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Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis (TEMSO)

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ClinicalTrials.gov Identifier: NCT00134563
Recruitment Status : Completed
First Posted : August 25, 2005
Results First Posted : November 6, 2012
Last Update Posted : January 4, 2013
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE August 23, 2005
First Posted Date  ICMJE August 25, 2005
Results First Submitted Date  ICMJE October 3, 2012
Results First Posted Date  ICMJE November 6, 2012
Last Update Posted Date January 4, 2013
Study Start Date  ICMJE September 2004
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2012)
Annualized Relapse Rate [ARR]: Poisson Regression Estimates [ Time Frame: 108 weeks ]
ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations. 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 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 baseline EDSS stratum as covariates).
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2013)
  • Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints [ Time Frame: 108 weeks ]
    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 at 24, 48 and 108 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase. Participants free of disability progression (no disability progression observed on treatment) were censored at the date of the last on-treatment EDSS evaluation. 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. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.
  • Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) [ Time Frame: baseline (before randomization) and 108 weeks ]
    Total lesion volume is the sum of the total volume of all T2-lesions and the total volume all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis.
  • Changes From Baseline in Fatigue Impact Scale [FIS] Total Score [ Time Frame: baseline (before randomization) and 108 weeks ]
    FIS is a subject-reported scale that qualifies the impact of fatigue on daily life in patients with MS. It consists of 40 statements that measure fatigue in three areas; physical, cognitive, and social. FIS total score ranges from 0 (no problem) to 160 (extreme problem). Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: October 3, 2012)
  • Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) [ Time Frame: 108 weeks ]
    Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study. 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, baseline EDSS stratum and baseline number of Gd-enhancing T1-lesions as covariates).
  • Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan [ Time Frame: 108 weeks ]
    Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Design Study to Evaluate the Efficacy and Safety of Teriflunomide in Reducing the Frequency of Relapses and Delaying the Accumulation of Physical Disability in Subjects With Multiple Sclerosis With Relapses
Brief Summary

The primary objective was to determine the effect of teriflunomide on the frequency of relapses in patients with relapsing multiple sclerosis (MS).

Secondary objectives were:

  • to evaluate the effect of teriflunomide on the accumulation of disability as measured by Expanded Disability Status Scale [EDSS], the burden of disease as measured by Magnetic Resonance Imaging [MRI] and patient-reported fatigue;
  • to evaluate the safety and tolerability of teriflunomide.
Detailed Description

The study period per participant was approximatively 128 weeks broken down as follows:

  • Screening period up to 4 weeks,
  • 108-week double-blind treatment period (approximatively 2 years)*,
  • 16-week post-treatment elimination follow-up period.

'*' Participants successfully completing the week 108 visit were offered the opportunity to enter the optional long-term extension study LTS6050 - NCT00803049.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Drug: Teriflunomide

    Film-coated tablet

    Oral administration

    Other Name: HMR1726
  • Drug: Placebo (for teriflunomide)

    Film-coated tablet

    Oral administration

Study Arms  ICMJE
  • Experimental: Teriflunomide 7 mg
    Teriflunomide 7 mg once daily for 108 weeks
    Intervention: Drug: Teriflunomide
  • Experimental: Teriflunomide 14 mg
    Teriflunomide 14 mg once daily for 108 weeks
    Intervention: Drug: Teriflunomide
  • Placebo Comparator: Placebo
    Placebo (for teriflunomide) once daily for 108 weeks
    Intervention: Drug: Placebo (for teriflunomide)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 15, 2011)
1088
Original Enrollment  ICMJE
 (submitted: August 23, 2005)
870
Actual Study Completion Date  ICMJE July 2010
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Multiple sclerosis [MS] subject who was ambulatory (EDSS of ≤ 5.5)
  • Exhibiting a relapsing clinical course, with or without progression (relapsing remitting, secondary progressive or progressive relapsing);
  • Meeting McDonald's criteria for MS diagnosis;
  • Experienced at least 1 relapse over the 1 year preceding the trial or at least 2 relapses over the 2 years preceding the trial;
  • No relapse onset in the preceding 60 days prior to randomization;
  • Clinically stable during the 30 days prior to randomization, without adrenocorticotrophic hormone [ACTH] or systemic steroid treatment.

Exclusion Criteria:

  • Clinically relevant cardiovascular, hepatic, neurological, endocrine or other major systemic disease;
  • Significantly impaired bone marrow function;
  • Pregnant or nursing woman;
  • Alcohol or drug abuse;
  • Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment;
  • Any known condition or circumstance that would prevent in the investigator's opinion compliance or completion of the study;
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   Chile,   Czech Republic,   Denmark,   Estonia,   Finland,   France,   Germany,   Italy,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Sweden,   Switzerland,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00134563
Other Study ID Numbers  ICMJE EFC6049
2004-000555-42 ( EudraCT Number )
HMR1726D/3001 ( Other Identifier: HMR )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Paul O'Connor, MD St. Michael's Hospital (Toronto, Canada)
PRS Account Sanofi
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP