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

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ClinicalTrials.gov Identifier: NCT01252355
Recruitment Status : Terminated (Sponsor decision to prematurely stop the study, not linked to any safety concern.)
First Posted : December 3, 2010
Results First Posted : May 22, 2014
Last Update Posted : June 9, 2014
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 Relapse
Interventions Drug: Teriflunomide
Drug: Placebo (for teriflunomide)
Drug: Interferon-beta (IFN-beta)
Enrollment 534
Recruitment Details

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 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.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description Placebo (for teriflunomide) once daily concomitantly with IFN-beta. Teriflunomide 7 mg once daily concomitantly with IFN-beta. Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Period Title: Overall Study
Started 177 [1] 178 [1] 179 [1]
Treated 175 178 179 [2]
Completed 0 0 0
Not Completed 177 178 179
Reason Not Completed
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.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta Total
Hide Arm/Group Description Placebo (for teriflunomide) once daily concomitantly with IFN-beta. Teriflunomide 7 mg once daily concomitantly with IFN-beta. Teriflunomide 14 mg once daily concomitantly with IFN-beta. Total of all reporting groups
Overall Number of Baseline Participants 177 178 179 534
Hide Baseline Analysis Population Description
Randomized population: all randomized participants according to the treatment group to which they were assigned.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 177 participants 178 participants 179 participants 534 participants
38.3  (8.9) 38.7  (9.5) 37.7  (9.2) 38.2  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 178 participants 179 participants 534 participants
Female
113
  63.8%
125
  70.2%
114
  63.7%
352
  65.9%
Male
64
  36.2%
53
  29.8%
65
  36.3%
182
  34.1%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 177 participants 178 participants 179 participants 534 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
[1]
Measure Description:

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
Time Since First Diagnosis of Multiple Sclerosis (MS)  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 177 participants 178 participants 179 participants 534 participants
7.0  (5.6) 6.6  (5.6) 6.8  (5.9) 6.8  (5.7)
Number of MS Relapses   [1] 
Median (Full Range)
Unit of measure:  MS relapses
Number Analyzed 177 participants 178 participants 179 participants 534 participants
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)
[1]
Measure Description: The information was not available for one participant in the "Teriflunomide 14 mg + IFN-beta" group.
Time Since Most Recent MS Relapse Onset  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 177 participants 178 participants 179 participants 534 participants
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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 177 participants 178 participants 179 participants 534 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   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 177 participants 178 participants 179 participants 534 participants
2.67  (1.25) 2.63  (1.37) 2.64  (1.18) 2.65  (1.26)
[1]
Measure Description: 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).
Dose Level of Interferon-beta (IFN-beta) Based on IVRS  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 177 participants 178 participants 179 participants 534 participants
High dose 120 128 120 368
Low dose 57 50 59 166
1.Primary Outcome
Title Annualized Relapse Rate (ARR) (Poisson Regression Estimates)
Hide Description ARR is the total number of confirmed relapses that occurred during the treatment period divided by the total number of patient-years treated. Each episode of relapse (appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever) was to be confirmed by an increase in Expanded Disability Status Scale (EDSS) score or Functional System scores. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrollment and IFN-beta dose stratum, and number of relapses in the year prior to randomization as covariates).
Time Frame Up to a maximum of 108 weeks depending on time of enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized and treated participants. Participants were considered in the treatment group to which they were randomized regardless of the drug they actually received.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 175 178 179
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per patient-year
0.298
(0.206 to 0.432)
0.242
(0.152 to 0.386)
0.238
(0.162 to 0.351)
2.Secondary Outcome
Title Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per Scan (Poisson Regression Estimates)
Hide Description Number of Gd-enhancing T1-lesions per scan is the total number of Gd-enhancing T1-lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. To account for the different number of scans among participants, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as offset variable; treatment group, region of enrollment, IFN-beta dose stratum and baseline number of Gd-enhancing T1-lesions as covariates).
Time Frame Up to a maximum of 108 weeks depending on time of enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population as previously defined but including only participants who had post-baseline data.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 151 142 151
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: lesions per scan
0.542
(0.344 to 0.855)
0.257
(0.127 to 0.523)
0.158
(0.070 to 0.360)
3.Secondary Outcome
Title Time to 12-Week Sustained Disability Progression
Hide Description The 12-week sustained disability progression was defined as an increase from baseline of at least 1-point in EDSS score (at least 0.5-point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks. Probability of disability progression was to be estimated using Kaplan-Meier method.
Time Frame Up to a maximum of 108 weeks depending on time of enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data for this outcome was not analyzed because of insufficient data after early study termination.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Brain MRI Assessment: Volume of Gd-enhancing T1-lesions Per MRI Scan
Hide Description Total volume of Gd-enhancing T1-lesions per scan is the sum of the volumes of Gd-enhancing T1-lesions observed during the treatment period divided by the total number of scans performed during the treatment period.
Time Frame Up to a maximum of 108 weeks depending on time of enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population as previously defined but including only participants who had post-baseline data.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 151 142 151
Measure Type: Number
Unit of Measure: milliliters per scan
0.045 0.009 0.01
5.Secondary Outcome
Title Brain MRI Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) at Week 24
Hide Description The total lesion volume (burden of disease) is the total volumes of hyperintense on T2 plus hypointense on T1 as measured by MRI scan. Least-square means were estimated using a Mixed-effect model with repeated measures (MMRM) on cubic root transformed volume data with factors for treatment, region, IFN-beta dose stratum, visit, treatment-by-visit interaction, cubic root transformed baseline burden of disease, and baseline-by-visit interaction.
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population as previously defined but including only participants who had post-baseline data.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 142 132 141
Least Squares Mean (Standard Error)
Unit of Measure: milliliter
-0.008  (0.021) -0.011  (0.021) -0.044  (0.020)
6.Secondary Outcome
Title Time to Relapse: Kaplan-Meier Estimates of the Probability of no Relapse at Week 24, 48, and 72
Hide Description Probability of no relapse at 24, 48 and 72 weeks was estimated using Kaplan-Meier method on the time to relapse defined as the time from randomization to first EDSS confirmed relapse. Participants free of confirmed relapse (no EDSS confirmed relapse observed on treatment) were censored at the date of the last study drug intake. Kaplan-Meier method consists in computing probabilities of non-occurrence of event at any observed time of event and multiplying successive probabilities for time <=t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t.
Time Frame Up to a maximum of 108 weeks depending on time of enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population as previously defined.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 175 178 179
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability of no relapse
Percent probability of no relapse at Week 24
81.9
(75.8 to 88.0)
86.8
(81.4 to 92.1)
87.1
(81.8 to 92.3)
Percent probability of no relapse at Week 48
67.3
(58.8 to 75.8)
80.6
(73.3 to 87.8)
80.8
(73.9 to 87.7)
Percent probability of no relapse at Week 72
58.3
(45.4 to 71.2)
78.2
(69.8 to 86.6)
73.1
(62.2 to 83.9)
7.Secondary Outcome
Title Change From Baseline in Fatigue Impact Scale (FIS) Total Score at Week 24
Hide Description FIS is a participant-reported scale that qualifies the impact of fatigue on daily life in participants with MS.
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data for this outcome was not analyzed because of insufficient data after early study termination.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Change From Baseline in Short Form Generic Health Survey - 36 Items, Version 2 (SF-36v2) Summary Scores at Week 24
Hide Description SF-36 scale is a generic, self-administered, health-related quality-of-life (QOL) instrument.
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data for this outcome was not analyzed because of insufficient data after early study termination.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Resource Utilization When Relapse
Hide Description Resource utilization each time a participant experiences an MS relapse, specifically the number of hospitalizations, the number of over night spent in the hospital and number of intensive care admissions if hospitalized were to be reported.
Time Frame Up to a maximum of 108 weeks depending on time of enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data for this outcome was not analyzed because of insufficient data after early study termination.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Overview of Adverse Events (AEs)
Hide Description AEs are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Time Frame First study drug intake up to 28 days after last study drug intake, for up to 112 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population: all randomized and treated participants. Participants were included in the treatment group according to the drug actually received.The participant randomized to Teriflunomide 14 mg group who received Teriflunomide 7 mg was analyzed in the Teriflunomide 7 mg group.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 175 179 178
Measure Type: Number
Unit of Measure: participants
Any AE 119 140 140
Any Serious AE 8 13 14
Any AE Leading to Death 0 0 0
Any AE Leading to Study Drug Discontinuation 9 16 22
11.Other Pre-specified Outcome
Title Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)
Hide Description PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review. Hepatic parameters thresholds were defined as follows: Alanine Aminotransferase (ALT) >3, 5 or 10 Upper Limit of Normal (ULN); Aspartate Aminotransferase (AST) >3, 5 or 10 ULN; Alkaline Phosphatase >1.5 ULN; Total Bilirubin (TB) >1.5 ULN; and ALT >3 ULN and TB >2 ULN.
Time Frame First study drug intake up to 28 days after last study drug intake, for up to 112 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population as previously defined but including only participants who had post-baseline values.
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with IFN-beta.
Teriflunomide 7 mg once daily concomitantly with IFN-beta.
Teriflunomide 14 mg once daily concomitantly with IFN-beta.
Overall Number of Participants Analyzed 174 179 178
Measure Type: Number
Unit of Measure: participants
ALT >3 ULN 6 9 9
ALT >5 ULN 1 6 5
ALT >10 ULN 1 3 2
AST >3 ULN 3 4 4
AST >5 ULN 2 3 3
AST >10 ULN 1 2 0
Alkaline Phosphatase >1.5 ULN 0 2 0
TB >1.5 ULN 2 0 2
ALT >3 ULN and TB >2 ULN 0 0 0
Time Frame All AEs were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit.
Adverse Event Reporting Description The analysis was performed on the safety population and included all AEs that developed or worsened from first study drug intake up to 28 days after last study drug intake, for up to 112 weeks. Participants were included in the treatment group according to the drug actually received.
 
Arm/Group Title Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Hide Arm/Group Description Placebo (for teriflunomide) once daily concomitantly with IFN-beta. Teriflunomide 7 mg once daily concomitantly with IFN-beta. Teriflunomide 14 mg once daily concomitantly with IFN-beta.
All-Cause Mortality
Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/175 (4.57%)   13/179 (7.26%)   14/178 (7.87%) 
Blood and lymphatic system disorders       
Neutropenia  1  2/175 (1.14%)  0/179 (0.00%)  1/178 (0.56%) 
Thrombocytopenia  1  1/175 (0.57%)  0/179 (0.00%)  0/178 (0.00%) 
Cardiac disorders       
Myocardial infarction  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Supraventricular tachycardia  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Umbilical hernia  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
General disorders       
Chest pain  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Hepatobiliary disorders       
Cholelithiasis  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Drug-induced liver injury  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Hepatotoxicity  1  1/175 (0.57%)  0/179 (0.00%)  0/178 (0.00%) 
Infections and infestations       
Cystitis  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Injury, poisoning and procedural complications       
Facial bones fracture  1  1/175 (0.57%)  0/179 (0.00%)  0/178 (0.00%) 
Humerus fracture  1  1/175 (0.57%)  0/179 (0.00%)  0/178 (0.00%) 
Overdose  1  1/175 (0.57%)  0/179 (0.00%)  0/178 (0.00%) 
Thermal burn  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  0/175 (0.00%)  2/179 (1.12%)  2/178 (1.12%) 
Aspartate aminotransferase increased  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc disorder  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Testicular seminoma (pure)  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Nervous system disorders       
Convulsion  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Loss of consciousness  1  1/175 (0.57%)  0/179 (0.00%)  0/178 (0.00%) 
Multiple sclerosis  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Multiple sclerosis relapse  1  1/175 (0.57%)  2/179 (1.12%)  1/178 (0.56%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Pregnancy  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Psychiatric disorders       
Anxiety  1  1/175 (0.57%)  0/179 (0.00%)  0/178 (0.00%) 
Depression  1  1/175 (0.57%)  0/179 (0.00%)  0/178 (0.00%) 
Major depression  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Reproductive system and breast disorders       
Menorrhagia  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Ovarian cyst  1  0/175 (0.00%)  0/179 (0.00%)  1/178 (0.56%) 
Vascular disorders       
Hypertension  1  0/175 (0.00%)  1/179 (0.56%)  0/178 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + IFN-beta Teriflunomide 7 mg + IFN-beta Teriflunomide 14 mg + IFN-beta
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   85/175 (48.57%)   94/179 (52.51%)   104/178 (58.43%) 
Blood and lymphatic system disorders       
Neutropenia  1  4/175 (2.29%)  8/179 (4.47%)  10/178 (5.62%) 
Gastrointestinal disorders       
Diarrhoea  1  6/175 (3.43%)  16/179 (8.94%)  20/178 (11.24%) 
Nausea  1  9/175 (5.14%)  18/179 (10.06%)  12/178 (6.74%) 
General disorders       
Influenza like illness  1  8/175 (4.57%)  9/179 (5.03%)  4/178 (2.25%) 
Infections and infestations       
Gastroenteritis  1  0/175 (0.00%)  1/179 (0.56%)  9/178 (5.06%) 
Nasopharyngitis  1  20/175 (11.43%)  21/179 (11.73%)  20/178 (11.24%) 
Upper respiratory tract infection  1  12/175 (6.86%)  9/179 (5.03%)  9/178 (5.06%) 
Urinary tract infection  1  5/175 (2.86%)  10/179 (5.59%)  4/178 (2.25%) 
Investigations       
Alanine aminotransferase increased  1  15/175 (8.57%)  16/179 (8.94%)  26/178 (14.61%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  9/175 (5.14%)  8/179 (4.47%)  7/178 (3.93%) 
Nervous system disorders       
Dizziness  1  5/175 (2.86%)  8/179 (4.47%)  9/178 (5.06%) 
Headache  1  14/175 (8.00%)  19/179 (10.61%)  22/178 (12.36%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  9/175 (5.14%)  11/179 (6.15%)  18/178 (10.11%) 
Vascular disorders       
Hypertension  1  8/175 (4.57%)  7/179 (3.91%)  15/178 (8.43%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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.
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.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01252355     History of Changes
Other Study ID Numbers: EFC6058
2010-023172-12 ( EudraCT Number )
U1111-1115-2414 ( Other Identifier: UTN )
First Submitted: November 30, 2010
First Posted: December 3, 2010
Results First Submitted: April 23, 2014
Results First Posted: May 22, 2014
Last Update Posted: June 9, 2014