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Phase II Study of Teriflunomide as Adjunctive Therapy to Interferon-beta in Subjects With Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT00489489
Recruitment Status : Completed
First Posted : June 21, 2007
Results First Posted : November 2, 2012
Last Update Posted : November 6, 2012
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Teriflunomide
Drug: Placebo (for Teriflunomide)
Drug: Interferon-β

  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 May 2007 was completed in August 2008. A total of 159 patients were screened at 29 sites in 5 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 dose level of interferon-β (high/low).

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.

118 participants were randomized.


Reporting Groups
  Description
Placebo + IFN-β Placebo (for teriflunomide) once daily concomitantly with interferon-β (IFN-β) for 24 weeks
Teriflunomide 7 mg + IFN-β Teriflunomide 7 mg once daily concomitantly with interferon-β (IFN-β) for 24 weeks
Teriflunomide 14 mg + IFN-β Teriflunomide 14 mg once daily concomitantly with interferon-β (IFN-β) for 24 weeks

Participant Flow:   Overall Study
    Placebo + IFN-β   Teriflunomide 7 mg + IFN-β   Teriflunomide 14 mg + IFN-β
STARTED   41 [1]   37 [1]   40 [1] 
Treated   41   36   39 [2] 
COMPLETED   38 [3]   32 [3]   37 [3] 
NOT COMPLETED   3   5   3 
Not treated due to protocol violation                0                1                1 
Adverse Event                1                1                1 
Protocol Violation                1                0                1 
Progressive disease                0                1                0 
Participant did not wish to continue                1                1                0 
Other than above                0                1                0 
[1] randomized
[2] One participant received teriflunomide 7 mg instead of teriflunomide 14 mg
[3] completed treatment period



  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 + IFN-β Placebo (for teriflunomide) once daily concomitantly with interferon-β (IFN-β) for 24 weeks
Teriflunomide 7 mg + IFN-β Teriflunomide 7 mg once daily concomitantly with interferon-β (IFN-β) for 24 weeks
Teriflunomide 14 mg + IFN-β Teriflunomide 14 mg once daily concomitantly with interferon-β (IFN-β) for 24 weeks
Total Total of all reporting groups

Baseline Measures
   Placebo + IFN-β   Teriflunomide 7 mg + IFN-β   Teriflunomide 14 mg + IFN-β   Total 
Overall Participants Analyzed 
[Units: Participants]
 41   37   38   116 
Age [1] 
[Units: Years]
Mean (Standard Deviation)
 39.2  (9.0)   41.4  (6.8)   39.6  (8.1)   40.1  (8.0) 
[1] Baseline characteristics of the population included in the analyses: the 2 participants not treated were not included, and the participant who received teriflunomide 7 mg instead of teriflunomide 14 mg was included in the teriflunomide 7 mg group.
Gender 
[Units: Participants]
       
Female   31   25   25   81 
Male   10   12   13   35 
Region of Enrollment [1] 
[Units: Participants]
       
Europe   28   25   24   77 
North America   13   12   14   39 
[1]

Europe: Germany, Italy and Spain

North America: Canada and United States

Time since first diagnosis of Multiple Sclerosis (MS) 
[Units: Years]
Mean (Standard Deviation)
 8.78  (5.62)   8.35  (5.44)   7.97  (6.59)   8.38  (5.86) 
Number of MS relapses 
[Units: MS relapses]
Median (Full Range)
       
Within the past year   1 
 (0 to 4) 
 0 
 (0 to 3) 
 1 
 (0 to 3) 
 1 
 (0 to 4) 
Within the past 2 years   1 
 (0 to 5) 
 1 
 (0 to 5) 
 1 
 (0 to 4) 
 1 
 (0 to 5) 
Time since most recent MS relapse onset 
[Units: Months]
Mean (Standard Deviation)
 27.68  (38.49)   28.97  (34.06)   24.71  (35.97)   27.12  (36.03) 
MS subtype 
[Units: Participants]
       
Relapsing Remitting   38   30   34   102 
Secondary Progressive   2   2   3   7 
Progressive Relapsing   1   5   1   7 
Baseline Expanded Disability Status Scale (EDSS) score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 2.61  (1.26)   2.41  (1.44)   2.46  (1.57)   2.50  (1.41) 
[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).

Dose level of interferon-β [1] 
[Units: Participants]
       
High dose   28   25   24   77 
Low dose   13   12   14   39 
[1]

'High dose': Rebif® 44 μg 3 times per week subcutaneously and, Betaseron® 0.25 mg every other day subcutaneously

'Low dose': Rebif® 22 μg 3 times per week subcutaneously and, Avonex® 30 μg once a week intramuscularly



  Outcome Measures

1.  Primary:   Overview of Adverse Events [AE]   [ Time Frame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) ]

2.  Primary:   Overview of AE With Potential Risk of Occurrence   [ Time Frame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) ]

3.  Primary:   Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)   [ Time Frame: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) ]

4.  Secondary:   Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)   [ Time Frame: baseline (before randomization) and 24 weeks ]

5.  Secondary:   Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)   [ Time Frame: 24 weeks ]

6.  Secondary:   Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan   [ Time Frame: 24 weeks ]

7.  Secondary:   Annualized Relapse Rate [ARR]: Poisson Regression Estimates   [ Time Frame: 24 weeks ]

8.  Secondary:   Pharmacokinetic [PK]: Teriflunomide Plasma Concentration   [ Time Frame: 24 weeks ]


  Serious Adverse Events


  Other Adverse Events


  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

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:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00489489     History of Changes
Other Study ID Numbers: PDY6045
2006-003134-14 ( EudraCT Number )
HMR1726D-2003 ( Other Identifier: HMR )
First Submitted: June 20, 2007
First Posted: June 21, 2007
Results First Submitted: October 3, 2012
Results First Posted: November 2, 2012
Last Update Posted: November 6, 2012