E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 describe efficacy, tolerability and convenience of teriflunomide treatment through the evaluation of PROs |
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E.2.2 | Secondary objectives of the trial |
- To describe disease progression using PRO
- To describe clinical outcomes (ie treated relapses) in teriflunomide treated patients
- To describe the change in cognition in teriflunomide treated patients
- To describe safety of teriflunomide in patients treated (based on adverse event reporting)
- To describe adherence and persistence to teriflunomide treatment
- To describe quality of life, activity and leisure over the period of teriflunomide treatment
- To compare patient determined disease steps (PDDS) (1) and expanded disability status scale (EDSS) (2) in assessing MS disease progression |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with a relapsing form of MS (RMS)
- Having signed written informed consent |
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E.4 | Principal exclusion criteria |
- ACCORDING TO LOCAL LABELING
- 18 years of age
- Current or history of receiving teriflunomide
- Previous treatment with leflunomide within 6 months prior to baseline
- Patients with preexisting acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) greater than 2 times the upper limit of normal (ULN)
- Known history of active tuberculosis (TB) or latent TB infection
- Known history of severe immunodeficiency, acquired immunodeficiency syndrome (AIDS), bone marrow disease, acute or severe active infections
- Women who are pregnant or breast-feeding
- Female patients with a positive pregnancy test at screening or women of child-bearing potential who do not agree to use reliable contraception throughout the course of the study
- Male patients (only when required according to local labeling): unwilling to use reliable contraception during the course of the study
- Additional exclusion criteria applicable for EU countries (in accordance with contraindications of EU SmPC)
* Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia
* Patients with severe active infection until resolution
* Patients with severe renal impairment undergoing dialysis, because insufficient clinical experience is available in this patient group
* Patients with severe hypoproteinaemia, e.g. in nephrotic syndrome
- Hypersensitivity to the active substance or to any of the excipients
- Other additional contraindications per local labeling
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment at 48 weeks (W48/EOT) of global satisfaction with teriflunomide treatment, measured by the Treatment Satisfaction Questionnaire for Medicine (TSQM) version 1.4 score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1 - Change in TSQM version 1.4 from baseline to W4 and to W48/EOT of teriflunomide treatment in patients switching from another DMT
2 - Change in TSQM version 1.4 from W4 to W48/EOT in naïve patients
3 - Disease progression: change from baseline to W48/EOT of teriflunomide treatment, measured by the Patient Determined Disease Steps (PDDS) scale
4 - Disease progression: change from baseline to W24 and to W48/EOT of teriflunomide treatment, measured by the Multiple Sclerosis Performance Scale (MSPS) score (4, 5)
5 - Clinical outcomes: treated relapse, time to first treated relapse
6 - Change in cognition: change from baseline to W48/EOT of teriflunomide treatment as measured by the Symbol Digit Modalities Test (SDMT) score
7 - Occurrence of adverse events (AEs) based on AE reporting at each visit
8 - Adherence (ie, compliance) and persistence (ie, duration of exposure) to teriflunomide treatment over 48 weeks
9 - Quality of life: change from baseline to W48/EOT of teriflunomide treatment, measured by the Multiple Sclerosis International Quality of Life (MusiQoL) score (6) and Stern leisure activity scale (7).
10 - EDSS score at baseline and at W48/EOT |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - Baseline to W4 and W4 to W48
2 - W4 to W48
3 - Baseline to W48
4 - Baseline to W24 and W24 to W48
5 - Over 48 weeks
6 - Baseline to W48
7/8 - Over 48 weeks
9 - Baseline to W48
10 - At baseline and at W48
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
convenience and adherence of teriflunomide treatment |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 119 |
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 |
Canada |
Chile |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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Last Subject Last Visist (LSLV) |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 15 |