Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00622700
First received: February 14, 2008
Last updated: January 20, 2017
Last verified: January 2017
Results First Received: November 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Participant, Investigator;   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Teriflunomide
Drug: Placebo

  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
A total of 846 participants were screened, of which 618 randomized in core treatment period. Out of 618, 423 entered in extension treatment period. End date of core treatment period was 17 December 2012 (maximum treatment duration: 120 weeks). End date of extension treatment period was 05 February 2016 (maximum treatment duration: 283 weeks).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized in 1:1:1 ratio to teriflunomide 7 mg,14 mg or placebo in core treatment period. Those completing core period, given opportunity to enter long-term extension period (participants originally given placebo re-randomized [1:1]to teriflunomide 7 mg/14 mg; those originally given 7 mg,14 mg continued with the same fixed dose).

Reporting Groups
  Description
Placebo Core treatment period: Placebo matched to teriflunomide tablet once daily orally.
Teriflunomide 7 mg Core treatment period: Teriflunomide 7 mg tablet once daily orally.
Teriflunomide 14 mg Core treatment period: Teriflunomide 14 mg tablet once daily orally.
Placebo/ Teriflunomide 7 mg

Core treatment period: Placebo matched to teriflunomide tablet once daily orally.

Extension treatment period: Teriflunomide 7 mg tablet once daily orally.

Teriflunomide 7 mg/7 mg

Core treatment period: Teriflunomide 7 mg tablet once daily orally.

Extension treatment period: Teriflunomide 7 mg tablet once daily orally.

Placebo/Teriflunomide 14 mg

Core treatment period: Placebo matched to teriflunomide tablet once daily orally.

Extension treatment period: Teriflunomide 14 mg tablet once daily orally.

Teriflunomide 14 mg/14 mg

Core treatment period: Teriflunomide 14 mg tablet once daily orally.

Extension treatment period: Teriflunomide 14 mg tablet once daily orally.


Participant Flow for 2 periods

Period 1:   Core Treatment Period
    Placebo   Teriflunomide 7 mg   Teriflunomide 14 mg   Placebo/ Teriflunomide 7 mg   Teriflunomide 7 mg/7 mg   Placebo/Teriflunomide 14 mg   Teriflunomide 14 mg/14 mg
STARTED   197   205   216   0   0   0   0 
Treated   197   203   214   0   0   0   0 
COMPLETED   141   150   163   0   0   0   0 
NOT COMPLETED   56   55   53   0   0   0   0 
Randomized but Not Treated                0                2                2                0                0                0                0 
Adverse Event                18                25                18                0                0                0                0 
Lack of Efficacy                19                6                12                0                0                0                0 
Lost to Follow-up                1                1                1                0                0                0                0 
Death                1                0                0                0                0                0                0 
Progressive Disease                3                1                0                0                0                0                0 
Withdrawal by Subject                12                18                15                0                0                0                0 
Other than specified above                2                2                5                0                0                0                0 

Period 2:   Extension Treatment Period
    Placebo   Teriflunomide 7 mg   Teriflunomide 14 mg   Placebo/ Teriflunomide 7 mg   Teriflunomide 7 mg/7 mg   Placebo/Teriflunomide 14 mg   Teriflunomide 14 mg/14 mg
STARTED   0 [1]   0   0   64 [2]   142 [3]   67 [2]   150 [4] 
COMPLETED   0   0   0   43   103   50   120 
NOT COMPLETED   0   0   0   21   39   17   30 
Adverse Event                0                0                0                5                9                6                8 
Lack of Efficacy                0                0                0                2                8                1                9 
Protocol Violation                0                0                0                0                0                2                0 
Lost to Follow-up                0                0                0                0                1                0                0 
Progressive Disease                0                0                0                1                2                0                2 
Withdrawal by Subject                0                0                0                11                16                6                10 
Missing                0                0                0                2                3                1                0 
Other than specified above                0                0                0                0                0                1                1 
[1] Participants were re-randomized in a 1:1 ratio to either teriflunomide 7 mg or 14 mg treatment arm.
[2] 10 participants completed core treatment period but did not enter in extension treatment period.
[3] 8 participants completed core treatment period but did not enter in extension treatment period.
[4] 13 participants completed core treatment period but did not enter in extension 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.
Randomized population: all randomized participants according to the treatment group to which they were assigned in the core treatment period.

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 
Overall Participants Analyzed 
[Units: Participants]
 197   205   216   618 
Age 
[Units: Years]
Mean (Standard Deviation)
 32.0  (8.4)   31.6  (9.0)   32.8  (8.1)   32.7  (8.9) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      135  68.5%      130  63.4%      154  71.3%      419  67.8% 
Male      62  31.5%      75  36.6%      62  28.7%      199  32.2% 
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
  Show All Outcome Measures

1.  Primary:   Core Treatment Period: 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:   Core Treatment Period: Time to Conversion to Definite Multiple Sclerosis (DMS)   [ Time Frame: Up to a maximum of 108 weeks depending on time of enrollment ]

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

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

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

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

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

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

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

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

13.  Secondary:   Core Treatment Period: 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.  Secondary:   Extension Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)   [ Time Frame: From randomization in the core period up to 390 Weeks (Extension treatment period [maximum exposure: 283 Weeks]) ]

15.  Secondary:   Extension Treatment Period: Overview of Adverse Events (AEs)   [ Time Frame: From re-randomization up to 283 Weeks ]

16.  Other Pre-specified:   Core Treatment Period: 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
  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
e-mail: Contact-us@sanofi.com


Publications:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00622700     History of Changes
Other Study ID Numbers: EFC6260
HMR1726D-3005 ( Other Identifier: HMR )
2006-001152-12 ( EudraCT Number )
Study First Received: February 14, 2008
Results First Received: November 7, 2014
Last Updated: January 20, 2017