Clinical Trials Register

Summary
EudraCT Number:	2014-003481-25
Sponsor's Protocol Code Number:	DIMAT-MS
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-02-17
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2014-003481-25

A.3

Full title of the trial

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

Eine 24-wöchige, multizentrische, explorative, 2-armige Studie zur Beurteilung der Wirkung von Dimethylfumarat auf den immunmodulatorischen Einfluss von T-Zellen bei Patienten mit schubförmig remittierender Multiplen Sklerose

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Untersuchung der Wirkung von Dimethylfumarat auf T-Zellen von Patienten mit schubförmig remittierender Multiplen Sklerose

A.3.2

Name or abbreviated title of the trial where available

DIMAT-MS

A.4.1

Sponsor's protocol code number

DIMAT-MS

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1164-2476

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Universitätsklinikum Münster
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Biogen Idec GmbH, Ismaning
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universitätsklinikum Münster
B.5.2	Functional name of contact point	Klinik für Allgemeine Neurologie
B.5.3	Address:
B.5.3.1	Street Address	Albert-Schweitzer-Campus 1, Gebäude A1
B.5.3.2	Town/ city	Münster
B.5.3.3	Post code	48149
B.5.3.4	Country	Germany
B.5.6	E-mail	Luisa.Klotz@ukmuenster.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tecfidera® 120mg magensaftresistente Hartkapseln
D.2.1.1.2	Name of the Marketing Authorisation holder	Biogen Idec Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Gastro-resistant capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dimethyl fumarate
D.3.9.1	CAS number	624-49-7
D.3.9.3	Other descriptive name	DIMETHYL FUMARATE
D.3.9.4	EV Substance Code	SUB13608MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tecfidera® 240mg magensaftresistente Hartkapseln
D.2.1.1.2	Name of the Marketing Authorisation holder	Biogen Idec Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Gastro-resistant capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dimethyl fumarate
D.3.9.1	CAS number	624-49-7
D.3.9.3	Other descriptive name	DIMETHYL FUMARATE
D.3.9.4	EV Substance Code	SUB13608MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	240
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

relapsing remitting multiple sclerosis

schubförmig remittierende multiple Sklerose

E.1.1.1

Medical condition in easily understood language

relapsing remitting multiple sclerosis

schubförmig remittierende multiple Sklerose

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	PT
E.1.2	Classification code	10063399
E.1.2	Term	Relapsing-remitting multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

Mit Hilfe eines explorativen Studiendesigns werden multiple Immunparameter von mononukleären Zellen des peripheren Blutes (PBMCs) von Patienten mit schubförmig remittierender multiplen Sklerose mit PBMCs von gesunden Probanden vor und während der immunmodulatorischen Behandlung mit Dimethylfumarat (Tecfidera) verglichen

E.2.2

Secondary objectives of the trial

Not applicable

Nicht zutreffend

E.2.3

Trial contains a sub-study

E.3

Principal 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.

Gesunde Probanden:
H-1. Unterzeichnete Einwilligungserklärung.
H-2. Männer und Frauen im Alter von 18 - 60 Jahren.
H-3. Keine Vorgeschichte von Multipler Sklerose oder klinisch isoliertem Syndrom.
H-4. Keine Vorgeschichte von Autoimmunerkrankungen, welche systemisch mit Corticosteroiden, immunmodulatorischen oder immunsupprimierenden Medikamenten behandelt wurden.

Patienten mit schubförmig remittierender multipler Sklerose (RRMS):
MS-1. Unterzeichnete Einwilligungserklärung.
MS-2. Männer und Frauen im Alter von 18 - 60 Jahren.
MS-3. Patienten mit RRMS, bestimmt mit den McDonald-Kriterien (Revision 2005).
MS-4. Patienten mit einem Expanded Disability Status Scale (EDSS)-Score von 0-6.0.
MS-5. Die Patienten müssen medikamentennaiv gegenüber einer krankheitsmodifizierenden Behandlung sein (d.h. keine krankheitsmodifizierende Behandlung für mindestens einen Monat) oder erhalten gegenwärtig eine MS-Therapie mit Interferon β-1 oder Glatirameracetat und der Patient willigt ein auf Dimethylfumarat (Tecfidera®) zu wechseln.
MS-6. MRT-Scan vom Gehirn, der zum Zeitpunkt des Screenings max. 3 Monate alt ist.

E.4

Principal 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.

RRMS patients:
MS-1. Bekannte Überempfindlichkeit gegenüber Dimethylfumarat oder einem Hilfsstoff von Tecfidera® (Mikrokristalline Cellulose,Croscarmellose-Natrium, Talkum, Hochdisperses, hydrophobes Siliciumdioxid, Magnesiumstearat (Ph. Eur.), Triethylcitrat, Methacrylsäure-Methylmethacrylat- Copolymer (1 : 1) (Ph. Eur.), Methacrylsäure-Ethylacrylat-Copolymer-
(1 : 1)-Dispersion 30% (Ph. Eur.), Simeticon, Natriumdodecylsulfat, Polysorbat 80, Gelatine, Titandioxid (E 171), Brillantblau FCF (E 133), Eisen(III)-hydroxid-oxid (E 172), Schellack, Kaliumhydroxid, Eisen(II,III)-oxid (E 172).
MS-2. Einen MS-Schub in den letzten 30 Tagen vor dem Screening.
MS-3. Keine bekannte Vorgeschichte einer aktiven Tuberkulose oder eine aktive Tuberkulose, die mit Hilfe des QuantiFERON® TB Gold-Tests festgestellt wird, d.h. es muss zum Zeitpunkt des Screenings ein negatives Ergebnis vorliegen, sofern kein negativer Test in den letzten drei Monaten vor dem Screening durchgeführt wurde.
MS-4. Mittelschwere oder schwere Beeinträchtigung der Leberfunktion oder anhaltend hohe Leberwerte > 2 x ULN (bestätigt durch einen zweiten Test) Serum Glutamat-Pyruvat-Transaminase/ Alanin- Aminotransferase (SGPT/ALT) oder Serum Glutamat-Oxalacetat- Transaminase/ Aspartat-Aminotransferase (SGOT/AST), mit Ausnahme von Patienten mit einem bestätigten Gilbert-Meulengracht-Syndrom (Morbus Meulengracht).
MS-5. Mittelschwere oder schwere Beeinträchtigung der Nierenfunktion, Serumkreatinin > 133 μmol/L (or > 1.5 mg/dL).
MS-6. Patienten mit signifikant beeinträchtigter Knochenmarksfunktion oder signifikanter Anämie, Leukopenie, Neutropenie oder Thrombozytopenie.
MS-7. Gebärfähige Frauen, die keine hocheffektive Schwangerschaftsverhütung verwenden.

Beide Populationen:
MS/H-1. Der mentale Zustand des Patienten/Probanden hindert ihn, das Wesen, den Umfang und die möglichen Konsequenzen dieser Studie zu erfassen.
MS/H-2. Patienten/Probanden, die nach Einschätzung des Prüfarztes nicht in der Lage sind, das Protokoll einzuhalten. Bspw. unkooperatives Verhalten, Unfähigkeit, die Folgevisiten zu besuchen (bspw. schwere Körperbehinderung), es liegt eine hohe Wahrscheinlichkeit vor, dass die Studie nicht beendet wird.
MS/H-3. Klinisch relevante kardiovaskuläre, neurologische, endokrinologische oder andere schwere systemische Erkrankungen, die die Umsetzung des Protokolls oder die Interpretation der Studienergebnisse schwierig machen oder den Patienten in Gefahr bringen.
MS/H-4. Patienten/Probanden mit Colitis ulcerosa oder Morbus Crohn.
MS/H-5. Patienten/Probanden mit einer angeborenen oder erworbenen schweren Immunschwäche, einer aktuellen oder vergangenen Krebserkrankung (außer Basalzell- oder Plattenepithelzellkarzinome, welche chirurgisch entfernt wurden sowie keine Anzeichen der Metastasierung aufweisen), einer lymphoproliferativen Erkrankung, oder jeder Patient/Proband, der eine Bestrahlung der Lymphregionen erhalten hat.
MS/H-6. Humanes Immundefizienz-Virus (HIV)-positive, Hepatitis B-Virus- positive oder Hepatitis C-Virus-positive Patienten/Probanden. Sollte ein negatives Testergebnis aus den letzten drei Monaten vor dem Screening vorliegen, so muss der Test nicht wiederholt werden.
MS/H-7. Akute oder chronische Infektionen.
MS/H-8. Drogen- oder Alkoholmissbrauch in der Krankengeschichte.
MS/H-9. Anwendung von adrenokorticotropen Hormonen (ACTH) oder systemischen Kortikosteroiden für 4 Wochen im Vorfeld des Screenings.
MS/H-10. Vorherige oder begleitende Durchführung einer Zytokin-Therapie oder der ein Einsatz intravenöser Immunglobuline innerhalb 3 Monate vor dem Screening.
MS/H-11. Vorherige Therapie mit Alemtuzumab oder Cladribin.
MS/H-12. Vorherige Therapie (innerhalb eines Jahres) mit Fingolimod (Gilenya®) oder Natalizumab (Tysabri®).
MS/H-13. Vorherige Therapie (innerhalb 2 Jahren) mit Mitoxantron oder anderen immunsupprimierenden Medikamenten wie Azathioprin, Cyclophosphamid, Cyclosporin, Methotrexat oder Mycophenolate mofetil.
MS/H-14. Vorherige Therapie mit Teriflunomid oder Leflunomid. Es sei denn, eine Auswaschphase wurde erfolgreich durchgeführt und durch eine Plasmakonzentration von < 0.02 µg/ml bestätigt.
MS/H-15. Einnahme von Prüfmedikamenten in den letzten 6 Monaten vor dem Screening.
MS/H-16. Schwangere oder stillende Frauen.

E.5 End points

E.5.1

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.

Änderung der Lymphozytensubpopulation an Woche 8, 16 und 24 von RRMS-Patienten unter Behandlung mit Dimethylfumarat (Tecfidera) im Vergleich zu Woche 0.

Änderung der Lymphozytensubpopulation an Woche 0, 8, 16 und 24 von Dimethylfumarat (Tecfidera) behandelten RRMS-Patienten im Vergleich zu gesunden Probanden.

E.5.1.1

Timepoint(s) of evaluation of this end point

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

0, 8, 16 und 24 Wochen nach Beginn der Prüfbehandlung (Woche 0).

E.5.2

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-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.

Änderung der Effektorfunktion von T-Zellen, was die Zytokinproduktion von CD4+ und CD8+ T-Zellen betrifft, an Woche 8, 16 und 24 von RRMS-Patienten unter Behandlung mit Dimethylfumarat (Tecfidera) im Vergleich zu Woche 0.

Änderung der Effektorfunktion von T-Zellen, was die Zytokinproduktion von CD4+ und CD8+ T-Zellen betrifft, an Woche 0, 8, 16 und 24 von Dimethylfumarat (Tecfidera) behandelten RRMS-Patienten im Vergleich zu gesunden Probanden.

Änderung der Kapazität zur Migration von Immunzellen/PBMCs an Woche 24 von RRMS-Patienten unter Behandlung mit Dimethylfumarat (Tecfidera) im Vergleich zu Woche 0.

Änderung der Kapazität zur Migration von Immunzellen/PBMCs an Woche 0 und 24 von Dimethylfumarat (Tecfidera) behandelten RRMS-Patienten im Vergleich zu gesunden Probanden.

Änderung des mitochondrialen Energiemetabolismus von T-Zellen an Woche 24 von RRMS-Patienten unter Behandlung mit Dimethylfumarat (Tecfidera) im Vergleich zu Woche 0.

Änderung des mitochondrialen Energiemetabolismus von T-Zellen an Woche 0 und 24 von Dimethylfumarat (Tecfidera) behandelten RRMS-Patienten im Vergleich zu gesunden Probanden.

Änderung in der Lymphozytensubpopulation an Woche 48 von RRMS-Patienten unter Behandlung mit Dimethylfumarat (Tecfidera) im Vergleich zu Woche 0.

Änderung der Lymphozytensubpopulation an Woche 0 und 48 von Dimethylfumarat (Tecfidera) behandelten RRMS-Patienten im Vergleich zu gesunden Probanden.

Änderung der T-Zell-Effektorfunktion von CD4+ and CD8+ T-Zellen an Woche 48 von RRMS-Patienten unter Behandlung mit Dimethylfumarat (Tecfidera) im Vergleich zu Woche 0.

Änderung der T-Zell-Effektorfunktion von CD4+ and CD8+ T-Zellen an Woche 48 von Dimethylfumarat (Tecfidera) behandelten RRMS-Patienten im Vergleich zu gesunden Probanden.

Änderung der Kapazität zur Migration von Immunzellen/PBMCs an Woche 48 von RRMS-Patienten unter Behandlung mit Dimethylfumarat (Tecfidera) im Vergleich zu Woche 0.

Änderung der Kapazität zur Migration von Immunzellen/PBMCs an Woche 0 und 48 von RRMS-Patienten unter Behandlung mit Dimethylfumarat (Tecfidera) im Vergleich zu gesunden Probanden.

E.5.2.1

Timepoint(s) of evaluation of this end point

0, 8, 16, 24 and 48 weeks after initiation of investigational treatment (week 0).

0, 8, 16, 24 und 48 Wochen nach Beginn der Prüfbehandlung (Woche 0).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Gesunde Probanden ohne aktive Behandlung

Healthy subject without active treatment

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of trial will be at database lock, which will be accomplished at the latest 12 months after the last visit of the last subject (LVLS), regarding the time-consuming immunological analysis.

Das Studienende ist bei Datenbankschluss, der spätestens 12 Monate nach dem letzten Besuch des letzten Patienten stattfindet, da die immunologischen Analysen sehr zeitaufwendig sind.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2015-02-17.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients may choose to receive post-study care from the study site or from a resident neurologist of their choice. As Tecfidera is already approved for patients with relapsing remitting multiple sclerosis, an ongoing therapy with Tecfidera after end of the study is possible.

Nach Wahl des Patienten erfolgt die medizinische Versorgung nach Studienende am Studienzentrum oder bei einem niedergelassenen Neurologen. Da Tecfidera für die Behandlung von Patienten mit schubförmig remittierender Multiplen Sklerose zugelassen ist, kann eine Weiterführung der Therapie mit Tecfidera nach Studienende erfolgen.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-03-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-05-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-05-07

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