Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01487096
Recruitment Status : Completed
First Posted : December 7, 2011
Last Update Posted : October 4, 2012
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE December 5, 2011
First Posted Date  ICMJE December 7, 2011
Last Update Posted Date October 4, 2012
Study Start Date  ICMJE April 2001
Actual Primary Completion Date March 2003   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2012)
  • MRI assessment: number of unique active lesions per scan (T2/proton density and gadolinium-enhanced T1 scan analysis) [ Time Frame: 36 weeks ]
    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 ]
    AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2011)
  • MRI assessment: number of unique active lesions per scan (T2/proton density and gadolinium-enhanced T1 scan analysis) [ Time Frame: Up to 36 weeks from randomization ]
    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.
  • Number of participants with Adverse Events (AE) [ Time Frame: Up to a maximum of 46 weeks from signature of the inform consent form ]
    AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. Participants who experienced AE during the 'on treatment period' (i.e. from first study drug intake up to 6 weeks after last study drug intake or entry in the extension study, whichever came first) were counted.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2012)
  • MRI assessment: number of T1-enhancing lesions per scan [ Time Frame: 36 weeks ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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).
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2011)
  • MRI assessment: number of T1-enhancing lesions per scan [ Time Frame: Up to 36 weeks from randomization ]
    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: Up to 36 weeks from randomization ]
    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: Up to 36 weeks from randomization ]
    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 from randomization ]
    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: Up to 36 weeks from randomization ]
    EDSS qualifies disability from 0 (normal neurologic exam) to 10 (death due to MS) in half-point increments from the neurological testing of the following functions: pyramidal (ability to walk), cerebellar (coordination), brainstem (includes speech and swallowing), sensory (includes touch and pain), bowel and bladder, visual, mental and other neurological functional limitations attributed 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: Up to 36 weeks from randomization ]
    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 qualifies the degree of impairment from 0 to 100 (lower 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Official Title  ICMJE A Phase II Study of the Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
Brief Summary

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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Drug: Teriflunomide

    film-coated tablet

    oral administration

    Other Name: HMR1726
  • Drug: Placebo (placebo for teriflunomide)

    film-coated tablet

    oral administration

Study Arms  ICMJE
  • Placebo Comparator: Placebo

    Placebo (for teriflunomide),

    • two tablets once daily for 1 week then,
    • one tablet once daily for 35 weeks.
    Intervention: Drug: Placebo (placebo for teriflunomide)
  • Experimental: Teriflunomide 7 mg

    Teriflunomide 7 mg:

    • two tablets once daily for 1 week then,
    • one tablet once daily for 35 weeks.
    Intervention: Drug: Teriflunomide
  • Experimental: Teriflunomide 14 mg

    Teriflunomide 14 mg:

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

*   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: December 5, 2011)
179
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2003
Actual Primary Completion Date March 2003   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE 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 NCT01487096
Other Study ID Numbers  ICMJE HMR1726D/2001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Study Director Clinical Science & Operation - sanofi-aventis
PRS Account Sanofi
Verification Date October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP