Clinical trial NCT00228163: Long Term Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Official title: Extension of Protocol HMR1726D/2001, A Phase II Study of the Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis Relapsing Remitting
Secondary Progressive
Progressive Relapsing
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-09-28
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: 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
Secondary outcomes:
measure: Annualized relapse rate (number of relapses per patient-year)
timeFrame: 528 weeks or until teriflunomide is commercially available in the country where patient lives
measure: Change from baseline in Kurtzke Expanded Disability Status Scale (EDSS) score
timeFrame: 528 weeks or until teriflunomide is commercially available in the country where patient lives
measure: Change from baseline in Multiple Sclerosis Functional Composite (MSFC) score
timeFrame: 528 weeks or until teriflunomide is commercially available in the country where patient lives
measure: Burden of disease : Change from baseline in the volume of abnormal brain tissue as measured by brain Magnetic Resonance Image (MRI)
timeFrame: 528 weeks or until teriflunomide is commercially available in the country where patient lives
measure: Change from baseline in Multiple Sclerosis Quality of Life Questionnaire-54 (MSQoL-54) score
timeFrame: 528 weeks or until teriflunomide is commercially available in the country where patient lives
measure: Change from baseline in subject reported fatigue as assessed by the Fatigue Impact Scale (FIS)
timeFrame: 528 weeks or until teriflunomide is commercially available in the country where patient lives
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Investigational Site Number 16
city: Halifax
country: Canada
facility: Investigational Site Number 10
city: London
country: Canada
facility: Investigational Site Number 15
city: Montreal
country: Canada
facility: Investigational Site Number 12
city: Montreal
country: Canada
facility: Investigational Site Number 11
city: Ottawa
country: Canada
facility: Investigational Site Number 13
city: Quebec
country: Canada
facility: Investigational Site Number 18
city: Toronto
country: Canada
facility: Investigational Site Number 14
city: Vancouver
country: Canada
facility: Investigational Site Number 17
city: Winnipeg
country: Canada
facility: Investigational Site Number 19
city: Clermont Ferrand Cedex 1
country: France
facility: Investigational Site Number 24
city: Lyon Cedex 03
country: France
facility: Investigational Site Number 21
city: Marseille Cedex 5
country: France
facility: Investigational Site Number 30
city: Montpellier Cedex 5
country: France
facility: Investigational Site Number 23
city: Nice Cedex
country: France
facility: Investigational Site Number 28
city: Rennes Cedex
country: France
facility: Investigational Site Number 27
Study officials:
affiliation: St. Michael's Hospital, 30 Bond Street, 3rd floor, Toronto, ON M5B 1W8, Canada
name: Paul W O'Connor, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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. doi: 10.1177/1352458512436594. Epub 2012 Feb 3.