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 | 17.1 |
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 | 17.1 |
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 this study is to determine whether DMF taken over 12 months is effective in reducing MS related fatigue, as measured by mean changes in the Fatigue Scale for Motor and Cognitive Functions (FSMC), in subjects with RRMS. |
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E.2.2 | Secondary objectives of the trial |
To investigate changes from Baseline in FSMC and fatigue severity (Fatigue Severity Scale [FSS]) at 1, 3, 6, 9, and 12 months in subjects receiving DMF
To assess the impact of DMF on patient reported outcomes (PROs), including work productivity (Work Productivity and Activity Impairment-Multiple Sclerosis questionnaire [WPAI-MS]), health-related quality of life (Short Form Health Survey [SF-12] or the 15-dimensional health-related quality of life [15D HRQoL] questionnaire), depression (Beck Depression Inventory-Fast Screen [BDI-FS]), and sleepiness (Epworth Sleepiness Scale [ESS]) at 6 and 12 months in subjects receiving DMF
To examine whether an association exists between fatigue and baseline demographics (e.g., age and sex) and disease characteristics (e.g., disease duration, baseline disease activity, treatment history, expanded disability status scale [EDSS] score, and PROs)
To assess any changes in fatigue-related medication use |
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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 authorization to use protected health information in accordance with national and local subject privacy regulations.
Have a confirmed diagnosis of RRMS and satisfy the therapeutic indication as described in the local label.
Have a stable EDSS (as assessed by the Investigator) and have been on the same (type and dosage) standard of care first line treatment for at least 6 months.
If taking antidepressants, amphetamine, modafinil, or fampridine (Fampyra), subject must be assessed as having been clinically stable for at least 3 months prior to the Baseline Visit.
Age ≥18 years at the time of informed consent.
FSMC total score ≥43 (mild fatigue) at Baseline.
As perceived by the Investigator, have the ability to comply with all requirements of the study protocol.
Female subjects of childbearing potential who are not surgically sterile must practice effective contraception during their participation in the study and be willing and able to continue contraception for 12 weeks after their last dose of study treatment. |
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E.4 | Principal exclusion criteria |
Diagnosis of major depression, as identified by the Investigator.
Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS.
History of malignancy (except for basal cell carcinoma that had been completely excised prior to study entry), severe allergic or anaphylactic reactions or known drug hypersensitivity, abnormal laboratory results indicative of any significant disease, and/or a major disease that would preclude participation in a clinical trial.
History of a relapse within 90 days prior to study enrollment or showing transient symptoms derived from a previous relapse, irrespective of time of symptom onset.
Treatment of MS relapse within 90 days prior to study enrollment.
History of a positive test result for human immunodeficiency virus, hepatitis C virus antibody, or hepatitis B virus (defined as positive for hepatitis B surface antigen or hepatitis B core antibody.
Female subjects who are pregnant or planning to become pregnant during the study period, or who are currently breastfeeding.
Impaired hepatic or renal function, as perceived by the Investigator.
Any prior treatment with DMF (or other fumarate derivative), total lymphoid irradiation, cladribine, fingolimod, T cell or T-cell receptor vaccination, or any therapeutic monoclonal antibody.
Treatment within 1 year prior to study enrollment with mitoxantrone or cyclophosphamide.
Treatment within 6 months prior to study enrollment with cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, intravenous immunoglobulin, plasmapheresis, cytapheresis, or another investigational drug or approved therapy for investigational use.
Current enrollment in any other clinical studies.
Known to suffer from narcolepsy or another significant sleep disorder.
Comorbidity that may have an impact on fatigue.
Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from Baseline in MS-related fatigue (FSMC) at 12 months in subjects receiving DMF. |
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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) |
Mean change from Baseline in fatigue (FSMC and FSS) at 1, 3, 6, 9, and 12 months in subjects receiving DMF
Mean change from Baseline in work productivity, quality of life, depression, and sleepiness at 6 and 12 months in subjects receiving DMF
Change in MS-related fatigue (FSMC) status (improved [> 4.5 increase], stable [within ±4.5], and worsened [> 4.5 decrease])
Correlation of fatigue with baseline demographics and disease characteristics
Proportion of subjects with reduced dose or discontinuation of fatigue related medications at 6 and 12 months |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Mean change from Baseline in fatigue (FSMC and FSS) at 1, 3, 6, 9, and 12 months in subjects receiving DMF
Mean change from Baseline in work productivity, quality of life, depression, and sleepiness at 6 and 12 months in subjects receiving DMF
Change in MS-related fatigue (FSMC) status (improved [> 4.5 increase], stable [within ±4.5], and worsened [> 4.5 decrease])
Correlation of fatigue with baseline demographics and disease characteristics
Proportion of subjects with reduced dose or discontinuation of fatigue related medications at 6 and 12 months |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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, last 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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |