Back to resultsStudy of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis (TEMSO)
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Teriflunomide
Placebo (for teriflunomide)
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple Sclerosis, Relapsing Remitting, Secondary Progressive, Progressive Relapsing
Eligibility 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;
Sites / Locations
- Sanofi-Aventis
- Sanofi-Aventis Austria
- sanofi-aventis, Canada
- Sanofi-Aventis
- Sanofi-Aventis Administrative Office
- sanofi-aventis Denmark
- Sanofi-Aventis Administrative Office
- sanofi-aventis Finland
- sanofi-aventis France
- Sanofi-Aventis Deutschland GmbH
- Sanofi-Aventis
- Sanofi-Aventis
- Sanofi-Aventis
- sanofi-aventis Poland
- Sanofi-Aventis
- Sanofi-Aventis
- Sanofi-Aventis
- Sanofi-Aventis Switzerland
- sanofi-aventis Turkey
- Sanofi-Aventis Administrative Office
- sanofi-aventis UK
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Teriflunomide 7 mg
Teriflunomide 14 mg
Placebo
Arm Description
Teriflunomide 7 mg once daily for 108 weeks
Teriflunomide 14 mg once daily for 108 weeks
Placebo (for teriflunomide) once daily for 108 weeks
Outcomes
Primary Outcome Measures
Annualized Relapse Rate [ARR]: Poisson Regression Estimates
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
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)
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
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00134563
Brief Title
Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis
Acronym
TEMSO
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
September 2004 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Multiple Sclerosis, Relapsing Remitting, Secondary Progressive, Progressive Relapsing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1088 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Teriflunomide 7 mg
Arm Type
Experimental
Arm Description
Teriflunomide 7 mg once daily for 108 weeks
Arm Title
Teriflunomide 14 mg
Arm Type
Experimental
Arm Description
Teriflunomide 14 mg once daily for 108 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (for teriflunomide) once daily for 108 weeks
Intervention Type
Drug
Intervention Name(s)
Teriflunomide
Other Intervention Name(s)
HMR1726
Intervention Description
Film-coated tablet
Oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo (for teriflunomide)
Intervention Description
Film-coated tablet
Oral administration
Primary Outcome Measure Information:
Title
Annualized Relapse Rate [ARR]: Poisson Regression Estimates
Description
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).
Time Frame
108 weeks
Secondary Outcome Measure Information:
Title
Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints
Description
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.
Time Frame
108 weeks
Title
Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
Description
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.
Time Frame
baseline (before randomization) and 108 weeks
Title
Changes From Baseline in Fatigue Impact Scale [FIS] Total Score
Description
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).
Time Frame
baseline (before randomization) and 108 weeks
Other Pre-specified Outcome Measures:
Title
Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
Description
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).
Time Frame
108 weeks
Title
Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan
Description
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.
Time Frame
108 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul O'Connor, MD
Organizational Affiliation
St. Michael's Hospital (Toronto, Canada)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sanofi-Aventis
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
08807
Country
United States
Facility Name
Sanofi-Aventis Austria
City
Vienna
Country
Austria
Facility Name
sanofi-aventis, Canada
City
Laval
Country
Canada
Facility Name
Sanofi-Aventis
City
Santiago de Chile
Country
Chile
Facility Name
Sanofi-Aventis Administrative Office
City
Praha
Country
Czech Republic
Facility Name
sanofi-aventis Denmark
City
Horsholm
Country
Denmark
Facility Name
Sanofi-Aventis Administrative Office
City
Tallinn
Country
Estonia
Facility Name
sanofi-aventis Finland
City
Helsinki
Country
Finland
Facility Name
sanofi-aventis France
City
Paris
Country
France
Facility Name
Sanofi-Aventis Deutschland GmbH
City
Berlin
Country
Germany
Facility Name
Sanofi-Aventis
City
Milano
Country
Italy
Facility Name
Sanofi-Aventis
City
Gouda
Country
Netherlands
Facility Name
Sanofi-Aventis
City
Lysaker
Country
Norway
Facility Name
sanofi-aventis Poland
City
Warszawa
Country
Poland
Facility Name
Sanofi-Aventis
City
Porto Salvo
Country
Portugal
Facility Name
Sanofi-Aventis
City
Moscow
Country
Russian Federation
Facility Name
Sanofi-Aventis
City
Bromma
Country
Sweden
Facility Name
Sanofi-Aventis Switzerland
City
Geneva
Country
Switzerland
Facility Name
sanofi-aventis Turkey
City
Istanbul
Country
Turkey
Facility Name
Sanofi-Aventis Administrative Office
City
Kiev
Country
Ukraine
Facility Name
sanofi-aventis UK
City
Guildford
State/Province
Surrey
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
21991951
Citation
O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS; TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011 Oct 6;365(14):1293-303. doi: 10.1056/NEJMoa1014656.
Results Reference
result
PubMed Identifier
35485424
Citation
Sprenger T, Kappos L, Sormani MP, Miller AE, Poole EM, Cavalier S, Wuerfel J. Effects of teriflunomide treatment on cognitive performance and brain volume in patients with relapsing multiple sclerosis: Post hoc analysis of the TEMSO core and extension studies. Mult Scler. 2022 Oct;28(11):1719-1728. doi: 10.1177/13524585221089534. Epub 2022 Apr 29.
Results Reference
derived
PubMed Identifier
33023488
Citation
Comi G, Freedman MS, Meca-Lallana JE, Vermersch P, Kim BJ, Parajeles A, Edwards KR, Gold R, Korideck H, Chavin J, Poole EM, Coyle PK. Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis. BMC Neurol. 2020 Oct 6;20(1):364. doi: 10.1186/s12883-020-01937-4.
Results Reference
derived
PubMed Identifier
28828394
Citation
Radue EW, Sprenger T, Gaetano L, Mueller-Lenke N, Cavalier S, Thangavelu K, Panzara MA, Donaldson JE, Woodward FM, Wuerfel J, Wolinsky JS, Kappos L. Teriflunomide slows BVL in relapsing MS: A reanalysis of the TEMSO MRI data set using SIENA. Neurol Neuroimmunol Neuroinflamm. 2017 Aug 9;4(5):e390. doi: 10.1212/NXI.0000000000000390. eCollection 2017 Sep.
Results Reference
derived
PubMed Identifier
28680917
Citation
Sormani MP, Truffinet P, Thangavelu K, Rufi P, Simonson C, De Stefano N. Predicting long-term disability outcomes in patients with MS treated with teriflunomide in TEMSO. Neurol Neuroimmunol Neuroinflamm. 2017 Jun 28;4(5):e379. doi: 10.1212/NXI.0000000000000379. eCollection 2017 Sep.
Results Reference
derived
PubMed Identifier
28304217
Citation
Freedman MS, Wolinsky JS, Comi G, Kappos L, Olsson TP, Miller AE, Thangavelu K, Benamor M, Truffinet P, O'Connor PW; TEMSO and TOWER Study Groups. The efficacy of teriflunomide in patients who received prior disease-modifying treatments: Subgroup analyses of the teriflunomide phase 3 TEMSO and TOWER studies. Mult Scler. 2018 Apr;24(4):535-539. doi: 10.1177/1352458517695468. Epub 2017 Mar 17.
Results Reference
derived
PubMed Identifier
22723573
Citation
Miller AE, O'Connor P, Wolinsky JS, Confavreux C, Kappos L, Olsson TP, Truffinet P, Wang L, D'Castro L, Comi G, Freedman MS; Teriflunomide Multiple Sclerosis Trial Group. Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis. Mult Scler. 2012 Nov;18(11):1625-32. doi: 10.1177/1352458512450354. Epub 2012 Jun 21.
Results Reference
derived
Learn more about this trial
Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis
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