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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Sanofi

ClinicalTrials.gov Identifier:

NCT00134563

First received: August 23, 2005

Last updated: January 2, 2013

Last verified: January 2013

History of Changes

Results First Received: October 3, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Multiple Sclerosis
Interventions:	Drug: Teriflunomide Drug: Placebo (for teriflunomide)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The recruitment initiated in September 2004 was completed in February 2008. A total of 1338 patients were screened at 127 sites in 21 countries.

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

The recruitment initiated in September 2004 was completed in February 2008.

A total of 1338 patients were screened at 127 sites in 21 countries.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified by country and baseline disability (Expanded Disability Status Scale [EDSS] score ≤3.5 or >3.5). Assignment to groups was done centrally using an Interactive Voice Response System (IVRS] in a 1:1:1 ratio after confirmation of the selection criteria. 1088 participants were randomized.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Randomization was stratified by country and baseline disability (Expanded Disability Status Scale [EDSS] score ≤3.5 or >3.5).

Assignment to groups was done centrally using an Interactive Voice Response System (IVRS] in a 1:1:1 ratio after confirmation of the selection criteria.

1088 participants were randomized.

Reporting Groups

	Description
Placebo	Placebo (for teriflunomide) once daily for 108 weeks
Teriflunomide 7 mg	Teriflunomide 7 mg once daily for 108 weeks
Teriflunomide 14 mg	Teriflunomide 14 mg once daily for 108 weeks

Participant Flow: Overall Study

	Placebo	Teriflunomide 7 mg	Teriflunomide 14 mg
STARTED	363 ^[1]	366 ^[1]	359 ^[1]
Treated	363 ^[2]	365	358 ^[3]
COMPLETED	259 ^[4]	274 ^[4]	263 ^[4]
NOT COMPLETED	104	92	96
Not treated due to protocol violation	0	1	1
Adverse Event	29	37	38
Lack of Efficacy	24	14	17
Protocol Violation	3	2	5
Lost to Follow-up	4	0	2
progressive disease	11	4	2
did not wish to continue	33	32	26
Reason other than above	0	2	5

[1]	Randomized
[2]	Two participants received doses of Teriflunomide 7 mg, one participant doses of Teriflunomide 14 mg
[3]	one participant received doses of Teriflunomide 7 mg
[4]	completed treatment period

Baseline Characteristics

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Reporting Groups

	Description
Placebo	Placebo (for teriflunomide) once daily for 108 weeks
Teriflunomide 7 mg	Teriflunomide 7 mg once daily for 108 weeks
Teriflunomide 14 mg	Teriflunomide 14 mg once daily for 108 weeks
Total	Total of all reporting groups

Baseline Measures

	Placebo	Teriflunomide 7 mg	Teriflunomide 14 mg	Total
Number of Participants [units: participants]	363	365	358	1086
Age ^[1] [units: years] Mean ± Standard Deviation	38.4 ± 9.0	37.5 ± 9.0	37.8 ± 8.2	37.9 ± 8.8
Gender [units: participants]
Female	275	254	254	783
Male	88	111	104	303
Region of enrollment ^[2] [units: participants]
America	82	83	80	245
Eastern Europe	114	116	108	338
Western Europe	167	166	170	503
Time since first diagnosis of multiple sclerosis (MS) ^[3] [units: Years] Mean ± Standard Deviation	5.13 ± 5.59	5.29 ± 5.36	5.59 ± 5.44	5.33 ± 5.48
Number of MS relapses [units: MS relapses] Median ( Full Range )
Within the past year	1 ( 0 to 6 )	1 ( 0 to 6 )	1 ( 0 to 4 )	1 ( 0 to 6 )
Within the past 2 years	2 ( 1 to 7 )	2 ( 1 to 12 )	2 ( 1 to 9 )	2 ( 1 to 12 )
Time since most recent MS relapse onset [units: months] Mean ± Standard Deviation	6.28 ± 3.62	6.29 ± 3.29	6.50 ± 3.71	6.35 ± 3.54
MS subtype [units: participants]
Relapsing Remitting	329	332	332	993
Secondary Progressive	22	17	12	51
Progressive Relapsing	12	16	14	42
MS medication in the past 2 years [units: participants]
Yes	90	102	102	294
No	273	263	256	792
Baseline EDSS total score ^[4] [units: participants]
≤ 3.5	281	280	276	837
> 3.5	82	85	82	249

[1]	Baseline characteristics of the population included in analyses
[2]	America: Canada, Chile, and United States; Eastern Europe: Czech Republic, Estonia, Poland, Russia and Ukraine; Western Europe: Austria, Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Portugal, Sweden, Switzerland, Turkey, and United Kingdom;
[3]	The information was missing for one participant in the Teriflunomide 7 mg group.
[4]	EDSS is an ordinal scale in half-point increments that qualifies disability in patients with MS. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS).

Outcome Measures

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1. Primary:

Annualized Relapse Rate [ARR]: Poisson Regression Estimates [ Time Frame: 108 weeks ]

Show Outcome Measure 1

2. Secondary:

Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints [ Time Frame: 108 weeks ]

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3. Secondary:

Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) [ Time Frame: baseline (before randomization) and 108 weeks ]

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4. Secondary:

Changes From Baseline in Fatigue Impact Scale [FIS] Total Score [ Time Frame: baseline (before randomization) and 108 weeks ]

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5. Other Pre-specified:

Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) [ Time Frame: 108 weeks ]

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6. Other Pre-specified:

Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan [ Time Frame: 108 weeks ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:

The investigator can publish only the results of the work performed pursuant to this protocol. Prior to publication, the investigator provides the sponsor with the manuscript for review and comment at least 45 days in advance of its submission for publication.

The sponsor can require the investigator to withhold publication an additional 90 days to allow for filing a patent application or taking such other measures as sponsor deems appropriate to establish and preserve its proprietary rights.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Trial Transparency Team
Organization: sanofi-aventis
e-mail: Contact_US@sanofi-aventis.com

Publications of Results:

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.

Publications automatically indexed to this study:

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.

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT00134563 History of Changes
Other Study ID Numbers:	EFC6049, 2004-000555-42, HMR1726D/3001
Study First Received:	August 23, 2005
Results First Received:	October 3, 2012
Last Updated:	January 2, 2013
Health Authority:	Canada: Health Canada France: Ministry of Health Russia: Pharmacological Committee, Ministry of Health United States: Food and Drug Administration

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