relapsing remitting multiple sclerosis MedDRA version: 19.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Tecfidera® 120mg magensaftresistente Hartkapseln
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: Dimethyl fumarate
CAS Number: 624-49-7
Other descriptive name: DIM
Sponsors
Universitätsklinikum Münster
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Healthy subjects: H-1. Written informed consent must be obtained before any assessment is performed. H-2. Male and female subjects aged 18 - 60 years. H-3. No history of multiple sclerosis or clinically isolated syndrome. H-4. No history of other autoimmune diseases, which has been treated systemically with corticosteroids, immunomodulators or immunosuppressive drugs at any time point. Patients with relapsing remitting multiple sclerosis: MS-1. Written informed consent must be obtained before any assessment is performed. MS-2. Male and female subjects aged 18 - 60 years. MS-3. Patients with RRMS, defined by 2010 revised McDonald criteria. MS-4. Patients with an Expanded Disability Status Scale (EDSS) score of 0-6.0. MS-5. Patients with one of the following treatment status: Naïve to disease modifying (DM) treatment (i.e. no DM treatment for at least 1 month), currently on MS therapy with interferon ß-1 or glatiramer acetate and willing to switch to dimethyl fumarate (Tecfidera®). MS-6. MRI-scan of the brain = 3 months at screening. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 67 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: RRMS patients: MS-1. Known hypersensitivity to dimethyl fumarate or any ingredients of Tecfidera® (microcrystalline cellulose; croscarmellose-sodium; talcum; high dispersion, hydrophobic silicon dioxide; magnesiumstearate (Ph. Eur.); triethylcitrate; methacrylic acid-methacrylate copolymer (1:1) (Ph. Eur.); methacrylic acid-ethylacrylate copolymer (1:1)-dispersion 30% (Ph. Eur.), simeticon, sodiumdodecylsulfate, polysorbate 80, gelantine, titanium oxide (E171), brilliant blue (E133), hydrated Iron(III)-oxide hydroxide (E172), shellac, potassium hydroxide. MS-2. A MS-relapse within 30 days prior to screening. MS-3. Known history of active tuberculosis or active tuberculosis determined by a positive QuantiFERON® TB Gold test (i.e. a negative test result has to be provided at screening unless a negative test result exists from the last 3 months prior to screening). MS-4. Moderate to severe impairment of liver function or persisting elevations > 2 x ULN (confirmed by retest) of serum glutamic pyruvic transaminase/ alanine aminotransferase (SGPT/ALT) or serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST), except patients with confirmed Gilbert´s syndrome (Meulengracht´s disease). MS-5. Moderate to severe impairment of renal function, as shown by serum creatinine > 133 µmol/L (or > 1.5 mg/dL). MS-6. Patients with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia. MS-7. Women of childbearing potential not utilizing highly effective contraception. Both populations: MS/H-1. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. MS/H-2. Subjects unlikely to comply with protocol as determined by investigator, e.g., uncooperative attitude, inability to return for follow-up visits (e.g. major physical disability), and known unlikelihood of completing the study. MS/H-3. Clinically relevant cardiovascular, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the subject at risk by participating in the study. MS/H-4. Subjects with ulcerative colitis or Crohn´s disease. MS/H-5. Subjects with a congenital or acquired severe immunodeficiency, a history of cancer (except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis), lymph proliferative disease, or any subject who has received lymphoid irradiation. MS/H-6. Human immunodeficiency virus (HIV) positive, hepatitis B virus positive or hepatitis C virus positive subjects (i.e. a negative test result has to be provided at screening. In the presence of a negative test result from the last 3 months prior to screening, the test has not to be repeated at screening.). MS/H-7. Acute or chronic infection. MS/H-8. History of drug or alcohol abuse. MS/H-9. Use of adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 4 weeks prior to screening. MS/H-10. Prior or concomitant use of cytokine therapy or intravenous immunoglobulins in the 3 months prior to screening. MS/H-11. Prior use of alemtuzumab or cladribine. MS/H-12. Prior use (within 1 year) of fingolimod (Gilenya®) or natalizumab (Tysabri®). MS/H-13. Prior use (within 2 years) of mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporine, methotrexate or mycophenolate mofet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is an exploratory study design, which allows analysis of multiple immune parameters derived from peripheral blood mononuclear cells (PBMCs) from patients with relapsing remitting multiple sclerosis before and during immune-modulatory treatment with dimethyl fumarate (Tecfidera) in comparison to PBMCs from healthy subjects.;Secondary Objective: Not applicable;Primary end point(s): changes in lymphocyte subpopulations upon dimethyl fumarate (Tecfidera)-treatment in RRMS patients at week 8, 16 and 24 compared to baseline. changes in lymphocyte subpopulations of dimethyl fumarate (Tecfidera)-treated RRMS patients compared to healthy subjects at week 0, 8, 16 and 24. ;Timepoint(s) of evaluation of this end point: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): changes in T cell effector functions, in terms of cytokine production of CD4+ and CD8+ T cells derived of PBMC of dimethyl fumarate (Tecfidera)-treated patients at weeks 8, 16 and 24 as compared to baseline. changes in T cell effector functions, in terms of cytokine production of CD4+ and CD8+ T cells derived of PBMC of dimethyl fumarate (Tecfidera)-treated patients compared to PBMCs of healthy subjects at week 0, 8, 16 and 24. changes in the migratory capacity of immune cells/PBMCs upon dimethyl fumarate (Tecfidera) treatment at week 24 compared to baseline. changes in the migratory capacity of immune cells/PBMCs from dimethyl fumarate (Tecfidera)-treated patients compared to immune cells/PBMCs from healthy subjects in an in-vitro model of the blood-brain-barrier (BBB) at baseline and weeks 24. changes in mitochondrial energy metabolism (i.e. oxidative phosphorylation) of T cells upon dimethyl fumarate (Tecfidera®) treatment at week 24 compared to baseline. changes in mitochondrial energy metabolism (i.e. oxidative phosphorylation) of T cells from dimethyl fumarate (Tecfidera®)-treated patients with T cells from healthy subjects at baseline and week 24. changes in lymphocyte subpopulations upon dimethyl fumarate (Tecfidera) treatment in RRMS patients at week 48 compared to baseline. changes in lymphocyte subpopulations of dimethyl fumarate (Tecfidera)-treated RRMS patients compared to healthy subjects at baseline and week 48. changes in the T cell effector functions of CD4+ and CD8+ T cells derived of PBMC of dimethyl fumarate (Tecfidera)-treated patients at week 48 compared to baseline. changes in the T cell effector functions of CD4+ and CD8+ T cells derived of PBMC of dimethyl fumarate (Tecfidera)-treated patients compared to PBMCs of healthy subjects at baseline and week 48. changes in the migratory capacity of immune cells/PBMCs upon dimethyl fumarate (Tecfidera) treatment in an in-vitro model of the blood-brain-bar | — |
Countries
Germany
Contacts
Public ContactKlinik für Allgemeine Neurologie
Universitätsklinikum Münster
Outcome results
None listed