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

Extension of Protocol HMR1726D/2001, A Phase II Study of the Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: teriflunomide (HMR1726)

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: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2N 2T9
    • Investigational Site Number 16
  • Halifax, Canada, B3H 1V7
    • Investigational Site Number 10
  • London, Canada, N6A 5A5
    • Investigational Site Number 15
  • Montreal, Canada, H2L 4M1
    • Investigational Site Number 12
  • Montreal, Canada, H3A 2B4
    • Investigational Site Number 11
  • Ottawa, Canada, K1H 8L6
    • Investigational Site Number 13
  • Quebec, Canada, G1J 1Z4
    • Investigational Site Number 18
  • Toronto, Canada, M5B 1W8
    • Investigational Site Number 14
  • Vancouver, Canada, V6T 2B5
    • Investigational Site Number 17
  • Winnipeg, Canada, R3E 3N4
    • Investigational Site Number 19
• France
  • Clermont Ferrand Cedex 1, France, 63003
    • Investigational Site Number 24
  • Lyon Cedex 03, France, 69394
    • Investigational Site Number 21
  • Marseille Cedex 5, France, 13385
    • Investigational Site Number 30
  • Montpellier Cedex 5, France, 34000
    • Investigational Site Number 23
  • Nice Cedex, France, 06002
    • Investigational Site Number 28
  • Rennes Cedex, France, 35033
    • Investigational Site Number 27

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Teriflunomide 7 mg	Drug: teriflunomide (HMR1726); tablet, oral administration once daily.
Experimental: Teriflunomide 14 mg	Drug: teriflunomide (HMR1726); tablet, oral administration once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	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 Outcome Measures

Outcome Measure	Time Frame
Annualized relapse rate (number of relapses per patient-year)	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	528 weeks or until teriflunomide is commercially available in the country where patient lives
Change from baseline in Multiple Sclerosis Functional Composite (MSFC) score	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)	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	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)	528 weeks or until teriflunomide is commercially available in the country where patient lives

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Principal Investigator: Paul W O'Connor, MD, St. Michael's Hospital, 30 Bond Street, 3rd floor, Toronto, ON M5B 1W8, Canada

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: September 26, 2005
• First Submitted That Met QC Criteria: September 26, 2005
• First Posted (Estimate): September 28, 2005

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Multiple Sclerosis Relapsing Remitting; Secondary Progressive; Progressive Relapsing
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Teriflunomide
• Other Study ID Numbers: LTS6048; HMR1726D/2002