Primary: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…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary:
- Mean change from Baseline in MS-related fatigue (FSMC) at 12 months in
subjects receiving DMF
Secondary outcome
Secondary:
- 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
Exploratory:
- Relationship of serum biomarker values to fatigue (change in biomarker value)
Background summary
Fatigue is a common symptom of multiple sclerosis (MS), impacting 75% to 95% of
patients and directly contributing to cognitive and physical difficulties. More
than half of patients diagnosed with MS report fatigue as one of their most
disabling symptoms. Commonly used medications for MS have shown limited
improvement in fatigue; hence, a treatment that would alleviate fatigue could
improve the quality of life for individuals with MS. Increased oxidative stress
has been observed in disorders in which fatigue is a prominent symptom,
including chronic fatigue. Nonclinical and initial clinical studies of
Tecfidera (dimethyl fumarate) gastro-resistant hard capsules (hereinafter
referred to as DMF), a novel, oral, disease-modifying therapy developed for
RRMS, suggest that the medication reduces both inflammation and oxidative
stress. Given that such reductions are likely to decrease fatigue, this study
will evaluate the effect of DMF on MS-related fatigue.
This study will investigate in a subset of subjects the impact of DMF treatment
on serum biomarkers associated with endothelial inflammation, nitric oxide
production, and chronic fatigue. Samples may also be used to identify or verify
deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and other biomarkers
associated with disease and response to DMF. The relationship of serum
biomarker levels with MS-related fatigue will also be assessed.
Study objective
Primary:
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.
Secondary:
- 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
Exploratory:
- To assess the association between fatigue and serum biomarkers in a subset of
subjects in Denmark and Finland
Study design
This multicenter study will evaluate MS-related fatigue in up to 320 subjects
with RRMS receiving DMF at approximately 30 study sites across Europe. Subjects
will have up to 6 scheduled clinic visits over a 12-month period.
Completed PRO questionnaires will be collected at various timepoints during the
study. Any changes in fatigue-related medication use will be recorded with
associated doses.
Intervention
The selected dose of DMF for this study is 120 mg twice daily (BID) for the
first 7 days and 240 mg BID thereafter, which is consistent with the European
Union Summary of Product Characteristics (SmPC).
Study burden and risks
The following assessments/evaluations will be used for all subjects:
- Demographics
- Height and weight
- Medical history, including duration of MS, relapse history in the previous 6
months, relapse status during the study, EDSS score, and any previous
treatments for MS
- Alcohol consumption
- Tobacco use
- Concomitant medications and therapies
- All adverse events (AEs) and serious adverse events (SAEs)
- Changes in any fatigue-related medication use
- PRO questionnaires: FSMC, FSS, WPAI-MS, SF-12, 15D HRQoL (in Finland only),
BDI-FS, and ESS
Risks and discomforts:
Serious effects of Tecfidera:
* allergic reactions * these are uncommon and may affect up to 1 in 100 people.
* reddening of the face or body (flushing) * this is a very common (may affect
more than 1 in 10 people) side effect.
Very common side effects of Tecfidera:
These may affect more than 1 in 10 people:
* reddening of the face or body, feeling warm, hot, burning, or itchy (flushing)
* loose stools (diarrhea)
* feeling sick (nausea)
* stomach pain or stomach cramps
Less common risks and side effects are described in the SmPC and ICF.
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Age
Inclusion criteria
1. 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
2. Have a confirmed diagnosis of RRMS and satisfy the therapeutic indication as described in the local label.
3. 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.
4. 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.
5. Age *18 years at the time of informed consent
6. FSMC total score *43 (mild fatigue) at Baseline.
7. As perceived by the Investigator, have the ability to comply with all requirements of the study protocol.
8. 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.
Exclusion criteria
1. Diagnosis of major depression, as identified by the Investigator.
2. Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS.
3. 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.
4. 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.
5. Treatment of MS relapse within 90 days prior to study enrollment.
6. 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.
7. Female subjects who are pregnant or planning to become pregnant during the study period, or who are currently breastfeeding.
8. Impaired hepatic or renal function, as perceived by the Investigator.
9. 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.
10. Treatment within 1 year prior to study enrollment with mitoxantrone or cyclophosphamide.
11. 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.
12. Current enrollment in any other clinical studies.
13. Known to suffer from narcolepsy or another significant sleep disorder.
14. Comorbidity that may have an impact on fatigue.
15. Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001025-53-NL |
| CCMO | NL47368.096.14 |