E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the tolerability and safety of a 7 mg and a 14 mg dose of teriflunomide administered once daily for 24 weeks, compared with placebo in subjects with multiple sclerosis who are concurrently on a stable dose of glatiramer acetate. |
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E.2.2 | Secondary objectives of the trial |
*Effects of teriflunomide 7 and 14 mg, compared with placebo, in combination with a stable dose of glatiramer acetate on : - total number of gadolinium enhancing lesions per T1-weighted MRI scan over the study period - burden of disease ( defined as total volume of all lesions as measured by T2-weighted MRI scans) - relapse rate (defined as number of annualized relapses per year) and the proportion of subjects who experience objective relapses during the study - subject reported fatigue as measured by the Fatigue Impact Scale (FIS) *Population pharmacokinetic analyses of teriflunomide following 7 mg and 14 mg doses, in combination with a stable dose of glatiramer acetate.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients of both gender aged 18 to 55 years with a diagnosis of multiple sclerosis (as defined by McDonald's criteria) who are ambulatory (Expanded Disability Status Scale [EDSS] of < or = to 5.5). -Stable dose of glatiramer acetate for at least 26 weeks prior to the screening visit -No onset of MS relapse in the preceding 60 days prior to randomization -Clinically stable for 4 weeks prior to randomization -Main informed consent and informed consent for HIV testing form signed |
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E.4 | Principal exclusion criteria |
*disease related: -cancer, lymphoproliferative disease or lymphoïd irradiation -Impaired bone marrow function; significant anemia, leukopenia, or thrombocytopenia -Congenital or acquired severe immunodeficiency, HIV positive subjects, persistent significant or severe infection, tuberculosis -Liver function impairment or persisting elevation of alanine transaminase(ALT) aspartate transferase (AST), or direct bilirubine >1.5 fold the upper limit of normal (ULN) - Persisting elevations of serum amylase or lipase greater to 2-fold the upper limit of normal -chronic pancreatic disease or pancreatitis, chronic active hepatitis -Hypoprotéinemia -Moderate to severe impairment of renal function -Clinically relevant cardiovascular, hypertensive, hepatic, neurological, endocrine, or other systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the subject at risk by participing in the study *Prior or concomitant use or likelihood of requiring treatment during the study period with drugs not permitted - cladribine, mitoxantrone, azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate. - St.John's Wort, phenytoin, warfarin, tolbutamide or cholestyramine; adrenocorticotropic hormone (ACTH) or systemic corticosteroids within 4 weeks prior to randomization (minimum 4 weeks before randomization) -natalizumab TYSABRI -Interferon-beta or cytokine therapy, immunoglobins or any investigational drug in the preceding 24 weeks - Previous treatment with teriflunomide or leflunomide (ARAVA) *Contra-indicating for MRI *Other -Pregnancy, breastfeeding, wishing to parent children -History of drug or alcohol abuse -Mental condition rendering the subject unable to understand the nature, scope, and possible consequence of the study -Subject unlikely to comply with protocol -Subject involved in the conduct of protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety (adverse event reports; physical examination and laboratory evaluation)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 16 |