Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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
  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

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
  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
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 
Overall Participants Analyzed 
[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) 
[1] Baseline characteristics of the population included in analyses
Gender 
[Units: Participants]
       
Female   275   254   254   783 
Male   88   111   104   303 
Region of enrollment [1] 
[Units: Participants]
       
America   82   83   80   245 
Eastern Europe   114   116   108   338 
Western Europe   167   166   170   503 
[1]

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;

Time since first diagnosis of multiple sclerosis (MS) [1] 
[Units: Years]
Mean (Standard Deviation)
 5.13  (5.59)   5.29  (5.36)   5.59  (5.44)   5.33  (5.48) 
[1] The information was missing for one participant in the Teriflunomide 7 mg group.
Number of MS relapses 
[Units: MS 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 [1] 
[Units: Participants]
       
≤ 3.5   281   280   276   837 
> 3.5   82   85   82   249 
[1]

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


  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
No text entered.


  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: Trial Transparency Team
Organization: sanofi-aventis
e-mail: Contact_US@sanofi-aventis.com


Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00134563     History of Changes
Other Study ID Numbers: EFC6049
2004-000555-42 ( EudraCT Number )
HMR1726D/3001 ( Other Identifier: HMR )
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