Long Term Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses

Tracking Information
First Submitted Date ICMJE	September 26, 2005
First Posted Date ICMJE	September 28, 2005
Last Update Posted Date	March 25, 2015
Study Start Date ICMJE	January 2002
Actual Primary Completion Date	January 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 3, 2012)	Number of patients with adverse events [ Time Frame: Up to a maximum of 532 weeks (4 weeks after last treatment intake) or until teriflunomide is commercially available in the country where patient lives ]
Original Primary Outcome Measures ICMJE; (submitted: September 26, 2005)	The incidence of adverse events will be measured
Change History	Complete list of historical versions of study NCT00228163 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 3, 2012)	Annualized relapse rate (number of relapses per patient-year) [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ]; Change from baseline in Kurtzke Expanded Disability Status Scale (EDSS) score [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ]; Change from baseline in Multiple Sclerosis Functional Composite (MSFC) score [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ]; Burden of disease : Change from baseline in the volume of abnormal brain tissue as measured by brain Magnetic Resonance Image (MRI) [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ]; Change from baseline in Multiple Sclerosis Quality of Life Questionnaire-54 (MSQoL-54) score [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ]; Change from baseline in subject reported fatigue as assessed by the Fatigue Impact Scale (FIS) [ Time Frame: 528 weeks or until teriflunomide is commercially available in the country where patient lives ]
Original Secondary Outcome Measures ICMJE; (submitted: September 26, 2005)	Assessment of the EDSS scores, MSFC score, Burden of disease and brain atrophy as calculated from MRI scans, annual rate of relpases and quality of life (MSQOL-54 and FIS)
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Long Term Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Official Title ICMJE	Extension of Protocol HMR1726D/2001, A Phase II Study of the Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Brief Summary	The primary objective is to assess the long-term safety of teriflunomide in multiple sclerosis subjects. The secondary objective is to assess the long-term efficacy.
Detailed Description	Subjects completing the HMR 1726D/2001 study are given the opportunity to continue or switch to teriflunomide for 528 weeks or until teriflunomide is commercially available in the country where patient lives; subjects on Teriflunomide 7 mg or 14 mg continue on the same dose of teriflunomide.; subjects on placebo are randomized to teriflunomide 7 mg or 14 mg. The total study period per subject is 532 weeks or until teriflunomide is commercially available in the country where patient lives, broken up as follows: Treatment: 528 weeks or until teriflunomide is commercially available in the country where patient lives,; Post-washout follow-up: 4 weeks after last treatment intake.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Multiple Sclerosis
Intervention ICMJE	Drug: teriflunomide (HMR1726); tablet, oral administration once daily.
Study Arms	Experimental: Teriflunomide 7 mg Intervention: Drug: teriflunomide (HMR1726); Experimental: Teriflunomide 14 mg Intervention: Drug: teriflunomide (HMR1726)
Publications *	Confavreux C, Li DK, Freedman MS, Truffinet P, Benzerdjeb H, Wang D, Bar-Or A, Traboulsee AL, Reiman LE, O'Connor PW; Teriflunomide Multiple Sclerosis Trial Group. Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years. Mult Scler. 2012 Sep;18(9):1278-89. Epub 2012 Feb 3.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: September 26, 2005)	147
Original Enrollment ICMJE	Same as current
Actual Study Completion Date	January 2015
Actual Primary Completion Date	January 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Satisfactorily completion of HMR1726D/2001 study with respect to safety.; If female subject, non-childbearing potential or child bearing potential with adequate contraception.; Consent to practice/maintain adequate means of contraception throughout the study and for 24 months after the discontinuation of treatment.; Clinically definite Multiple Sclerosis (MS) as established on entry into HMR1726D/2001 study.; Extended Disability Status Score(EDSS) between 0 and 6 inclusively, when the subject entered HMR1726D/2001 study.; Magnetic Resonance Imaging (MRI) criteria must continue to support the diagnosis of clinically definite MS.; Willingness to participate in a long-term safety and efficacy trial. Exclusion Criteria: Subject who did not complete HMR 1726D/2001 study for safety reasons.; Subject who developed clinically relevant cardiovascular, hepatic, endocrine or other major disease.; Pregnancy.; Breast-feeding.; Wish to parent.; Likelihood of requiring treatment during the study period with drugs not permitted.; Disallowed therapies such asw immunomodulators, immunosuppressants.; Recent history of drug or alcohol abuse.; Liver function impairment.; Abnormal mental conditions.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 65 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada, France
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00228163
Other Study ID Numbers ICMJE	LTS6048; HMR1726D/2002
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Sanofi
Study Sponsor ICMJE	Sanofi
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Paul W O'Connor, MD St. Michael's Hospital, 30 Bond Street, 3rd floor, Toronto, ON M5B 1W8, Canada
PRS Account	Sanofi
Verification Date	March 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP