Phase III Study With Teriflunomide Versus Placebo in Patients With First Clinical Symptom of Multiple Sclerosis (TOPIC)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00622700
First received: February 14, 2008
Last updated: December 17, 2014
Last verified: December 2014
Results First Received: November 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Teriflunomide
Drug: Placebo

  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 on 13 Feb 2008, was stopped on 23 Aug 2012 following Sponsor’s decision to stop placebo-controlled period. Participants completing the placebo-controlled period, those converting to CDMS (treated at least 24 weeks) or ongoing on treatment, were given the opportunity to be included in long-term extension period.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 846 participants were screened, of these 618 participants were randomized.

Reporting Groups
  Description
Placebo Placebo matched to teriflunomide tablet once daily orally.
Teriflunomide 7 Milligram (mg) Teriflunomide 7 mg tablet once daily orally.
Teriflunomide 14 mg Teriflunomide 14 mg tablet once daily orally.

Participant Flow:   Overall Study
    Placebo     Teriflunomide 7 Milligram (mg)     Teriflunomide 14 mg  
STARTED     197 [1]   205     216  
COMPLETED     141 [2]   150 [2]   163 [2]
NOT COMPLETED     56     55     53  
Randomized but Not Treated                 0                 2                 2  
Adverse Event                 18                 25                 18  
Lack of Efficacy                 19                 6                 12  
Lost to Follow-up                 1                 1                 1  
Death                 1                 0                 0  
Progressive Disease                 3                 1                 0  
Withdrawal by Subject                 12                 18                 15  
Other Than Above                 2                 2                 5  
[1] 4 participants received teriflunomide 7 mg and 2 participants received teriflunomide 14 mg.
[2] Defined as completing 108 weeks placebo-controlled period or entering the extension 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.
Randomized population: all randomized participants according to the treatment group to which they were assigned.

Reporting Groups
  Description
Placebo Placebo matched to teriflunomide tablet once daily orally.
Teriflunomide 7 mg Teriflunomide 7 mg tablet once daily orally.
Teriflunomide 14 mg Teriflunomide 14 mg tablet once daily orally.
Total Total of all reporting groups

Baseline Measures
    Placebo     Teriflunomide 7 mg     Teriflunomide 14 mg     Total  
Number of Participants  
[units: participants]
  197     205     216     618  
Age  
[units: years]
Mean (Standard Deviation)
  32.0  (8.4)     31.6  (9.0)     32.8  (8.1)     32.1  (8.5)  
Gender  
[units: participants]
       
Female     135     130     154     419  
Male     62     75     62     199  
Region  
[units: participants]
       
Eastern Europe     94     96     101     291  
Western Europe     76     74     74     224  
Americas and Australia     27     35     41     103  
Expanded Disability Status Scale (EDSS) Score [1]
[units: units on a scale]
Mean (Standard Deviation)
  1.71  (1.00)     1.50  (1.02)     1.80  (0.97)     1.67  (1.00)  
[1] 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
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1.  Primary:   Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

2.  Secondary:   Time to Conversion to Definite Multiple Sclerosis (DMS)   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

3.  Secondary:   Annualized Relapse Rate (ARR)   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

4.  Secondary:   Brain Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Lesion Volume at Week 108   [ Time Frame: Baseline, Week 108 ]

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

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

7.  Secondary:   Brain MRI Assessment: Change From Baseline in Volume of Hypointense Post-Gadolinium T1 Lesion Component   [ Time Frame: Baseline, Week 108 ]

8.  Secondary:   Brain MRI Assessment: Change From Baseline in Volume of T2 Lesion Component   [ Time Frame: Baseline, Week 108 ]

9.  Secondary:   Brain MRI Assessment: Percent Change From Baseline in Atrophy   [ Time Frame: Baseline, Week 108 ]

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

11.  Secondary:   Change From Baseline in EDSS at Week 108   [ Time Frame: Baseline, Week 108 ]

12.  Secondary:   Change From Baseline in Fatigue Impact Scale (FIS) Total Score at Week 108   [ Time Frame: Baseline, Week 108 ]

13.  Secondary:   Overview of Adverse Events (AEs)   [ Time Frame: From first study drug intake up to 112 days after last intake in the placebo-controlled period or up to first intake in the extension treatment period, whichever occurred first ]

14.  Other Pre-specified:   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 in the placebo-controlled period or up to first intake in the extension treatment period, whichever occurred first ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  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.


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: NCT00622700     History of Changes
Other Study ID Numbers: EFC6260, HMR1726D-3005, 2006-001152-12
Study First Received: February 14, 2008
Results First Received: November 7, 2014
Last Updated: December 17, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut