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    Summary
    EudraCT Number:2012-000055-13
    Sponsor's Protocol Code Number:M41008-1102
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-09-11
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedAustria - BASG
    A.2EudraCT number2012-000055-13
    A.3Full title of the trial
    A multi-center, randomized, double-blind, three-arm, 16 week, adaptive phase III clinical study to investigate the efficacy and safety of LAS41008 vs LASW1835 and vs Placebo in patients with moderate to severe plaque psoriasis
    Eine multizentrische, randomisierte, doppel-blinde, dreiarmige, adaptive klinische Studie der Phase III über 16 Wochen zur Untersuchung der Wirksamkeit und Sicherheit von LAS41008 versus LASW1835 und versus Placebo bei Patienten mit mittelschwerer bis schwerer chronischer Plaque-Psoriasis.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A multi-center, randomized, clinical trial to compare the efficacy and safety of a new drug with Fumaderm in patients with moderate to severe plaque psoriasis
    Eine multizentrische, randomisierte klinische Studie, um die Wirksamkeit und Sicherheit eines neuen Medikamentes mit Fumaderm in Patienten mit mäßiger bis schwerer Schuppenflechte zu vergleichen.
    A.3.2Name or abbreviated title of the trial where available
    Efficacy and safety of LAS41008 in patients with moderate to severe plaque psoriasis
    Wirksamkeit und Sicherheit von LAS41008 in Patienten mit mäßiger bis schwerer Schuppenflechte
    A.4.1Sponsor's protocol code numberM41008-1102
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAlmirall S.A.
    B.1.3.4CountrySpain
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAlmirall S.A.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAlmirall S.A.
    B.5.2Functional name of contact pointDr. med. Veronica Tebbs
    B.5.3 Address:
    B.5.3.1Street AddressRda. General Mitre 151
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08022
    B.5.3.4CountrySpain
    B.5.4Telephone number++494072704242
    B.5.5Fax number++494072704295
    B.5.6E-mailveronica.tebbs@almirall.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code LAS41008 30 mg
    D.3.4Pharmaceutical form Gastro-resistant tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDimethyl (E)-butenedioate
    D.3.9.1CAS number 624-49-7
    D.3.9.3Other descriptive nameDIMETHYL FUMARATE
    D.3.9.4EV Substance CodeSUB13608MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code LAS41008 120 mg
    D.3.4Pharmaceutical form Gastro-resistant tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDimethyl (E)-butenedioate
    D.3.9.1CAS number 624-49-7
    D.3.9.3Other descriptive nameDIMETHYL FUMARATE
    D.3.9.4EV Substance CodeSUB13608MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Fumaderm initial
    D.2.1.1.2Name of the Marketing Authorisation holderBiogen Idec GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameFumaderm initial
    D.3.4Pharmaceutical form Gastro-resistant tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDimethyl (E)-butenedioate
    D.3.9.1CAS number 624-49-7
    D.3.9.3Other descriptive nameDIMETHYL FUMARATE
    D.3.9.4EV Substance CodeSUB13608MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEthyl hydrogen fumarate, calcium salt
    D.3.9.3Other descriptive nameCalcium monoethylfumarate
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number67
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEthyl hydrogen fumarate, magnesium salt
    D.3.9.3Other descriptive nameMagnesium monoethylfumarate
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEthyl hydrogen fumarate, zinc salt
    D.3.9.3Other descriptive nameZinc monoethylfumarate
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Fumaderm
    D.2.1.1.2Name of the Marketing Authorisation holderBiogen Idec GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameFumaderm
    D.3.4Pharmaceutical form Gastro-resistant tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDimethyl (E)-butenedioate
    D.3.9.1CAS number 624-49-7
    D.3.9.3Other descriptive nameDIMETHYL FUMARATE
    D.3.9.4EV Substance CodeSUB13608MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEthyl hydrogen fumarate, calcium salt
    D.3.9.3Other descriptive nameCalcium monoethylfumarate
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number87
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEthyl hydrogen fumarate, magnesium salt
    D.3.9.3Other descriptive nameMagnesium monoethylfumarate
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEthyl hydrogen fumarate, zinc salt
    D.3.9.3Other descriptive nameZinc monoethylfumarate
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboGastro-resistant tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboGastro-resistant tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboGastro-resistant tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    moderate to severe chronic plaque psoriasis
    mittelschwere bis schwere Formen der Psoriasis vulgaris
    E.1.1.1Medical condition in easily understood language
    moderate to severe chronic plaque psoriasis
    mittelschwere bis schwere Formen der Psoriasis vulgaris
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10071117
    E.1.2Term Plaque psoriasis
    E.1.2System Organ Class 100000004858
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10050576
    E.1.2Term Psoriasis vulgaris
    E.1.2System Organ Class 100000004858
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objectives of the study are:
    - Superiority of LAS41008 versus placebo based on the proportion of subjects achieving PASI 75 at week 16 (a 75% reduction in the Psoriasis Area and Severity Index, PASI, compared to baseline.
    - Superiority of LAS41008 versus placebo based on the proportion of subjects achieving a score of “clear” or ”almost clear” in the Physician’s Global Assessment (PGA) after 16 weeks of treatment.
    - Non-inferiority of LAS41008 compared to LASW1835 (internal code for Fumaderm®) regarding PASI 75 after 16 weeks of treatment.
    Die Primärziele der Studie sind:
    • Überlegenheit von LAS41008 versus Placebo basierend auf dem Anteil der Patienten, die einen PASI 75 (eine Reduktion des ‘Psoriasis Area and Severity‘-Index, PASI, um 75% im Vergleich zu Baseline) in Woche 16 erreichen.
    • Überlegenheit von LAS41008 versus Placebo basierend auf dem Anteil der Patienten, die gemäß ‘Physician’s Global Assessment’ (PGA) eine Beurteilung von ‚abgeklungen‘ (‘clear’) oder ‚fast abgeklungen‘ (‚almost clear‘) nach einer Behandlung über 16 Wochen erreicht haben.
    • Nicht-Unterlegenheit von LAS41008 im Vergleich zu LASW1835 (interner Code für Fumaderm®) hinsichtlich PASI 75 nach einer Behandlung über 16 Wochen.
    E.2.2Secondary objectives of the trial
    Secondary Objectives:
    - Superiority of LAS41008 versus placebo based on changes on PASI, PGA after 3 and 8 weeks and BSA after 3, 8 and 16 weeks.
    - Non-inferiority of LAS41008 compared to Fumaderm® regarding PASI 75 after 3 and 8 weeks of treatment.
    - Assessment of the safety of LAS41008 compared to Fumaderm® and Placebo for both treatment periods (30/120mg dimethyl fumarate).
    - Assessment of the safety of LAS41008 compared to Fumaderm® when administered concomitantly with medicines known to have potential nephrotoxic effects, e.g. angiotensin-converting enzyme, angiotensin II inhibitors and statins.
    a. Überlegenheit von LAS41008 versus Placebo basierend auf den Änderungen von PASI und PGA nach 3 und 8 Wochen, und BSA nach 3, 8 und 16 Wochen.
    b. Nicht-Unterlegenheit von LAS41008 im Vergleich zu Fumaderm® hinsichtlich PASI 75 nach einer Behandlung über 3 und 8 Wochen.
    c. Beurteilung der Sicherheit von LAS41008 im Vergleich zu Fumaderm® und Placebo in beiden Behandlungsperioden (30/120mg Dimethylfumarat).
    d. Beurteilung der Sicherheit von LAS41008 im Vergleich zu Fumaderm® wenn gleichzeitig mit Medikationen eingenommen wird, welche wissentlich mögliche nephrotoxische Effekte haben können, z.B. angiotensin-converting enzyme, angiotensin II Hemmer und Statine.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Signed and personally dated written informed consent
    - Male / female
    - Aged 18 years or older
    - With a diagnosis of chronic plaque psoriasis for at least 12 months before enrollment in the study
    - With the severity of psoriasis defined as moderate to severe, as reflected in meeting all the following criteria:
    PASI > 10
    BSA (body surface area) > 10 %
    PGA moderate to severe
    - With general good health, or a stable medical condition not considered likely to interfere with the conduct of the clinical study, as determined by the investigator based upon results of medical history, laboratory results and physical examination
    - Prior therapy with systemic drugs for psoriasis that was discontinued e.g. due to an adverse event or insufficient effect, or naïve to systemic treatment but identified as a candidate for systemic treatment.
    - With a complete record of at least 12 months of other previous topical and systemic treatments, if any
    - Adhering to the wash-out periods as stated in the protocol
    - For females of child-bearing potential: a negative serum pregnancy test at screening and willing to use highly effective methods of birth control during the study period and for 60 days after the last dose of investigational product. Additionally they must agree to have pregnancy tests while on study medication. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner. Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.
    - Males (except vasectomized males) must agree to use barrier contraception while on study medication
    - Willing to keep sun exposure reasonably constant and not to use tanning booths or other UV light sources for the duration of the trial
    Einschlusskriterien:
    (1) Unterzeichnete und persönlich datierte schriftliche Einwilligungserklärung
    (2) Männlich / weiblich
    (3) Im Alter von 18 Jahren oder älter
    (4) Mit einer Diagnose einer chronischen Plaque-Psoriasis seit mindestens 12 Monaten vor Aufnahme in die Studie
    (5) Mit einem Schweregrad der Psoriasis definiert als mittelschwer bis schwer, nachgewiesen indem alle der folgenden Kriterien zutreffen:
    o PASI > 10
    o BSA (body surface area) > 10 %
    o PGA mittelschwer bis schwer
    (6) Eine allgemein gute Gesundheit oder ein stabiler medizinischer Gesundheitszustand, der, basierend auf der Beurteilung des Prüfarztes anhand Krankengeschichte, Laborergebnissen und Ergebnissen der medizinischen Untersuchung, voraussichtlich nicht die Durchführung der klinischen Studie beeinflusst.
    (7) Vorangegangene Therapie mit systemischen Medikamenten für die Psoriasis die beispielsweise wegen einem unerwünschtem Ereignis oder unausreichender Wirkung abgesetzt wurde oder naïv bezüglich systemischer Behandlung aber identifiziert als Kandidat für systemische Therapie.
    (8) Mit einer vollständigen Akte über ggf. andere vorangegangene topische und systemische Behandlungen innerhalb der letzten 12 Monate
    (9) Einhaltung der folgenden Auswaschperioden
    - Topische Behandlung: Kortikosteroide, Vitamin A Analoga,
    Vitamin D Analoga, Anthracenederivate, Teer, Salicylsäurepräparate: 2 Wochen
    - Systemische Behandlung:
    --Biologika mit antipsoriatischer Aktivität: 3 Monate
    --Konventionelle systemische antipsoriatische Medikamente und Phototherapie: 1 Monat
    - Immunosuppressiva:
    - Cytostatics
    (falls diese nicht in einer der oben genannten Behandlungen enthalten sind): 6 Monate
    - Medikationen die Nierenstörungen verursachen könnten: 5xHalbwertszeit
    (10) Für gebärfähige Frauen: ein negativer Serumschwangerschaftstest bei Screening und bereit hochwirksame Methoden zur Empfängnisverhütung während der Studie und bis 60 Tage nach der letzten Dosis des Prüfpräparats anzuwenden. Außerdem müssen die Frauen bereit sein, Schwangerschaftstests während der Einnahme der Studienmedikation durchführen zu lassen. Hochwirksame Methoden zur Empfängnisverhütung sind solche, die eine niedrige Ausfallquote haben (d.h. niedriger als 1% pro Jahr), wenn diese beständig und korrekt angewendet werden, wie z.B. Implantate, Injektionen, kombinierte orale Kontrazeptiva, einige Intrauterinpessare, sexuelle Abstinenz oder ein Partner mit Vasektomie. Patientinnen gelten als gebärfähig, falls bei ihnen keine chirurgische Sterilisation mittels Hysterektomie oder bilaterale Tubenligatur durchgeführt wurde oder sie nicht seit mindestens zwei Jahren in der Post-Menopause sind.
    (11) Männer (ausser die bei denen eine Vasektomie durchgeführt wurde) müssen einwilligen, eine Barrieremethode zur Empfängnisverhütung anzuwenden, während sie Studienmedikation einnehmen
    (12) Gewillt die Sonneneinwirkung angemessen konstant zu halten und kein Solarium oder andere UV Lichtquellen für die Dauer der Studie anzuwenden
    E.4Principal exclusion criteria
    - For females: pregnant or lactating
    - With a diagnosis of guttate, erythrodermic or pustular psoriasis
    - With a hematological abnormality as follows: platelet count < 100,000/mm3, WBC count < 3,000 cells/ mm3, lymphocyte count < 1.000/µl, hemoglobin, hematocrit, or red blood cell count outside 30 % of the upper or lower limits of normal for the lab
    - With a history of malignancies except for non melanoma skin cancer
    - Suffering from significant gastrointestinal problems (ulcers, diarrhea, etc.)
    - Known to have severe renal impairment
    - Are detected to have abnormal liver enzymes
    - With active infectious disease
    -On systemic therapy with drugs that may interfere with the investigational products taken within the defined wash-out period
    - With a history of alcohol or drug abuse
    - Known HIV-positive status or suffering from any other immunosuppressive disease
    - Known to be hypersensitive to ingredients of the investigational products
    - Previous enrolled in this study or participating in any other drug investigational trial within the 30 days (or five half-lives whichever is longer) prior to enrolment.
    - Not willing to give consent for transmission of personal "pseudonymised" data
    - Unable to comply with the requirements of the study or who in the opinion of the investigator should not participate in the study.
    - Previous failed therapy with fumaric acid esters either due to inadequate efficacy or lack of tolerability
    Ausschlusskriterien:
    (1) Bei Frauen: schwanger oder stillend
    (2) Mit einer Diagnose von Psoriasis guttata, erythrodermischer Psoriasis oder Psoriasis pustulosa
    (3) Mit einer folgenden hämatologischen Abnormität: Thrombozytenzahl < 100,000/mm3, Anzahl der weißen Blutkörperchen < 3,000 Zellen/ mm3, Lymphozytenzahl < 1.000/µl, Hämoglobin, Hämatokrit, oder Anzahl der roten Blutkörperchen außerhalb 30 % des oberen oder unteren Normalwertes des Labors
    (4) Mit einer Vorgeschichte von malignen Erkrankungen mit Ausnahme von Nicht-Melanom-Hautkrebs
    (5) Leidet unter bedeutenden gastrointestinalen Problemen (Ulcus, Durchfall usw.)
    (6) Mit bekannter, schwerwiegender renaler Beeinträchtigung
    (7) Nachweis abnormaler Leberenzyme
    (8) Mit aktiver infektiöser Erkrankung
    (9) Systemische Behandlung mit Medikamenten, die die Prüfprodukte, die während der definierten Auswaschphase eingenommen werden, beeinflussen könnten
    (10) Mit einer Vorgeschichte von Alkohol- oder Drogenmissbrauch
    (11) Bekannter HIV-positiver Status oder Patient leidet an einer anderen immunsuppressiven Erkrankung
    (12) Bekannte Hypersensitivität auf Bestandteile der Prüfprodukte
    (13) Frühere Aufnahme in diese Studie oder Teilnahme an einer anderen klinischen Prüfung eines Medikamentes innerhalb von 30 Tagen (oder fünf Halbwertszeiten, welches länger ist) vor Aufnahme in die Studie.
    (14) Nicht bereit, in die Weitergabe von persönlichen, „pseudonymisierten“ Daten einzuwilligen
    (15) Patienten, die nicht fähig sind, den Erfordernissen der Studie nachzukommen oder gemäß der Meinung des Prüfarztes, nicht an der Studie teilnehmen sollten.
    (16) Im Vorfeld nicht erfolgreich durchgeführte Therapie mit Fumarsäure entweder wegen unzureichender Wirksamkeit oder Verträglichkeit
    E.5 End points
    E.5.1Primary end point(s)
    Primary efficacy variables are:
    - PASI 75 (= Response)
    - Proportion of subjects achieving a score of “clear” or ”almost clear” in the Physician’s Global Assessment (PGA)
    Primäre Wirksamkeitsvariablen sind:
    o PASI 75 bei Woche 16 (= Ansprechen (response))
    o Anteil der Patienten, die gemäß ‘Physician’s Global Assessment’ (PGA) in Woche 16 eine Beurteilung von ‚abgeklungen‘ (‘clear’) oder ‚fast abgeklungen‘ (‚almost clear‘) erreichen
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 16
    Woche 16
    E.5.2Secondary end point(s)
    Secondary efficacy variables are:
    - PASI 50, PASI 75, PASI 90, PASI 125
    - Proportion of subjects achieving a score of “clear” or ”almost clear” in the Physician’s Global Assessment (PGA)
    - Body Surface Area (BSA)
    - Treatment Success rate
    - Remission rate
    - Time to Relapse
    - Time to Rebound (worsening of psoriasis over baseline value (PASI > 125%))
    - Patient Benefit Index based on the Patient Need Questionnaire (PNQ) and the Patient Benefit Questionnaire (PBQ)

    E.5.2.1Timepoint(s) of evaluation of this end point
    at week 3, 8 and 16
    Woche 3, 8 und 16

    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 590
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 690
    F.4.2.2In the whole clinical trial 690
    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)
    The investigator will discuss with the patient if further treatment is necessary and prescribe approved therapy as appropriate.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-10-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-10-02
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-10-03
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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