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

NCT ID: NCT00134563

Last Updated: 2013-01-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1088 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-09-30

Study Completion Date

2010-07-31

Brief Summary

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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

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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.

Conditions

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Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Teriflunomide 7 mg

Teriflunomide 7 mg once daily for 108 weeks

Group Type EXPERIMENTAL

Teriflunomide

Intervention Type DRUG

Film-coated tablet

Oral administration

Teriflunomide 14 mg

Teriflunomide 14 mg once daily for 108 weeks

Group Type EXPERIMENTAL

Teriflunomide

Intervention Type DRUG

Film-coated tablet

Oral administration

Placebo

Placebo (for teriflunomide) once daily for 108 weeks

Group Type PLACEBO_COMPARATOR

Placebo (for teriflunomide)

Intervention Type DRUG

Film-coated tablet

Oral administration

Interventions

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Teriflunomide

Film-coated tablet

Oral administration

Intervention Type DRUG

Placebo (for teriflunomide)

Film-coated tablet

Oral administration

Intervention Type DRUG

Other Intervention Names

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HMR1726

Eligibility Criteria

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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;
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul O'Connor, MD

Role: PRINCIPAL_INVESTIGATOR

St. Michael's Hospital (Toronto, Canada)

Locations

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Sanofi-Aventis

Bridgewater, New Jersey, United States

Site Status

Sanofi-Aventis Austria

Vienna, , Austria

Site Status

sanofi-aventis, Canada

Laval, , Canada

Site Status

Sanofi-Aventis

Santiago, , Chile

Site Status

Sanofi-Aventis Administrative Office

Prague, , Czechia

Site Status

sanofi-aventis Denmark

Hørsholm, , Denmark

Site Status

Sanofi-Aventis Administrative Office

Tallinn, , Estonia

Site Status

sanofi-aventis Finland

Helsinki, , Finland

Site Status

sanofi-aventis France

Paris, , France

Site Status

Sanofi-Aventis Deutschland GmbH

Berlin, , Germany

Site Status

Sanofi-Aventis

Milan, , Italy

Site Status

Sanofi-Aventis

Gouda, , Netherlands

Site Status

Sanofi-Aventis

Lysaker, , Norway

Site Status

sanofi-aventis Poland

Warsaw, , Poland

Site Status

Sanofi-Aventis

Porto Salvo, , Portugal

Site Status

Sanofi-Aventis

Moscow, , Russia

Site Status

Sanofi-Aventis

Bromma, , Sweden

Site Status

Sanofi-Aventis Switzerland

Geneva, , Switzerland

Site Status

sanofi-aventis Turkey

Istanbul, , Turkey (Türkiye)

Site Status

Sanofi-Aventis Administrative Office

Kiev, , Ukraine

Site Status

sanofi-aventis UK

Guildford, Surrey, United Kingdom

Site Status

Countries

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United States Austria Canada Chile Czechia Denmark Estonia Finland France Germany Italy Netherlands Norway Poland Portugal Russia Sweden Switzerland Turkey (Türkiye) Ukraine United Kingdom

References

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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.

Reference Type RESULT
PMID: 21991951 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35485424 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33023488 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28828394 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28680917 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28304217 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22723573 (View on PubMed)

Other Identifiers

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2004-000555-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HMR1726D/3001

Identifier Type: OTHER

Identifier Source: secondary_id

EFC6049

Identifier Type: -

Identifier Source: org_study_id

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