Clinical trial NCT00134563: Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Relapsing Remitting
Secondary Progressive
Progressive Relapsing
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-08-25
Enrollment: 1088
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Annualized Relapse Rate [ARR]: Poisson Regression Estimates
timeFrame: 108 weeks
Secondary outcomes:
measure: Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints
timeFrame: 108 weeks
measure: Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
timeFrame: baseline (before randomization) and 108 weeks
measure: Changes From Baseline in Fatigue Impact Scale [FIS] Total Score
timeFrame: baseline (before randomization) and 108 weeks
Other outcomes:
measure: Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
timeFrame: 108 weeks
measure: Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan
timeFrame: 108 weeks
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis
state: New Jersey
city: Vienna
country: Austria
facility: Sanofi-Aventis Austria
city: Laval
country: Canada
facility: sanofi-aventis, Canada
city: Santiago de Chile
country: Chile
facility: Sanofi-Aventis
city: Praha
country: Czech Republic
facility: Sanofi-Aventis Administrative Office
city: Horsholm
country: Denmark
facility: sanofi-aventis Denmark
city: Tallinn
country: Estonia
facility: Sanofi-Aventis Administrative Office
city: Helsinki
country: Finland
facility: sanofi-aventis Finland
city: Paris
country: France
facility: sanofi-aventis France
city: Berlin
country: Germany
facility: Sanofi-Aventis Deutschland GmbH
city: Milano
country: Italy
facility: Sanofi-Aventis
city: Gouda
country: Netherlands
facility: Sanofi-Aventis
city: Lysaker
country: Norway
facility: Sanofi-Aventis
city: Warszawa
country: Poland
facility: sanofi-aventis Poland
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis
city: Bromma
country: Sweden
facility: Sanofi-Aventis
city: Geneva
country: Switzerland
facility: Sanofi-Aventis Switzerland
city: Istanbul
country: Turkey
facility: sanofi-aventis Turkey
city: Kiev
country: Ukraine
facility: Sanofi-Aventis Administrative Office
city: Guildford
country: United Kingdom
facility: sanofi-aventis UK
state: Surrey
Study officials:
affiliation: St. Michael's Hospital (Toronto, Canada)
name: Paul O'Connor, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.