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    Summary
    EudraCT Number:2019-000818-11
    Sponsor's Protocol Code Number:M-41008-48
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-07-26
    Trial 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 ConcernedSpain - AEMPS
    A.2EudraCT number2019-000818-11
    A.3Full title of the trial
    Clinical study to evaluate the efficacy and safety of a combination therapy with dimethyl fumarate (DMF) and NB-UVB phototherapy (versus DMF monotherapy) in adults with moderate-to-severe chronic plaque psoriasis (PHOTOSKILL)
    Estudio clínico para evaluar la eficacia y la seguridad de un tratamiento combinado con dimetilfumarato (DMF) y fototerapia con NB-UVB (frente a DMF en monoterapia) en adultos con psoriasis en placas crónica moderada o grave.(PHOTOSKILL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical study to evaluate the efficacy and safety of a combination therapy with dimethyl fumarate (DMF) and NB-UVB phototherapy (versus DMF monotherapy) in adults with moderate-to-severe chronic plaque psoriasis (PHOTOSKILL)
    Estudio clínico para evaluar la eficacia y la seguridad de un tratamiento combinado con dimetilfumarato (DMF) y fototerapia con NB-UVB (frente a DMF en monoterapia) en adultos con psoriasis en placas crónica moderada o grave.(PHOTOSKILL)
    A.3.2Name or abbreviated title of the trial where available
    PHOTOSKILL study
    Estudio PHOTOSKILL
    A.4.1Sponsor's protocol code numberM-41008-48
    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
    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
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAlmirall
    B.5.2Functional name of contact pointInternat. Clinical Trial Manager
    B.5.3 Address:
    B.5.3.1Street AddressLaureà Miró, 408-410
    B.5.3.2Town/ citySant Feliu de Llobregat
    B.5.3.3Post code08980
    B.5.3.4CountrySpain
    B.5.4Telephone number+34932917403
    B.5.6E-mailsara.herrero@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 Yes
    D.2.1.1.1Trade name Skilarence
    D.2.1.1.2Name of the Marketing Authorisation holderAlmirall, S.A.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameSkilarence
    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 FUMARATE
    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 Yes
    D.2.1.1.1Trade name Skilarence
    D.2.1.1.2Name of the Marketing Authorisation holderAlmirall, S.A.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameSkilarence
    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 FUMARATE
    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.8 Information on Placebo
    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
    Psoriasis en placas crónica moderada o grave.
    E.1.1.1Medical condition in easily understood language
    Moderate to severe chronic plaque psoriasis
    Psoriasis en placas crónica moderada o grave.
    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 20.0
    E.1.2Level LLT
    E.1.2Classification code 10071117
    E.1.2Term Plaque psoriasis
    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
    To assess the efficacy of a DMF/NB-UVB PT combination regimen and DMF treatment alone in patients with moderate-to-severe chronic plaque psoriasis, as assessed by PASI 75 or PASI ≤3.
    Evaluar la eficacia de una pauta combinada de DMF/FT con NB-UVB y el tratamiento con DMF en monoterapia en pacientes con psoriasis en placas crónica moderada o grave, evaluada mediante PASI 75 o PASI ≤ 3.
    E.2.2Secondary objectives of the trial
    1. To assess the efficacy of a DMF/NB-UVB PT combination regimen and DMF treatment alone (as assessed by PASI, BSA, and PGA.
    2. To assess the time to achieve a clinically meaningful improvement (as assessed by PASI) of a DMF/ NB-UVB PT combination regimen and DMF treatment alone.
    3. To assess the efficacy of DMF/ NB-UVB PT combination regimen and DMF treatment alone according to patient-reported outcomes (PRO) (DLQI, Skindex-16, pruritus-VAS, and WPAI).
    4. To assess cost-effectiveness (as assessed by health resources utilisation [HRU] and EQ-5D) of a DMF/ NB-UVB PT combination regimen and DMF treatment alone.
    5. To assess the safety and tolerability of a DMF/ NB-UVB PT combination regimen and DMF treatment alone.
    6. To assess adherence rate and patient satisfaction of a DMF/ NB-UVB PT combination regimen and DMF treatment alone.
    1.Evaluar la eficacia de una pauta combinada de DMF/FTcon NB-UVBy el tratamiento con DMF en monoterapia(evaluada mediante PASI, SCA y PGA).2.Evaluar el tiempo hasta alcanzar una mejora clínicamente significativa(evaluada mediante PASI)de una pauta combinada de DMF/FT con NB-UVB y del tratamiento con DMF en monoterapia.3.Evaluar la eficacia de una pauta combinada de DMF/FTcon NB-UVBy el tratamiento con DMF en monoterapia en función de los resultados notificados por los pacientes(RNP)(DLQI,Skindex-16,EVA-prurito yWPAI).4.Evaluar la relación coste-efectividad (evaluada mediante la utilización de recursos sanitarios[URS]y el cuestionario EQ-5D)de una pauta combinada de DMF/FT NB-UVBy del tratamiento con DMF en monoterapia.5.Evaluar la seguridad y la tolerabilidad de una pauta combinada de DMF/FTcon NB-UVBy del tratamiento con DMF en monoterapia.6.Evaluar la tasa de adherencia y la satisfacción del paciente de una pauta combinada de DMF/FT con NB-UVBy del tratamiento con DMF en monoterapia.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1- Ability to understand and comply with the requirements of the study and communicate with the Investigator, and written, signed and dated informed consent given before any study related activity is performed.
    2-Male or female must be at least 18 years of age at the time of Screening Visit.
    3-Patients diagnosed with chronic plaque psoriasis of at least 6 months prior to the Screening Visit, and stable active plaque-type psoriasis (defined as without clinically significant flares during the 12 weeks before randomisation).
    4-Patients with the severity of psoriasis at Screening and Baseline visits defined by PASI score >5.
    5-Candidates whose disease is eligible for systemic treatment and PT (i.e. with lesions in areas that can be irradiated) at the Screening Visit.
    6-Patients who are PT naïve or who have not had PT at least 6 months before the Screening Visit.
    7-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 (within normal or clinically acceptable range limits) and physical examination (no clinical significant abnormal findings). Investigators are encouraged to consult with the Sponsor if there are questions regarding the significance of any out of range values.
    8-Complete record of at least the last 12 months prior to the Screening Visit of anti-psoriatic previous topical, PT and non-biologic systemic treatments, if any.
    9-Unlikely to conceive, as indicated by at least one “yes” answer to the following questions
    -Patient is a male
    -Patient is a surgically sterilized female by hysterectomy or bilateral tubal ligation
    -Patient is a postmenopausal female ≥45 years of age with >1 year since last menses. If a patient is <45 years of age, or cessation of menses is more than 3 months and less than 1 year, follicle stimulating hormone must be documented as elevated into the postmenopausal range (>60 mIU/mL) at the Screening visit
    -Patient is a non-sterilized and pre-menopausal female using a highly effective medically accepted method of contraception, during the study period and for 60 days after the last dose of the study drug
    10-For female patients of child-bearing potential, a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. Additionally, they must agree to have urine pregnancy tests while on study medication.
    11-Patients willing to keep sun exposure of the trunk and limbs to none or minimal, occasional and unintentional, and not to use tanning booths or other ultraviolet (UV) light sources for the duration of the trial.
    1-Capacidad para comprender y cumplir con los requisitos del estudio y comunicarse con el investigador, y obtención del consentimiento informado escrito, firmado y fechado antes de que pueda realizarse cualquiera de las actividades del estudio.
    2 - Pacientes de sexo masculino o femenino con al menos 18 años de edad en el momento de la visita de selección.
    3 - Pacientes con diagnóstico de psoriasis crónica en placas al menos 6 meses antes de la visita de selección, y psoriasis en placas activa estable (definida como sin brotes clínicamente significativos durante los 12 meses anteriores a la aleatorización).
    4 - Pacientes con una gravedad de la psoriasis en la visita de selección y en la visita inicial definida mediante puntuación PASI > 5.
    5 - Candidatos cuya enfermedad sea apta para tratamiento sistémico y FT (es decir, con lesiones en áreas que puedan irradiarse) en la visita de selección.
    6 - Pacientes que no han recibido previamente tratamiento con FT o que no han recibido FT al menos durante 6 meses antes de la visita de selección.
    7 - Buen estado de salud general, o con una afección médica estable que no se considera probable que interfiera con la realización del estudio clínico, según lo determinado por el investigador en función de los resultados de la historia clínica, los resultados analíticos (dentro de los límites normales o clínicamente aceptables) y la exploración física (sin hallazgos anómalos clínicamente significativos). Se invita a los investigadores a consultar al promotor si existen preguntas en relación con la significación de cualquier valor fuera de los intervalos establecidos.
    8 - Registro completo durante al menos los 12 meses anteriores a la visita de selección de los tratamientos antipsoriásicos tópicos, de FT y los tratamientos sistémicos no biológicos previos, en caso de haberlos.
    9 - Es poco probable que conciba un hijo, según indica una respuesta afirmativa a al menos una de las siguientes preguntas
    - El paciente es de sexo masculino
    - El paciente es una mujer que se ha sometido a esterilización quirúrgica mediante histerectomía o ligadura de trompas bilateral
    - El paciente es una mujer posmenopáusica de ≥ 45 años de edad con > 1 año desde la última menstruación. Si una paciente tiene < 45 años de edad, o la interrupción de la menstruación tiene una duración superior a 3 meses e inferior a 1 año, debe documentarse una elevación de la hormona foliculoestimulante dentro del intervalo de postmenopausia (> 60 mIU/ml) en la visita de selección
    - El paciente es una mujer no esterilizada y premenopáusica que acepta utilizar un método anticonceptivo de gran eficacia y médicamente aceptable durante el periodo del estudio y los 60 días posteriores a la administración de la última dosis del fármaco del estudio
    Nota aclaratoria: Los métodos anticonceptivos de gran eficacia se definen como los métodos con una tasa de fallo inferior al 1 % (p. ej., implantes hormonales, hormonas inyectables, ciertos dispositivos intrauterinos, vasectomía de la pareja o abstinencia sexual) o el uso de dos métodos anticonceptivos (p. ej., un método de barrera [preservativo, diafragma o capuchón cervical] con espermicida y un anticonceptivo hormonal [p. ej., anticonceptivos orales combinados, parche, anillo vaginal, inyectables o implantes])
    10 - Las pacientes de sexo femenino con capacidad para procrear deben obtener un resultado negativo en la prueba de embarazo en suero en la visita de selección y un resultado negativo en la prueba de embarazo en orina en la visita inicial. Adicionalmente, deben aceptar someterse a pruebas de embarazo en orina mientras reciban la medicación del estudio.
    11 - Pacientes dispuestos a evitar o a reducir al mínimo, de manera ocasional y no intencionada, la exposición solar del tronco y las extremidades y a no usar cabinas de bronceado u otras fuentes de luz ultravioleta (UV) durante todo el estudio.
    E.4Principal exclusion criteria
    1-Female patients who are currently pregnant, who intend to become pregnant during the course of the study, or who are breastfeeding, unwillingness/inability to use appropriate measures of contraception
    2- Patients with a diagnosis of flexural, guttate, erythrodermic or pustular psoriasis
    3- Patients with a diagnosis and/or signs/symptoms suggestive of active psoriatic arthritis
    4- Drug-induced psoriasis (i.e., a new onset or current exacerbation of psoriasis from beta-blockers, calcium channel blockers, or lithium)
    5-History or evidence of skin disease (atopic dermatitis, eczema) or conditions (scarring, open wounds) other than chronic plaque-type psoriasis that might interfere with the study conduct or evaluations, or which exposes the patient to unacceptable risk by study participation
    6-Patients with a haematological abnormality at the Screening Visit as follows: platelet count <100,000/mm3, white blood cells (WBC) count < 3,000 cells/ mm3, lymphocyte count < 1,000/μL, haemoglobin, haematocrit, or red blood cell count outside 30% of the upper or lower limits of normal
    for the laboratory.
    7-History or concurrent malignancy (excluding successfully treated basal cell carcinoma, squamous cell carcinoma of the skin in situ, squamous cell carcinoma with no evidence of recurrence within 5 years or carcinoma in situ of the cervix that has been adequately treated).
    8- Presence of severe photodamage, actinic keratosis and/or clinically/histologically atypical moles.
    9- Patients suffering from active significant gastrointestinal problems (ulcers, diarrhoea, etc.).
    10-Patients with severe renal impairment (creatinine clearance <30 mL/min, estimated glomerular filtration rate (eGFR) using CKD-EPI Creatinine Equation or significant proteinuria (3+ or higher)
    11-Patients with abnormal liver enzymes:
    -if an enzyme was >3x the upper limit of the normal range (ULN): aspartate amino transferase (AST or SGOT), alanine amino transferase (ALT or SGPT), gamma-glutamyl-transferase (GGT), alkaline phosphatase (ALP)
    - if bilirubin was >2x ULN, for the other liver enzymes >2x ULN was exclusionary
    12-Patients with active infectious disease
    13- Patients on systemic therapy
    14- Patients with concomitant treatment with immunomodulating or immunosuppressive medication, or systemic corticosteroids
    15- History of hypersensitivity or allergy to the study drugs or its excipients
    16- Patients with history or evidence/indication of current drug and/or alcohol abuse or dependence, according to the judgment of the Investigator
    17- Patients with HIV-positive status or any other immunosuppressive disease
    18-Patients who have had a live vaccination within 4 weeks prior to the Baseline Visit, or intend to have a live vaccination during the course of the study, or have participated in a vaccine clinical study within 12 weeks of randomization
    19-Patient who intend to use any concomitant medication not permitted by this study or who have not undergone the required washout period, prior to the Baseline Visit, for a particular prohibited medication:
    -Topical psoriasis treatment (e.g. topical corticosteroids, vitamin A analogues, vitamin D analogues, coal tar, anthracene derivatives, salicylic acid preparations): 2 weeks
    -PT (other than the study PT, e.g. Psoralen-UVA therapy, tanning salon or homeadministered UVB): 6 months
    -Conventional systemic anti-psoriatic drugs, excluding fumarate-based drugs and PT: 4 weeks
    -Any other immunosuppressive medication (e.g. cytostatics, etc.): 6 months
    20- Patients who are hypersensitive to ingredients of the study drugs
    21- Patients 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 enrollment.
    22- Concurrent systematic therapy
    23- Patients with photosensitivity: hypersensitivity to sunlight or UVB light of any type; history of Lupus, polymorphic light eruption (PMLE), or any disease known to be worsened by UV light exposure
    24- Patients that intake concomitant medications that are known to be able to induce photosensitivity
    25-Patients with previous exposure to fumarate-based drug or a biologic systemic treatment (e.g. tumour necrosis factor-alpha inhibitors, IL-17 inhibitors, IL-17R inhibitors, IL-12/23 p40 inhibitors, IL-23p19 inhibitors or experimental biological product)
    26- Patients who failed to respond, did not tolerate, had relevant side-effects or with contra-indication to NB-UVB in the past
    27- Patients who are not eligible for PT according to the Investigator (e.g. patients with severe involvement of the scalp and/or skin folds).
    28- Patients who do not have logistic availability to fulfil all the PT sessions required in the study
    29- Patients previously randomised in the current study
    30- Patients who are employee or relative of employees at the research site or Almirall
    31-Patient with any other serious or uncontrolled physical or mental dysfunction
    1-Mujeres embarazadas/que tengan previsto quedarse embarazadas durante el estudio/en periodo de lactancia o no-disposición/incapacidad) para usar métodos anticonceptivos apropiados.
    2-Con diagnóstico de psoriasis flexural/guttata/eritrodérmica o pustulosa en visita de selección(VS).
    3-Con diagnóstico y/o signos/síntomas de artritis psoriásica activa
    4-Psoriasis inducida por fármacos (p.ej. psoriasis de nueva aparición o reagudización por: betabloqueantes, antagonistas del calcio o litio) en VS.
    5–Antecedentes/signos de enfermedad de la piel(dermatitis atópica/eczema) o afecciones (cicatrices/heridas abiertas) diferentes a la psoriasis crónica en placa que puedan interferir con la realización del estudio, o que exponga al paciente a un riesgo inaceptable.
    6-Pacientes que en VS tengan recuento plaquetario <100.000/mm3, leucocitos <3.000 células/mm3, linfocitos <1.000/μl, hemoglobina/hematocrito/eritrocitos >30% del límite superior o <30 % límite inferior de normalidad.
    7-Antecedentes de neoplasia maligna previa/concomitante (excepto casos tratados de carcinoma: basocelular, epidermoide de piel in situ, epidermoide sin signos de recidiva durante 5 años o cervical in situ tratado adecuadamente).
    8-Presencia de fotolesiones graves/queratosis actínica y/o lunares clínica/ histológicamente atípicos en VS.
    9-Pacientes con problemas gastrointestinales significativos (úlceras/diarrea/etc) en VS.
    10-Pacientes con insuficiencia renal grave en VS (aclaramiento de creatinina <30ml/min, tasa de filtración glomerular estimada [ecuación CKD-EPI] o proteinuria significativa (≥3) en VS.
    11-Valores anómalos de enzimas hepáticas en VS:
    -valor >3x el límite superior de normalidad (LSN): aspartato aminotransferasa, alanina aminotransferasa, gamma-glutamil transferasa, fosfatasa alcalina.
    -valor bilirrubina >2x LSN, para el resto de enzimas valor >2x LSN.
    12-Pacientes con enfermedad infecciosa activa en VS.
    13-Pacientes en tratamiento sistémico con fármacos que puedan interferir con los del estudio si se toman en el periodo de lavado.
    14-Pacientes en tratamiento concomitante con medicación inmunomoduladora/ inmunosupresora o corticosteroides sistémicos.
    15-Antecedentes de hipersensibilidad/alergia a los fármacos del estudio o sus excipientes.
    16-Pacientes con antecedentes (2 años anteriores a VS) o signos/indicios de alcoholismo/toxicomanía actuales, según criterio investigador.
    17-Pacientes con serología positiva para VIH o con otra enfermedad inmunosupresora.
    18-Pacientes que han recibido una vacuna viva 4 semanas anteriores a la visita basal, o prevén recibirla durante el estudio, o han participado en un estudio clínico con una vacuna en 12 semanas anteriores a la aleatorización.
    19-Pacientes que prevén usar cualquier medicación concomitante no permitida o que no hayan tenido el periodo de lavado para la medicación no permitida (antes de la visita basal):
    -Tratamiento tópico para psoriasis (p. ej., corticosteroides tópicos, análogos de vitamina A/D, alquitrán de hulla, derivados de antraceno o de ácido salicílico):2 semanas
    -FT (diferente a FT del estudio, p. ej., psoralenos más radiación UV, centro de bronceado o UVB administrada en el domicilio):6 meses
    -Fármacos antipsoriásicos sistémicos convencionales, excepto fumaratos y FT:4 semanas
    -Cualquier otra medicación inmunosupresora (p.ej., fármacos citostáticos):6 meses
    20-Hipersensibilidad a los ingredientes de los fármacos del estudio.
    21-Pacientes incluidos anteriormente en este estudio o que participaron en otro estudio de investigación clínica en los 30 días (o 5 semividas, el periodo más prolongado) anteriores a la inclusión en el estudio.
    22-Tratamiento sistémico concomitante que pueda interferir con los fármacos del estudio si se toman dentro del periodo de lavado.
    23-Pacientes con fotosensibilidad: hipersensibilidad a la luz solar/UVB de cualquier tipo; antecedentes de Lupus, fotodermatosis polimorfa o cualquier enfermedad que empeora con la luz UV.
    24-Pacientes con medicaciones concomitantes que pueden inducir fotosensibilidad.
    25-Pacientes con exposición previa a fumaratos o a un tratamiento biológico sistémico (p.ej., inhibidores de: factor de necrosis tumoral alfa, IL-17, IL-17R, IL-12/23 p40, IL-23p19, o un producto biológico en investigación).
    26-Pacientes que no respondieron/toleraron o presentaron efectos secundarios significativos o contraindicación a NB-UVB en el pasado.
    27-Pacientes no aptos para FT según criterio investigador.
    28-Los pacientes sin disponibilidad logística para completar las sesiones de FT del estudio.
    29-Pacientes aleatorizados previamente en el estudio actual.
    30-Empleados/familiares de empleados del centro de investigación o Almirall.
    31-Pacientes con otra disfunción física/mental grave o no controlada que, a criterio investigador, suponga un riesgo para el paciente, sea un elemento de confusión para los resultados o impida que el paciente cumpla los requisitos del estudio
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of patients achieving “PASI 75 response OR PASI ≤3” at 24 weeks of treatment
    Proporción de pacientes que alcanzan una “respuesta PASI 75 O PASI ≤ 3” a las 24 semanas de tratamiento (criterio de valoración compuesto).
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 24
    24 semanas
    E.5.2Secondary end point(s)
    Efficacy endpoints
    -Proportion of patients achieving a PASI 75 response at 24 weeks of treatment.
    -Proportion of patients achieving an absolute PASI score of ≤3 at 24 weeks of treatment.
    -Proportion (and number) of patients achieving PASI 75, PASI 90 responses as well as absolute PASI score of ≤5, ≤3 and ≤1 all visits*.
    -Absolute PASI score and percentage change from baseline in the absolute PASI score at all visits*.
    -Proportion (and number) of patients with a PGA score of 0 or 1 (‘clear’ or ‘almost clear’) at all visits*.
    -Absolute PGA score and change from baseline in the absolute PGA score at each visit*.
    -Absolute BSA score and change from baseline in the absolute BSA score at each visit*.
    -Time to achieve the primary composite endpoint (PASI 75 response OR to PASI score ≤3)
    -Time to PASI 75 response.
    -Time to PASI score ≤ 3.
    -Absolute DLQI score and percentage change from baseline in the absolute DLQI score at all visits*.
    -Proportion of patients achieving a DLQI score of 0 or 1 at all visits*.
    -Absolute Skindex-16 score and change from baseline in the absolute Skindex-16 score at all visits*.
    -Absolute pruritus-VAS score and change from baseline in the absolute pruritus-VAS score at all visits*.
    -Absolute WPAI score and change from baseline in the absolute WPAI score at all visits*
    * When the data is collected
    -HRU related to psoriasis collected at Week 24:
    • Number of visits related to psoriasis (including unscheduled)
    • Treatments related to psoriasis (including dose, route, frequency, duration, onset date, end date, and reasons for onset and discontinuation
    • Number of hospitalisation/s related to psoriasis (if any, number of hospitalisations and length [days])
    • Number of unscheduled/emergency room visits to the general practitioner/dermatologist related to psoriasis (if any, number [days]
    • Diagnostic procedures related to psoriasis (clinical examination, laboratory controls, biopsy [if any], others)
    • Percentage of HRU related to adverse reactions (ARs) to psoriasis-treatments generating costs (i.e. concomitant treatments, etc.)
    - Quality Adjusted Life Year (QALY) for 24 weeks of treatment will be calculated using the EQ-5D score
    - Proporción de pacientes que alcanzan una respuesta PASI 75 a las 24 semanas de tratamiento.
    - Proporción de pacientes que alcanzan una puntuación PASI absoluta de ≤ 3 a las 24 semanas de tratamiento.
    - Proporción (y número) de pacientes que alcanzan una respuesta PASI 75 y PASI 90, así como una puntuación PASI absoluta de ≤ 5, ≤ 3 y ≤ 1 en todas las visitas*.
    - Puntuación PASI absoluta y cambio porcentual respecto al periodo basal en la puntuación PASI absoluta en todas las visitas*.
    - Proporción (y número) de pacientes con una puntuación PGA de 0 o 1 («blanqueada» o
    «casi blanqueada») en todas las visitas*.
    - Puntuación PGA absoluta y cambio respecto al inicio en la puntuación PGA absoluta en cada visita*.
    - Puntuación SCA absoluta y cambio respecto al inicio en la puntuación SCA absoluta en cada visita*.
    - Tiempo hasta alcanzar el criterio principal de valoración compuesto (respuesta PASI 75 O hasta puntuación PASI ≤ 3)
    - Tiempo hasta respuesta PASI 75.
    - Tiempo hasta puntuación PASI ≤ 3.
    - Puntuación DLQI absoluta y cambio porcentual respecto al inicio en la puntuación DLQI absoluta en todas las visitas*.
    - Proporción de pacientes que alcanzan una puntuación DLQI de 0 o 1 en todas las visitas*.
    - Puntuación Skindex-16 absoluta y cambio respecto al inicio en la puntuación Skindex-16 absoluta en todas las visitas*.
    - Puntuación EVA-prurito absoluta y cambio respecto al periodo basal en la puntuación EVA-prurito absoluta en todas las visitas*.
    - Puntuación WPAI absoluta y cambio respecto al inicio en la puntuación WPAI absoluta en todas las visitas*.
    *Cuándo se recogen los datos
    - Datos de URS relacionada con la psoriasis recogidos en la semana 24:
    • Número de visitas relacionadas con la psoriasis (incluyendo visitas no programadas)
    • Tratamientos relacionados con la psoriasis (incluyendo dosis, vía de administración, frecuencia, duración, fecha de inicio, fecha de finalización y motivos para el inicio y la suspensión)
    • Número de hospitalizaciones relacionadas con la psoriasis (en caso de haberlas, número de hospitalizaciones y duración [días])
    • Número de visitas no programadas/al servicio de urgencias al médico de cabecera/dermatólogo relacionadas con la psoriasis (en caso de haberlas, número y duración [días])
    • Procedimientos diagnósticos relacionados con la psoriasis (exploración clínica, controles analíticos, biopsia [en caso de haberla], otros)
    • Porcentaje de URS relacionada con reacciones adversas (RA) a tratamientos contra la psoriasis que genere costes (es decir, tratamientos concomitantes, etc.)
    -El año de vida ajustado por calidad (QALY) durante 24 semanas de tratamiento se calculará utilizando la puntuación EQ-5D
    E.5.2.1Timepoint(s) of evaluation of this end point
    Sec effi endpoints will be analysed by statist per trat and visit.Or expl purposes,the key seco effi vabl will be comp between arms A and B at each visit by means of,an ANCOVA mod in case of contis vabl,using the trat as factor,and the PASI baseline score as covariate.All binary effi vabl will be analy for the comp between trat.at diff time points by Chi-square test.Analy of the sec effic endpoints will be based on the mITT.Key sec effic endpoints will be also analy for the PP. Effi data for the sec effic analy will not be imputed.In addition,for key sec effi endpoints,effi values will be imputed using the NRI and MI methods.The sec effi analy will be given in the SAP.HRU and QALY results will be calculated as part of the cost-effec analy that will be done in Almirall.;will be includedSAP
    Los crit secundarios de efic se analizarán por estadísticos descriptivos por grupo de tratamiento,en cada visita.Comparación de variables sec de efic entre los grupos A y B en cada visita con un mod ANCOVA en variables cont,eltratamiento como factor y la puntuación PASI inicial como covariable. Analisis de las variables de efic binarias comparando los ttmto en diferentes momentos de análisis por Chicuadrado. La valoración de efic de crit sec se hará en pobl IITm y tmb para pobl PP.No se imputarán los datos de efic no disponibles.Para los crit sec de valoración de efic se imputarán los valores de efic no disponibles utilizando los métodos de PSR y de IM.Se calcularán los resultados de URS y QALY como parte del análisis de la relación coste-efec en Almirall;se incluirán en un PAE indep
    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 Yes
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Dimethyl Fumarate as monotherapy
    E.8.2.4Number of treatment arms in the trial2
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA21
    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 No
    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
    ULTIMA VISITA ULTIMO PACIENTE EN EL ENSAYO
    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 months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days0
    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: 130
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 150
    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)
    None
    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 Decision2019-09-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-09-06
    P. End of Trial
    P.End of Trial StatusOngoing
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