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

NCT02461069 | Completed Phase 4

• 3 other identifiers: DIMAT-MS2014-003481-25U1111-1164-2476
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 6

Brief Summary

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 immune-modulatory treatment with dimethyl fumarate in comparison to PBMCs from healthy subjects.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

dimethyl fumarate

Outcome Measures

Primary Outcomes (2)

• Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.

  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.

  0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)

Secondary Outcomes (6)

• T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.

  0, 8, 16 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.

  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.

  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 and untreated healthy subjects.

  0 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.

  0 and 24 weeks after initiation of investigational treatment (week 0)

Study Arms (2)

Dimethyl fumarate treatment arm (A)

ACTIVE COMPARATOR

All patients will receive dimethyl fumarate (Tecfidera®) according to national recommendations (Krankheitsbezogenes Kompetenznetz Multiple Sklerose, KKNMS) from week 0 to week 24 (EOS-1) in the core study.

Drug: Dimethyl fumarate

Healthy subject arm (B)

NO INTERVENTION

Healthy subjects will not receive any treatment for RRMS during the study.

Interventions

Dimethyl fumarate DRUG

Dimethyl fumarate (Tecfidera®) treatment is initiated by daily administration of 120 mg Tecfidera® p.o. in the morning in week 0. At week 1, the dose is increased to 120 mg Tecfidera® p.o. twice daily, split into a morning and an evening dose. At week 2, the daily dose is further increased to 240 mg Tecfidera® p.o. in the morning and 120 mg Tecfidera® p.o. in the evening. Finally at week 3, the dose will be increased to the final daily dose of 240 mg Tecfidera® p.o. in the morning and 240 mg Tecfidera® p.o. in the evening and maintained throughout the study.

Also known as: Tecfidera®

Dimethyl fumarate treatment arm (A)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.).

Sponsors & Collaborators

• University Hospital Muenster: lead
• Biogen: collaborator

Study Sites (6)

Neurologisches Studienzentrum Dr. Schmidt/Dr. Neudecker/ Dr. Viehbahn/Dr. Kronenberger

Bonn, 53111, Germany

Location

Neurologische Gemeinschaftspraxis im Bienenkorbhaus

Frankfurt am Main, 60313, Germany

Location

Neurologische Univ.-Klinik

Heidelberg, 69120, Germany

Location

Klinik und Poliklinik für Neurologie, Universitätsklinikum Mainz

Mainz, 55131, Germany

Location

University Hospital Muenster, Department of Neurology

Münster, 48149, Germany

Location

MVZ-Neurologie Klinikum Osnabrück GmbH

Osnabrück, 49076, Germany

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Luisa Klotz, Prof. Dr.

  University Hospital Muenster

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: June 3, 2015
• Study Start: May 6, 2015
• Primary Completion: January 24, 2018
• Study Completion: May 7, 2018
• Last Updated: October 11, 2018

Record last verified: 2018-10

Locations

DE (6)