Investigation of the Effect of Dimethyl Fumarate on T Cells in Patients With Relapsing Remitting Multiple Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02461069
• Date of registration: 27/05/2015
• Prospective Registration: No
• Primary sponsor: University Hospital Muenster
• Public title: Investigation of the Effect of Dimethyl Fumarate on T Cells in Patients With Relapsing Remitting Multiple Sclerosis DIMAT-MS
• Scientific title: A 24-week, Multicenter, Exploratory, Two Arm Study to Assess the Effect of Dimethyl Fumarate on Immune-Modulatory Action on T Cells in Patients With Relapsing Remitting Multiple Sclerosis (DIMAT-MS)
• Date of first enrolment: May 6, 2015
• Target sample size: 67
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02461069
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Germany

Contacts

• Name: Luisa Klotz, Prof. Dr.
• Affiliation: University Hospital Muenster

Key inclusion & exclusion 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.

RRMS patients:

- 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.

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
mofetil.

- MS/H-14. Prior treatment with teriflunomide or leflunomide, unless successful
wash-out, confirmed by plasma concentration of < 0.02 µg/ml.

- MS/H-15. Prior use of any investigational drug in the 6 months preceding screening.

- MS/H-16. Pregnant or breast-feeding women.



Age minimum: 18 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis, Relapsing-Remitting

Intervention(s)

Drug: Dimethyl fumarate

Primary Outcome(s)

Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis. [Time Frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)]

Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects. [Time Frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)]

Secondary Outcome(s)

Mitochondrial energy metabolism of T cells upon dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects. [Time Frame: 0 and 24 weeks after initiation of investigational treatment (week 0)]

Migratory capacity of immune cells (percentage of migrated cells) in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis. [Time Frame: 0 and 24 weeks after initiation of investigational treatment (week 0)]

T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects. [Time Frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)]

Migratory capacity of immune cells (percentage of migrated cells) in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects. [Time Frame: 0 and 24 weeks after initiation of investigational treatment (week 0)]

T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis. [Time Frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)]

Mitochondrial energy metabolism of T cells upon dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis. [Time Frame: 0 and 24 weeks after initiation of investigational treatment (week 0)]

Secondary ID(s)

2014-003481-25

U1111-1164-2476

DIMAT-MS

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Biogen