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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01487096
First received: December 5, 2011
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

The primary objective of this study was to determine the safety and efficacy of teriflunomide in multiple sclerosis (MS) with relapses.

Secondary objectives were:

  • To determine the effect of teriflunomide on additional magnetic resonance imaging (MRI) variables as well as clinical and quality of life measures.
  • To investigate the pharmacokinetic and pharmacodynamic relationships.

Condition Intervention Phase
Multiple Sclerosis
Drug: Teriflunomide
Drug: Placebo (placebo for teriflunomide)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Study of the Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • MRI assessment: number of unique active lesions per scan (T2/proton density and gadolinium-enhanced T1 scan analysis) [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]

    The number of unique active lesions per scan was calculated by dividing the sum of unique newly active lesions and unique persistently active lesions observed on treatment by the number of scans performed on treatment.

    Unique newly active lesions were all unique T1 and T2 lesions identified, one or more times, in a scan but not in the previous scan and, that had not been classified as unique newly active in any previous scan.

    Unique persistently active lesions were all unique T1 and T2 lesions identified, one or more times, in a scan and also in the previous scan.


  • Overview of Adverse Events [AE] [ Time Frame: from first study drug intake up to 6 weeks after last intake or entry in the extension study, whichever came first ] [ Designated as safety issue: Yes ]
    AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.


Secondary Outcome Measures:
  • MRI assessment: number of T1-enhancing lesions per scan [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]

    T1-enhancing lesions included:

    • Newly enhancing T1 lesions: lesions enhanced on the current T1 scan but not enhanced in any previous T1 scan.
    • Persistently enhancing T1 lesions: lesions enhanced on the current T1 scan and enhanced on the previous T1 scan.

  • MRI assessment: number of T2-lesions per scan [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]

    T2-lesions included:

    • New T2-lesions: lesions that appeared on the current T2 scan but were not visible on any previous T2 scans.
    • Newly enlarging T2-lesions: lesions that appeared enlarged on the current T2 scan but were stable on the previous T2 scan.
    • Persistently enlarging T2-lesions: further enlarged lesions on the current T2 scan categorized as new or enlarging on the previous T2 scan.

  • MRI assessment: Number of participants with no new lesions [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
    New lesions included new T2 lesions, new enhanced T1 lesions and unique newly active lesions.

  • MRI assessment: Change from baseline in T2 burden of disease [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
    T2 burden of disease was defined as the total volume of all T2 lesions.

  • Number of participants with progression on Expanded Disability Status Scale [EDSS] [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]

    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).

    Progression was defined as an increase in EDSS score by at least 1-point when baseline EDSS score ≤5.5 or an increase in EDSS score by at least 0.5-point in when baseline EDSS score >5.5.


  • Number of participants with MS relapse confirmed by Scripps Neurological Rating Scale [NRS] and EDSS scores. [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]

    A relapse was defined as the appearance, reappearance or worsening of a symptom attributable to MS. The change had to persist for at least 48 hours in the absence of fever and be preceded by stability or improvement for at least 30 days. Relapses were to be confirmed by Scripps NRS and EDSS scores.

    NRS is a scale that qualifies the degree of impairment from a neurological exam of the following systems: mentation and mood, cranial nerves, motor nerves, deep tendon reflexes, sensory nerves, cerebellum, gait/trunk/balance, bladder/bowel/sexual dysfunction.

    NRS score ranges from 0 to 100 (lower degree of impairment).



Enrollment: 179
Study Start Date: April 2001
Study Completion Date: March 2003
Primary Completion Date: March 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

Placebo (for teriflunomide),

  • two tablets once daily for 1 week then,
  • one tablet once daily for 35 weeks.
Drug: Placebo (placebo for teriflunomide)

film-coated tablet

oral administration

Experimental: Teriflunomide 7 mg

Teriflunomide 7 mg:

  • two tablets once daily for 1 week then,
  • one tablet once daily for 35 weeks.
Drug: Teriflunomide

film-coated tablet

oral administration

Other Name: HMR1726
Experimental: Teriflunomide 14 mg

Teriflunomide 14 mg:

  • two tablets once daily for 1 week then,
  • one tablet once daily for 35 weeks.
Drug: Teriflunomide

film-coated tablet

oral administration

Other Name: HMR1726

Detailed Description:

The total duration of the study period per participants was 46 weeks comprising 3 periods:

  • a 4-week screening period,
  • a 36-week double-blind treatment period,
  • a 6-week post-treatment follow-up period.

Participants who successfully completed the double-blind treatment phase were offered the possibility to continue study treatment in the extension study LTS6048 - NCT00228163.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinically confirmed multiple sclerosis [MS];
  • Expanded Disability Status Scale [EDSS] score less or equal to 6;
  • Two documented relapses in the previous 3 years, and one clinical relapse during the preceding year;
  • Screening magnetic resonance imaging [MRI] scan fulfilling the criteria for a diagnosis of MS.

Exclusion Criteria:

  • Clinically relevant cardiovascular, hepatic, hematologic, neurological, endocrine or other major systemic disease;
  • Pregnant or nursing woman;
  • Wish to parent children during the trial or following the trial (men and women were required to practice effective contraception during the trial and for 24 months after drug discontinuation);
  • Prior treatment with interferon [IFN], gamma-globulin, glatiramer acetate, or other noncorticosteroid immunomodulatory therapies in the 4 months prior to the trial;
  • 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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01487096

Locations
Canada, Ontario
Canada
Toronto, Ontario, Canada
France
sanofi-aventis France
Lyon, France
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Study Director Clinical Science & Operation - sanofi-aventis
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01487096     History of Changes
Other Study ID Numbers: HMR1726D/2001
Study First Received: December 5, 2011
Last Updated: October 3, 2012
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014