automatically indexed to this study:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00134563     History of Changes
Other Study ID Numbers: EFC6049, 2004-000555-42, HMR1726D/3001
Study First Received: August 23, 2005
Results First Received: October 3, 2012
Last Updated: January 2, 2013
Health Authority: Canada: Health Canada
France: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
United States: Food and Drug Administration