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

Multiple Sclerosis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00134563
• Other study ID #: EFC6049
• Secondary ID: 2004-000555-42HM
• Status: Completed
• Phase: Phase 3
• First received: August 23, 2005
• Last updated: January 2, 2013
• Start date: September 2004
• Est. completion date: July 2010

Study information

• Verified date: January 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaFrance: Ministry of HealthRussia: Pharmacological Committee, Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1088
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Teriflunomide
Film-coated tablet Oral administration
• Placebo (for teriflunomide)
Film-coated tablet Oral administration

Locations

Country	Name	City	State
Austria	Sanofi-Aventis Austria	Vienna
Canada	sanofi-aventis, Canada	Laval
Chile	Sanofi-Aventis	Santiago de Chile
Czech Republic	Sanofi-Aventis Administrative Office	Praha
Denmark	sanofi-aventis Denmark	Horsholm
Estonia	Sanofi-Aventis Administrative Office	Tallinn
Finland	sanofi-aventis Finland	Helsinki
France	sanofi-aventis France	Paris
Germany	Sanofi-Aventis Deutschland GmbH	Berlin
Italy	Sanofi-Aventis	Milano
Netherlands	Sanofi-Aventis	Gouda
Norway	Sanofi-Aventis	Lysaker
Poland	sanofi-aventis Poland	Warszawa
Portugal	Sanofi-Aventis	Porto Salvo
Russian Federation	Sanofi-Aventis	Moscow
Sweden	Sanofi-Aventis	Bromma
Switzerland	Sanofi-Aventis Switzerland	Geneva
Turkey	sanofi-aventis Turkey	Istanbul
Ukraine	Sanofi-Aventis Administrative Office	Kiev
United Kingdom	sanofi-aventis UK	Guildford	Surrey
United States	Sanofi-Aventis	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Chile,  Czech Republic,  Denmark,  Estonia,  Finland,  France,  Germany,  Italy,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  Sweden,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)	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).	108 weeks	No
Other	Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan	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.	108 weeks	No
Primary	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	No
Secondary	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.	108 weeks	No
Secondary	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.	baseline (before randomization) and 108 weeks	No
Secondary	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).	baseline (before randomization) and 108 weeks	No