E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-Remitting Multiple Sclerosis |
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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 | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 | 10063399 |
E.1.2 | Term | Relapsing-remitting 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 |
The primary objective of the study is to estimate the annualized relapse rate (ARR) in subjects with RRMS who are treated with DMF over a 12-month period.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study in this population are to assess the impact of DMF over a 12 month period on patient-reported HRQoL outcomes, additional clinical effectiveness outcomes, and health economics-related outcomes, and to characterize patient-reported adherence to DMF. |
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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 |
Biomarker Sub-Study. Subjects who consent to participate will provide blood samples that will be used to identify or verify deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and serum markers associated with disease and response to DMF. |
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E.3 | Principal inclusion criteria |
Have the ability to understand the purpose and risks of the study and provide signed and dated informed consent and any authorizations required by local law in accordance with national and local subject privacy regulations.
Have a diagnosis of RRMS and satisfy the approved therapeutic indication for DMF (per the local DMF product information).
Must be naïve to DMF, Fumaderm®, and other compounded fumarates, and to MS therapies that are primarily prescribed second-line (e.g., natalizumab, fingolimod) and to alemtuzumab.
Are >18 years old
Have a recent (i.e., within the previous 6 months) complete blood count (CBC) that does not preclude the subject’s participation in the study, in the judgment of the Investigator. |
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E.4 | Principal exclusion criteria |
Are unwilling or unable to comply with study requirements, or are deemed unsuitable for study participation as determined by the Investigator.
Have major comorbid conditions that preclude participation in the study, as determined by the Investigator.
Are pregnant, unless DMF is clearly needed and the potential benefit of DMF to the subjects justifies the potential risk to the fetus, in the judgment of the Investigator (in all countries except Austria). In Austria, pregnant subjects are excluded from participation in the study.
Are women of childbearing potential and are not using appropriate contraception (per the local DMF product information) as determined by the Investigator.
Women who are breastfeeding may be excluded (per the local DMF product information) at the discretion of the Investigator.
Have previously received or are receiving treatment with MS therapies primarily used second-line (e.g., natalizumab, fingolimod) or alemtuzumab, or are currently receiving and planning to continue on other disease-modifying therapies for RRMS, including but not limited to interferon β, glatiramer acetate, teriflunomide, or laquinimod.
Are hypersensitive to the active ingredient in the DMF drug product (i.e., DMF) or to any of the excipients listed in the local DMF product information.
Current enrollment in any clinical trial or Biogen Idec-sponsored study except for the DMF Pregnancy Exposure Registry or other studies that, according to the study Medical Director, do not conflict with this study (e.g., health economics studies or local registries). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Annualized Relapse Rate (ARR) |
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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) |
Change from baseline to Month 12 in:
- Multiple Sclerosis Impact Scale (MSIS 29) score
- Modified Fatigue Impact Scale-5 Item (MFIS-5) score
- Treatment Satisfaction Questionnaire for Medication (TSQM) score
- EQ-5D 5 level version (EQ-5D-5L) index and EQ Visual Analog Scale (EQ VAS) score
- Patient-Reported Indices for Multiple Sclerosis-Activity Limitations (PRIMUS-Activity Limitations) score
- Work Productivity and Activity Impairment-Multiple Sclerosis version (WPAI-MS) score
- Beck Depression Inventory—Fast Screen (BDI-Fast Screen) score
Proportion of subjects with confirmed (24-week) Expanded Disability Status Scale (EDSS) progression at Month 12
The ARR at Baseline (i.e., over the 12 months prior to baseline) and at Month 6
The proportion of subjects relapsed at Month 12
Number and proportion of subjects who are hospitalized/have emergency room visits due to MS relapses or have relapses requiring intravenous (IV) steroid treatment during the study, or who make visits to neurologists/other specialists due to MS
Proportion of subjects who report taking the prescribed DMF dose, overall percent adherence, and reasons for not taking full dose |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 months for secondary endpoints except for:
The ARR at Baseline (i.e., over the 12 months prior to baseline) and at Month 6 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | 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) | 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 | Yes |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 109 |
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 |
Belgium |
Canada |
France |
Italy |
Austria |
Portugal |
Slovakia |
Czech Republic |
Hungary |
Spain |
Slovenia |
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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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LVLS: The end of study is last subject’s last visit (Month 12 End of Treatment/Early Discontinuation Visit) for final collection of data for the primary outcome. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
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 |