Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 1 of 1 for:    sanofi teracles
Previous Study | Return to List | Next Study

Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis and Treated With Interferon-beta (TERACLES)

This study has been terminated.
(Sponsor decision to prematurely stop the study, not linked to any safety concern.)
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01252355
First received: November 30, 2010
Last updated: May 30, 2014
Last verified: May 2014
Results First Received: April 23, 2014  
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 Relapse
Interventions: Drug: Teriflunomide
Drug: Placebo (for teriflunomide)
Drug: Interferon-beta (IFN-beta)

  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 January 2011, was discontinued in December 2012 following the decision of the Sponsor to discontinue the study, the common treatment end date was defined as February 28th, 2013 (treatment duration between 24 and 108 weeks).

A total of 846 participants were screened at 185 sites in 28 countries.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified by investigational site and Interferon-beta (IFN-beta) dose level (high/low). Assignment to groups was done centrally using an Interactive Voice Response System (IVRS) in a 1:1:1 ratio after confirmation of selection criteria. A total of 534 participants were randomized.

Reporting Groups
  Description
Placebo + IFN-beta Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg + IFN-beta Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg + IFN-beta Teriflunomide 14 mg once daily concomitantly with IFN-beta.

Participant Flow:   Overall Study
    Placebo + IFN-beta     Teriflunomide 7 mg + IFN-beta     Teriflunomide 14 mg + IFN-beta  
STARTED     177 [1]   178 [1]   179 [1]
Treated     175     178     179 [2]
COMPLETED     0     0     0  
NOT COMPLETED     177     178     179  
Adverse Event                 9                 17                 22  
Lack of Efficacy                 6                 4                 2  
Lost to Follow-up                 0                 0                 1  
Poor Compliance to Protocol                 1                 1                 1  
Progressive Disease                 2                 0                 0  
Sponsor Early Termination of Study                 149                 149                 146  
Randomized but not Treated                 2                 0                 0  
Other Than Above                 8                 7                 7  
[1] Randomized.
[2] One participant received teriflunomide 7 mg.



  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.
Randomized population: all randomized participants according to the treatment group to which they were assigned.

Reporting Groups
  Description
Placebo + IFN-beta Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg + IFN-beta Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg + IFN-beta Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Total Total of all reporting groups

Baseline Measures
    Placebo + IFN-beta     Teriflunomide 7 mg + IFN-beta     Teriflunomide 14 mg + IFN-beta     Total  
Number of Participants  
[units: participants]
  177     178     179     534  
Age  
[units: years]
Mean ± Standard Deviation
  38.3  ± 8.9     38.7  ± 9.5     37.7  ± 9.2     38.2  ± 9.2  
Gender  
[units: participants]
       
Female     113     125     114     352  
Male     64     53     65     182  
Region of Enrollment [1]
[units: participants]
       
America     33     30     37     100  
Western Europe     86     86     79     251  
Eastern Europe     51     51     56     158  
Asia, Africa and Australia     7     11     7     25  
Time Since First Diagnosis of Multiple Sclerosis (MS)  
[units: years]
Mean ± Standard Deviation
  7.0  ± 5.6     6.6  ± 5.6     6.8  ± 5.9     6.8  ± 5.7  
Number of MS Relapses [2]
[units: MS relapses]
Median ( Full Range )
       
Within the past year     1  
  ( 0 to 4 )  
  1  
  ( 0 to 3 )  
  1  
  ( 0 to 4 )  
  1  
  ( 0 to 4 )  
Within the past 2 years     2  
  ( 0 to 6 )  
  2  
  ( 0 to 8 )  
  2  
  ( 0 to 8 )  
  2  
  ( 0 to 8 )  
Time Since Most Recent MS Relapse Onset  
[units: months]
Median ( Full Range )
  5.0  
  ( 1.0 to 75.0 )  
  5.0  
  ( 1.0 to 36.0 )  
  4.0  
  ( 1.0 to 174.0 )  
  5.0  
  ( 1.0 to 174.0 )  
MS Subtype  
[units: participants]
       
Relapsing Remitting     174     173     175     522  
Secondary Progressive     2     3     4     9  
Progressive Relapsing     1     2     0     3  
Baseline Expanded Disability Status Scale (EDSS) Score [3]
[units: units on a scale]
Mean ± Standard Deviation
  2.67  ± 1.25     2.63  ± 1.37     2.64  ± 1.18     2.65  ± 1.26  
Dose Level of Interferon-beta (IFN-beta) Based on IVRS  
[units: participants]
       
High dose     120     128     120     368  
Low dose     57     50     59     166  
[1]

Due to the small sample size in some countries, the countries were pooled as follows:

  • America: Argentina, Brazil, Canada, Chile, Columbia, The United States
  • Western Europe: Austria, Belgium, Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Portugal, Spain, Sweden, The United Kingdom
  • Eastern Europe = Estonia, Greece, Hungary, Lithuania, Russian Federation, Slovakia
  • Asia, Africa and Australia = Australia, Republic of Korea, Tunisia
[2] The information was not available for one participant in the "Teriflunomide 14 mg + IFN-beta" group.
[3] EDSS is an ordinal scale in half-point increments that qualifies disability in participants 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: Up to a maximum of 108 weeks depending on time of enrollment ]

2.  Secondary:   Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per Scan (Poisson Regression Estimates)   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

3.  Secondary:   Time to 12-Week Sustained Disability Progression   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

4.  Secondary:   Brain MRI Assessment: Volume of Gd-enhancing T1-lesions Per MRI Scan   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

5.  Secondary:   Brain MRI Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) at Week 24   [ Time Frame: Baseline, Week 24 ]

6.  Secondary:   Time to Relapse: Kaplan-Meier Estimates of the Probability of no Relapse at Week 24, 48, and 72   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

7.  Secondary:   Change From Baseline in Fatigue Impact Scale (FIS) Total Score at Week 24   [ Time Frame: Baseline, Week 24 ]

8.  Secondary:   Change From Baseline in Short Form Generic Health Survey - 36 Items, Version 2 (SF-36v2) Summary Scores at Week 24   [ Time Frame: Baseline, Week 24 ]

9.  Secondary:   Resource Utilization When Relapse   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

10.  Secondary:   Overview of Adverse Events (AEs)   [ Time Frame: First study drug intake up to 28 days after last study drug intake, for up to 112 weeks ]

11.  Other Pre-specified:   Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)   [ Time Frame: First study drug intake up to 28 days after last study drug intake, for up to 112 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
The early termination of study with reduced sample size and participant follow-up impacts the power and interpretability, and limits the ability to assess the overall benefit/risk of adjunctive therapy. Termination was not due to any safety concerns.


  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
e-mail: Contact-us@sanofi.com


No publications provided


Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01252355     History of Changes
Other Study ID Numbers: EFC6058, 2010-023172-12, U1111-1115-2414
Study First Received: November 30, 2010
Results First Received: April 23, 2014
Last Updated: May 30, 2014
Health Authority: United States: Food and Drug Administration