NCT00134563

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,088

participants targeted

Target at P75+ for phase_3 multiple-sclerosis

Timeline
Completed

Started Sep 2004

Longer than P75 for phase_3 multiple-sclerosis

Geographic Reach
21 countries

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2004

Completed
12 months until next milestone

First Submitted

Initial submission to the registry

August 23, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 25, 2005

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2010

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

November 6, 2012

Completed
Last Updated

January 4, 2013

Status Verified

January 1, 2013

Enrollment Period

5.8 years

First QC Date

August 23, 2005

Results QC Date

October 3, 2012

Last Update Submit

January 2, 2013

Conditions

Multiple Sclerosis

Keywords

Multiple SclerosisRelapsing RemittingSecondary ProgressiveProgressive Relapsing

Outcome Measures

Primary Outcomes (1)

  • 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).

    108 weeks

Secondary Outcomes (3)

  • Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints

    108 weeks

  • Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)

    baseline (before randomization) and 108 weeks

  • Changes From Baseline in Fatigue Impact Scale [FIS] Total Score

    baseline (before randomization) and 108 weeks

Other Outcomes (2)

  • Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)

    108 weeks

  • Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan

    108 weeks

Study Arms (3)

Teriflunomide 7 mg

EXPERIMENTAL

Teriflunomide 7 mg once daily for 108 weeks

Drug: Teriflunomide

Teriflunomide 14 mg

EXPERIMENTAL

Teriflunomide 14 mg once daily for 108 weeks

Drug: Teriflunomide

Placebo

PLACEBO COMPARATOR

Placebo (for teriflunomide) once daily for 108 weeks

Drug: Placebo (for teriflunomide)

Interventions

TeriflunomideDRUG

Film-coated tablet Oral administration

Also known as: HMR1726
Teriflunomide 14 mgTeriflunomide 7 mg
Placebo (for teriflunomide)DRUG

Film-coated tablet Oral administration

Placebo

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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;

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Sanofi-Aventis

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis Austria

Vienna, Austria

Location

sanofi-aventis, Canada

Laval, Canada

Location

Sanofi-Aventis

Santiago, Chile

Location

Sanofi-Aventis Administrative Office

Prague, Czechia

Location

sanofi-aventis Denmark

Hørsholm, Denmark

Location

Sanofi-Aventis Administrative Office

Tallinn, Estonia

Location

sanofi-aventis Finland

Helsinki, Finland

Location

sanofi-aventis France

Paris, France

Location

Sanofi-Aventis Deutschland GmbH

Berlin, Germany

Location

Sanofi-Aventis

Milan, Italy

Location

Sanofi-Aventis

Gouda, Netherlands

Location

Sanofi-Aventis

Lysaker, Norway

Location

sanofi-aventis Poland

Warsaw, Poland

Location

Sanofi-Aventis

Porto Salvo, Portugal

Location

Sanofi-Aventis

Moscow, Russia

Location

Sanofi-Aventis

Bromma, Sweden

Location

Sanofi-Aventis Switzerland

Geneva, Switzerland

Location

sanofi-aventis Turkey

Istanbul, Turkey (Türkiye)

Location

Sanofi-Aventis Administrative Office

Kiev, Ukraine

Location

sanofi-aventis UK

Guildford, Surrey, United Kingdom

Location

Related Publications (7)

  • 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.

    PMID: 21991951RESULT

  • 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.

    PMID: 35485424DERIVED

  • 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.

    PMID: 33023488DERIVED

  • 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.

    PMID: 28828394DERIVED

  • 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.

    PMID: 28680917DERIVED

  • 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.

    PMID: 28304217DERIVED

  • 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.

    PMID: 22723573DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

teriflunomide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Results Point of Contact

Title
Trial Transparency Team
Organization
sanofi-aventis
Contact_US@sanofi-aventis.com

Study Officials

  • Paul O'Connor, MD

    St. Michael's Hospital (Toronto, Canada)

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 23, 2005

First Posted

August 25, 2005

Study Start

September 1, 2004

Primary Completion

July 1, 2010

Study Completion

July 1, 2010

Last Updated

January 4, 2013

Results First Posted

November 6, 2012

Record last verified: 2013-01

Locations

NO(1)ES(1)CA(1)CZ(1)FR(1)US(1)NL(1)PT(1)FI(1)GB(1)IT(1)DE(1)PL(1)RU(1)UA(1)SE(1)AU(1)CH(1)CL(1)TU(1)DK(1)