E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 |
Assess the effect of Teriflunomide in comparison to placebo on frequency of Multiple Sclerosis (MS) relapses in patients with relapsing forms of MS who are treated with interferon beta (IFN-β). |
|
E.2.2 | Secondary objectives of the trial |
Assess the effect of Teriflunomide in comparison to placebo when added to interferon beta (IFN-β) on:
. Disease activity as measured by brain Magnetic Resonance Imaging (MRI),
. Disability progression,
. Burden of disease and disease progression as measured by brain MRI.
Evaluate the safety and tolerability of Teriflunomide when added to IFN-β therapy.
Assess the pharmacokinetics of Teriflunomide in use in addition to baseline IFN-β therapy.
Assess associations between variations in genes and clinical outcomes (safety and
efficacy)
Assess other measures of efficacy of teriflunomide in comparison to placebo such as:
− Fatigue
− Health-related quality of life
Assess measures of health economics (hospitalization due to relapse, including the length of stay and any admission to ICU) |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1) Pharmacogenetic substudy to explore the influence of genes on the variability of drug responses and/or drug metabolism to Teriflunomide
2) Immunomarker substudy to evaluate the effects of Teriflunomide in the populations of Lymphocytes and natural killer cells in the peripheral blood
|
|
E.3 | Principal inclusion criteria |
Patient with relapsing forms of multiple sclerosis (MS) treated with Interferon beta (IFN-β) defined by:
- Stable dose of IFN-β for at least 6 months prior to randomization,
and
- Disease activity in the 12 months prior to randomization and after first 3 months of IFN-β treatment (at least one relapse supported by Expanded Disability status Scale (EDSS) or equivalent neurological examination, or, at least one brain or spinal cord Magnetic Resonance Imaging (MRI) with at least one T1 gadolinium enhancing lesion). |
|
E.4 | Principal exclusion criteria |
< 18 years of age or ≥ 56 years of age.
McDonald’s criteria for MS diagnosis not met at time of screening visit.
EDSS score > 5.5 at randomization visit.
A relapse within 30 days prior randomization.
Human Immunodeficiency Virus (HIV) positive patient.
Prior use within 6 months preceding randomization or concomitant use of natalizumab and any other immunosuppresive agents such as azathioprine, cyclophosphamide, cyclosporine, methotrexate, mycophenolate or fingolimod.
Prior use in the 3 months preceding randomization of cytokine therapy (except baseline IFN-β), glatiramer acetate or intravenous immunoglobulins, or concomitant use of these treatments.
Prior use within 2 years preceding randomization or concomitant use of cladribine and mitoxantrone.
Pregnant or breast-feeding women or those who plan to become pregnant during the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Annualized relapse rate (number of confirmed relapses per patient-year) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Average of 2 years (between 1 and 3 years) |
|
E.5.2 | Secondary end point(s) |
1) Number of Gadolinium (Gd)-enhancing T1-lesions as measured by brain MRI
2) Time to disability progression as assessed by Expanded Disability Status Scale (EDSS)
3) Burden of disease
(Change from baseline in the volume of abnormal brain tissue) and other MRI variables
4) Time to first confirmed relapse
5) Proportion of relapse-free patients
6) Subject reported fatigue as assessed by the Fatigue Impact Scale (FIS)
7) Short Form generic health survey [36 items] (SF-36) score
8) Hospitalization due to relapse, including the length of stay and any admission to ICU |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2, 3, 4, 6, 7, 8) Average of 2 years (between 1 and 3 years)
5) 1 year, 2 years, and 3 years |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 248 |
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 | No |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
Colombia |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Greece |
Guatemala |
Hungary |
Italy |
Korea, Republic of |
Lithuania |
Netherlands |
Norway |
Portugal |
Russian Federation |
Slovakia |
Spain |
Sweden |
Tunisia |
Turkey |
United Kingdom |
United States |
|
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
|
Last visit for last patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |