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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00134563
First received: August 23, 2005
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

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.

Condition Intervention Phase
Multiple Sclerosis
Drug: Teriflunomide
Drug: Placebo (for teriflunomide)
Phase 3

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
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Annualized Relapse Rate [ARR]: Poisson Regression Estimates [ Time Frame: 108 weeks ] [ Designated as safety issue: No ]

    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).



Secondary Outcome Measures:
  • Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints [ Time Frame: 108 weeks ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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).



Other Outcome Measures:
  • Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) [ Time Frame: 108 weeks ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 1088
Study Start Date: September 2004
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Teriflunomide 7 mg
Teriflunomide 7 mg once daily for 108 weeks
Drug: Teriflunomide

Film-coated tablet

Oral administration

Other Name: HMR1726
Experimental: Teriflunomide 14 mg
Teriflunomide 14 mg once daily for 108 weeks
Drug: Teriflunomide

Film-coated tablet

Oral administration

Other Name: HMR1726
Placebo Comparator: Placebo
Placebo (for teriflunomide) once daily for 108 weeks
Drug: Placebo (for teriflunomide)

Film-coated tablet

Oral administration


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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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;
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00134563

  Show 21 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Principal Investigator: Paul O'Connor, MD St. Michael's Hospital Toronto (Canada)
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00134563     History of Changes
Other Study ID Numbers: EFC6049, 2004-000555-42, HMR1726D/3001
Study First Received: August 23, 2005
Results First Received: October 3, 2012
Last Updated: January 2, 2013
Health Authority: Canada: Health Canada
France: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
United States: Food and Drug Administration

Keywords provided by Sanofi:
Multiple Sclerosis
Relapsing Remitting
Secondary Progressive
Progressive Relapsing

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 23, 2014