Trial document




drksid header

  DRKS00008037

Trial Description

start of 1:1-Block title

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)

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

DIMAT-MS

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

This is an exploratory study, which allows analysis of multiple immune parameters derived from peripheral blood
mononuclear cells (PBMCs) from patients with relapsing remitting multiple sclerosis before and during immunemodulatory
treatment with dimethyl fumarate in comparison to PBMCs from healthy subjects.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Investigation of the effect of Dimethyl fumarate on T cells in patients with relapsing remitting Multiple Sclerosis

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00008037
  •   2015/05/22
  •   2015/02/17
  •   yes
  •   Approved
  •   2015-066-f-A, Ethik-Kommission der Ärztekammer Westfalen-Lippe und der med. Fakultät der Westfälischen Wilhelms-Universität Münster
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1164-2476 
  •   2014-003481-25 
  •   EUCTR2014-003481-25-DE  (EUCTR)
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   G35.1 -  message.icd10.coding.redirected.en
  •   Relapsing-remitting multiple sclerose (10063399)
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Patients with relapsing remitting multiple sclerosis will receive dimethyl fumarate from week 0 to week 24. Dimethyl fumarate treatment is initiated by daily administration of 120 mg p.o. in the morning in week 0. At week 1, the dose is increased to 120 mg p.o. twice daily, split into a morning and an evening dose. At week 2, the daily dose is further increased to 240 mg p.o. in the morning and 120 mg p.o. in the evening. Finally at week 3, the dose will be increased to the final daily dose of 240 mg p.o. in the morning and 240 mg p.o. in the evening and maintained to week 24.
  •   Healthy subject without active treatment
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Other
  •   Other
  •   IV
  •   No
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

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.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

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 of the differentiation capacity of helper T cell subpopulations (Th1 and Th17 cells) upon dimethyl fumarate (Tecfidera) treatment in RRMS patients treatment at week 24 compared to baseline.

changes of the differentiation capacity of helper T cells from dimethyl fumarate (Tecfidera)-treated patients compared to T cells from healthy subjects at baseline and week 24.

changes in the migratory capacity of immune cells/PBMCs upon dimethyl fumarate (Tecfidera) treatment in an in-vitro model of the blood-brain-barrier (BBB) 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 on the suppressive capacity of regulatory T cells in respect to suppression of effector T cell responses upon dimethyl fumarate (Tecfidera) treatment at week 24 compared to baseline.

changes on the suppressive capacity of regulatory T cells of dimethyl fumarate (Tecfidera)-treated patients compared to regulatory T cells from healthy subjects in respect to suppression of effector T cell responses 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-barrier (BBB) at week 48 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 week 48.

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Doctor's Practice 
  • Doctor's Practice 
  • Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2015/06/05
  •   75
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   60   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional 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 β-1 or glatiramer acetate and willing to switch to dimethyl fumarate (Tecfidera®).
MS-6. MRI-scan of the brain ≤ 3 months at screening.

end of 1:1-Block inclusion criteria add
start of 1:1-Block 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 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.

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinikum Münster
    • Albert-Schweitzer-Campus 1, Geb. D5
    • 48149  Münster
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Universitätsklinikum Münster Gebäude A1 Neurologie / Ebene 05 West
    • Ms.  PD Dr.  Luisa  Klotz 
    • Albert-Schweitzer-Campus
    • 48149  Münster
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Universitätsklinikum MünsterGebäude A1Neurologie / Ebene 05 West
    • Ms.  PD Dr.  Luisa  Klotz 
    • Albert-Schweitzer-Campus
    • 48149  Münster
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Biogen Idec GmbH
    • Carl-Zeiss-Ring 6
    • 85737  Ismaning
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.