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    Summary
    EudraCT Number:2017-001489-53
    Sponsor's Protocol Code Number:CNTO1275SLE3001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-03-14
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2017-001489-53
    A.3Full title of the trial
    A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Subjects with Active Systemic Lupus Erythematosus
    Estudio multicéntrico, aleatorizado, en doble ciego, controlado con placebo y de grupos paralelos, de ustekinumab en sujetos con lupus eritematoso sistémico activo
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of Ustekinumab in Subjects with Active Systemic Lupus Erythematosus
    Estudio de Ustekinumab en sujetos con lupus eritematoso sistémico activo
    A.3.2Name or abbreviated title of the trial where available
    LOTUS
    A.4.1Sponsor's protocol code numberCNTO1275SLE3001
    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 SponsorJanssen-Cilag International NV
    B.1.3.4CountryBelgium
    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 supportJanssen Research & Development
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPAREXEL International LLC
    B.5.2Functional name of contact point-
    B.5.3 Address:
    B.5.3.1Street Address-
    B.5.3.2Town/ city-
    B.5.3.3Post code-
    B.5.3.4CountrySpain
    B.5.4Telephone number+34913913443
    B.5.5Fax number-
    B.5.6E-mailclinicaltrial.enquiries@parexel.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 Stelara
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    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.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNustekinumab
    D.3.9.1CAS number 815610-63-0
    D.3.9.2Current sponsor codeCNTO1275
    D.3.9.3Other descriptive nameUSTEKINUMAB
    D.3.9.4EV Substance CodeSUB27761
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number90
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeMonoclonal Antibody
    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 Stelara
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNustekinumab
    D.3.9.1CAS number 815610-63-0
    D.3.9.2Current sponsor codeCNTO1275
    D.3.9.3Other descriptive nameUSTEKINUMAB
    D.3.9.4EV Substance CodeSUB27761
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeMonoclonal antibody
    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 placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Systemic Lupus Erythematosus
    Lupus eritematoso sistémico
    E.1.1.1Medical condition in easily understood language
    Lupus
    Lupus
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10042945
    E.1.2Term Systemic lupus erythematosus
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    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 objective is to evaluate the efficacy of ustekinumab in
    subjects with active systemic lupus erythematosus (SLE) who have not
    adequately responded to one or more standard-of-care treatments.
    El objetivo principal es evaluar la eficacia del ustekinumab en sujetos con lupus eritematoso sistémico (systemic lupus erythematosus, SLE) activo que no han respondido de manera adecuada a uno o más tratamientos habituales.
    E.2.2Secondary objectives of the trial
    The secondary objectives are to evaluate the following in subjects with active SLE despite receiving one or more standard-of-care treatments:
    1. Reduction in SLE flares
    2. Improvement in global and organ-specific (mucocutaneous, musculoskeletal, etc) measures of SLE disease activity
    3. Glucocorticoid sparing
    Los objetivos secundarios son evaluar lo siguiente en sujetos que presentan lupus eritematoso sistémico activo a pesar de recibir uno o más tratamientos habituales:
    1. Reducción de los brotes de lupus eritematoso sistémico
    2. Mejoría de las medidas de actividad de la enfermedad en el lupus eritematoso sistémico, generales y por aparatos u órganos (mucocutáneas, musculoesqueléticas, etc.)
    3. Ahorro de glucocorticoides
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Cutaneous Disease Photography Substudy:
    In order to correlate CLASI assessment findings with images of cutaneous lupus, a cutaneous disease photography substudy will be performed at selected sites on a subset of subjects with cutaneous lupus present at baseline.

    Pharmacogenomic (DNA) Evaluations:
    DNA samples will be analyzed for identification of genetic factors to better understand the molecular effects of ustekinumab and/or SLE, and to evaluate markers that can predict clinical response. Genetic (DNA) research may consist of the analysis of 1 or more candidate genes or analysis of the entire genome (as appropriate) in relation to ustekinumab and/or SLE.
    Subestudio de fotografías de la enfermedad cutánea:
    Con objeto de efectuar una correlación entre los hallazgos de la evaluación CLASI con las imágenes del lupus cutáneo, se va llevar a cabo un subestudio de fotografías de la enfermedad cutánea, en determinados centros y en un subgrupo de sujetos con lupus cutáneo en el momento basal.
    Evaluaciones farmacogenómicas (DNA):
    Se analizarán muestras de DNA para identificar aquellos factores genéticos que permitan conocer mejor los efectos moleculares de ustekinumab y/o del lupus eritematoso sistémico (LES), y para evaluar los posibles marcadores que puedan predecir la respuesta clínica. Esta investigación genética (DNA) podría consistir en el análisis de uno o más genes candidatos o del genoma completo (según proceda) en relación al ustekinumab y/o el lupus eritematoso sistémico.
    E.3Principal inclusion criteria
    • Between 16 (unless restricted by local requirements) and 75 years of age, inclusive.
    • Diagnosis of SLE made or confirmed by a physician experienced in the treatment of SLE.
    • Documented medical history that subject met the SLICC classification criteria for SLE at least 3 months prior to first dose of study agent.
    • At least 1 well-documented unequivocally positive test in medical history and detected during screening, for at least 1 of the following autoantibodies: ANA, anti-dsDNA, and/or anti-Smith.
    • Have at least 1 BILAG A and/or 2 BILAG B domain scores observed during screening.
    • Have a CLASI activity score of at least 4 or at least 4 joints with pain and signs of inflammation at screening or at Week 0, or both.
    • Demonstrate active disease based on SLEDAI-2K score ≥6 observed during screening. Must also have SLEDAI-2K ≥4 for clinical features present at Week 0 prior to randomization.
    • Must be receiving one or more of the following protocol-permitted, systemic standard-of-care treatments:
    a) Oral glucocorticoids (average daily dose ≤20 mg of prednisone or equivalent) for ≥6 weeks and at a stable dose ≥4 weeks prior to first dose of study agent.
    - If currently not using oral glucocorticoids, must not have received them for ≥6 weeks prior to the first dose of study agent.
    b) Antimalarials for ≥12 weeks and at a stable dose for ≥6 weeks prior to first dose of study agent
    c) If using one or more of the following immunomodulatory drugs, must be receiving for ≥12 weeks and be on a stable dose for ≥6 weeks prior to first dose of study agent:
    -MMF ≤2 g/day
    -MPA ≤1.5 g/day
    -AZA /6-MP ≤2 mg/kg/day; up to 100 mg/day for subjects weighing ≤50 kg
    -Oral MTX ≤25 mg/Week or SC or intramuscular (IM) MTX ≤20 mg/Week with concomitant folic acid or folinic acid.
    If the subject is using concomitantly 2 or more of the immunomodulatory drugs listed above (MMF, MPA, AZA, 6-MP, MTX), the suitability of the subject to participate in the study must be discussed with the medical monitor and/or sponsor before the subject is randomized.
    • Before randomization, a woman must be either:
    a. Not of childbearing potential, or
    b. Of childbearing potential:
    -Practicing a highly effective method of contraception
    -Agrees to remain on a highly effective method of contraception throughout the study and for at least 16 weeks after the last dose of study agent.
    • A woman of childbearing potential must have a negative urine pregnancy tests
    • beta-hCG obtained during screening and at Week 0 before the first dose of study agent.
    • A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 4 months after receiving the last dose of study agent.
    • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
    • A man who is sexually active with a woman who is pregnant must use a condom and all men must not donate sperm during the study and for 20 weeks after receiving the last dose of study agent.
    • Subjects must have laboratory test results within the following parameters at
    screening:
    - Hemoglobin ≥8.0 g/dL (SI: ≥ 80 g/L)
    - Lymphocytes ≥0.5 x 103 /microL (SI: ≥0.5 GI/L)
    - Neutrophils ≥1.0 x 103 / microL (SI: ≥1.0 GI/L)
    - Platelets ≥75 x 103 /microL (SI: ≥ 75 GI/L)
    - Serum creatinine ≤1.8 mg/dL (SI: ≥ 159 micromol/L)
    - AST and ALT<or= 3 x ULN
    If any other labs are grade 3 or above, this must be discussed with the
    medical monitor.
    For rest of Inclusion criteria and/or more details on the above, please
    refer to the study protocol.
    • Edad comprendida entre 16 (salvo si las normativas locales exigieran otra cosa) y 75 años.
    • Diagnóstico de LES formulado o confirmado por un médico con experiencia en el tratamiento del LES.
    • Historia médica documentada de que el sujeto cumple los criterios de la clasificación SLICC de SLE desde como mínimo 3 meses antes de la primera dosis del agente del estudio.
    • Como mínimo un resultado inequívocamente positivo y bien documentado en la historia médica, y observado durante los exámenes de selección, de como mínimo 1 de los siguientes autoanticuerpos: ANA, anti-dsDNA y/o anti-Smith.
    • Presentación durante los exámenes de selección de como mínimo 1 dominio con puntuación BILAG A y/o 2 dominios con puntuación BILAG B en la evaluación de la selección.
    • Puntuación de actividad CLASI de como mínimo 4 o como mínimo 4 articulaciones con dolor y signos de inflamación en la selección o en la Semana 0, o en ambos momentos.
    • Demostración de actividad de la enfermedad según una puntuación SLEDAI-2K ≥6 observada durante la selección. También deberá mostrar una SLEDAI-2K ≥4 en las características clínicas presentes en la Semana 0, antes de la aleatorización.
    • Deberá estar recibiendo uno o más de los siguientes tratamientos sistémicos habituales permitidos por el protocolo:
    a) Glucocorticoides orales (dosis diaria media ≤20 mg de prednisona o equivalente) desde ≥6 semanas antes y a dosis estable desde ≥4 semanas antes de la primera dosis del agente del estudio.
    - Si actualmente no está en tratamiento con glucocorticoides orales, no deberá haberlos recibido desde ≥6 semanas antes de la primera dosis del agente del estudio.
    b) Antipalúdicos ≥12 semanas y a dosis estable desde ≥6 semanas antes de la primera dosis del agente del estudio
    c) Si está en tratamiento con uno o más de los siguientes inmunomoduladores, deberá estar recibiéndolos desde ≥12 semanas antes y estar con una dosis estable desde ≥6 semanas antes de la primera dosis del agente del estudio:
    - MMF ≤2 g/día
    - MPA ≤1.5 g/día
    - AZA /6-MP ≤2 mg/kg/día, con un máximo de 100 mg/día en los sujetos de peso ≤50 kg
    - MTX oral ≤25 mg/semana o MTX SC o intramuscular (IM) ≤20 mg/semana, junto con la administración concomitante de ácido fólico o ácido folínico.
    Si el sujeto está recibiendo concomitantemente dos o más de los inmunomoduladores antes listados (MMF, MPA, AZA, 6-MP, MTX), antes de la aleatorización del sujeto deberá discutirse su adecuación para participar en el estudio con el monitor médico y/o el promotor.
    • Antes de poder ser aleatorizadas, las mujeres:
    a. No podrán ser potencialmente fértiles, o
    b. Si son potencialmente fértiles, deberán:
    - Estar practicando un método anticonceptivo altamente efectivo
    - Mostrar su conformidad en seguir utilizando un método anticonceptivo altamente efectivo durante el estudio y hasta transcurridas como mínimo 16 semanas de la última dosis del agente del estudio.
    • Las mujeres potencialmente fértiles deben arrojar un resultado negativo en una prueba de embarazo en orina
    • Negatividad de una prueba de embarazo de la beta-hCG durante la selección y en la Semana 0, antes de la primera dosis del agente del estudio.
    • Las mujeres deberán mostrar su conformidad en no donar óvulos a fines de reproducción asistida durante el estudio y los 4 meses siguientes a la última dosis del agente del estudio.
    • Los hombres sexualmente activos con mujeres potencialmente fértiles y no sometidos a vasectomía deberán mostrar su conformidad en utilizar un método anticonceptivo de barrera.
    • Los hombres sexualmente activos con mujeres embarazadas deberán utilizar preservativos; por otro lado, los hombres (todos) no podrán donar semen durante el estudio y las 20 semanas siguientes a la última dosis del agente del estudio.
    • Los sujetos deberán presentar los siguientes resultados de laboratorio en los parámetros de la selección:
    - Hemoglobina ≥8,0 g/dL (SI: ≥ 80 g/L)
    - Linfocitos ≥0,5 x 103 /microL (SI: ≥0,5 GI/L)
    - Neutrófilos ≥1,0 x 103 / microL (SI: ≥1,0 GI/L)
    - Plaquetas ≥75 x 103 /microL (SI: ≥ 75 GI/L)
    - Creatinina sérica ≤1,8 mg/dL (SI: ≥ 159 micromol/L)
    - AST y ALT ≤3 x límite superior de la normalidad (UNL)
    Si algún otro valor de laboratorio es grado 3 o superior, deberá discutirse con el monitor médico.
    Para el resto de los criterios de inclusión y/o una mayor información sobre lo anterior, sírvanse consultar el protocolo del estudio.
    E.4Principal exclusion criteria
    • Has any unstable or progressive manifestation of SLE that is likely to warrant escalation in therapy beyond permitted background medications
    • Has other inflammatory disease that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), PsA, RA/lupus overlap, psoriasis, Crohn’s disease, or active Lyme disease
    • Is pregnant, nursing, or planning a pregnancy or planning to father a child while enrolled in the study or within 4 months after receiving the last administration of study agent
    • Has received systemic immunomodulatory agents other than those described in inclusion criteria within 3 months prior to the first dose of study agent
    • Has used oral cyclophosphamide within 90 days or IV cyclophosphamide within 180 days of starting screening
    • Exclusions for treatment with B-cell targeted therapies:
    a. Treatment with a single B-cell targeted therapy within 3 months prior to first dose of study agent.
    b. Treatment with >1 previous B-cell targeting therapy within 6 months prior to first dose of study agent.
    c. Treatment with B-cell depleting therapy within 12 months prior to first dose of study agent, or have evidence of continued B-cell depletion following such therapy
    • Has ever received ustekinumab
    • Has received prior immunomodulatory biologic therapy not described in Section 8.1.7 of protocol less than 5 half-lives or 3 months, whichever is longer, prior to first dose of the study agent.
    • Has received ACTH administered by injection within 1 month prior to the first administration of study agent
    • Has received topical cream/ointment preparations of cyclosporine A, or other topical immunomodulatory agents within 4 weeks prior to the first administration of study agent
    • Is currently receiving venom immunotherapy
    • Subjects likely to require multiple courses of systemic steroids for reasons other than SLE
    • Has received epidural, IV, IM, intra-articular (IA), intrabursal, or intralesional admin of glucocorticoids within 6 weeks prior to the first administration of study agent
    • BCG vaccination within 12 months of screening
    • Live virus or live bacterial vaccination within 16 weeks prior to the first administration of study agent
    • History of active granulomatous infection, including histoplasmosis, or coccidioidomycosis
    • Chest radiograph within 3 months prior to the first dose that shows an abnormality suggestive of a malignancy or current active infection, including TB
    • A nontuberculous mycobacterial infection or opportunistic infection
    • A history of, or ongoing, chronic or recurrent infectious disease
    • History of HIV antibody positive, or tests positive for HIV at screening
    • Hepatitis B infection. Subjects must undergo screening for hepatitis B virus
    • Seropositive for antibodies to hepatitis C virus (HCV), unless has 2 negative HCV RNA test results 6 months apart prior to screening and has a third negative HCV RNA test result at screening
    • Has experienced a recent single dermatomal herpes zoster eruption within the past 4 months. Has ever had multi-dermatomal herpes zoster or CNS zoster infection
    • Within 2 months prior to first administration of study agent, has had a serious infection, or has been hospitalized for an infection, or has been treated with IV antibiotics for an infection. Less serious infections need not be considered exclusionary at the discretion of the Investigator
    • History or suspected occurrence of drug-induced lupus
    • Has inherited complement deficiency or combined variable immunodeficiency
    • Urinary protein level of >4g/day or protein/creatinine ratio estimating >4g/day equivalent proteinuria
    • History of catastrophic antiphospholipid syndrome
    • Has a known hypersensitivity to human immunoglobulin proteins
    • Any major illness/condition or evidence of an unstable clinical condition, disease of any organ system, or active acute or chronic infection/infectious illness
    • Has had major surgery within 1 month before screening, or will not have fully recovered from surgery, or has major surgery planned during the time the subject is expected to participate in the study or within 1 month after the last dose of study agent administration
    • Has a transplanted organ
    • Uses semipermanently attached wigs that would interfere with scoring of cutaneous disease
    • Has or has had a substance abuse (drug or alcohol) problem within the previous 3 years
    • Presence or history of malignancy within 5 years before screening. Note cervical carcinoma and skin cancer exceptions per protocol for malignancy exclusion
    • Has a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease
    • Use of IV gamma globulin, apheresis therapy or immunoadsorption within 6 months prior to study agent and 4 months after last dose
    • Has ever received stem cell transplantation
    For rest of criteria or more details, please see the protocol.
    Cuadro inestable o progresivo de LES que precise incremento de su tratamiento (tto) más allá de la medicación de fondo permitida.
    Otra enfermedad inflamatoria que pudiera actuar como factor de confusión en la evaluación de la eficacia del tto, tales como, entre otras, artritis reumatoide, artritis psoriásica, síndrome mixto de artritis reumatoide/lupus, psoriasis, enfermedad de Crohn o enfermedad de Lyme activa.
    Mujer embarazada, amamantando o planeando quedarse embarazada u hombre planeando engendrar durante su participación en el estudio o en los 4 meses tras la última dosis del estudio.
    Inmunomoduladores sistémicos distintos de los descritos en los crit. de inclusión en los 3 meses anteriores a la primera dosis del estudio.
    Ciclofosfamida oral en los 90 días o ciclofosfamida i.v. en los 180 días anteriores al inicio de la selección.
    En cuanto al tto con agentes dirigidos a los linfocitos B:
    a. Recepción de un sólo tto dirigido a los linfocitos B en los 3 meses anteriores a la primera dosis del estudio.
    b. Recepción de más de un tto previo dirigido los linfocitos B en los 6 meses anteriores a la primera dosis del estudio.
    c. Recepción de tto de depleción de los linfocitos B en los 12 meses anteriores a la primera dosis del estudio o evidencia de persistencia de la depleción de linfocitos B después de dicho tto.
    Recepción de ustekinumab en algún momento.
    Recepción previa de tto biológico con inmunomoduladores no descritos en la Sección 8.1.7 del protocolo en un plazo menor a 5 semividas del producto en cuestión o a 3 meses, eligiéndose el mayor de estos periodos, antes de la primera dosis del estudio.
    Recepción de ACTH inyectable en el mes antes de la primera dosis del estudio.
    Recepción de preparados tópicos de ciclosporina A u otros inmunomoduladores tópicos en las 4 semanas anteriores a la primera dosis del estudio.
    En tto actualmente con inmunoterapia frente a picaduras o mordeduras.
    Probabilidad de requerir ciclos repetidos de corticosteroides sistémicos por razones distintas del LES.
    Recepción de glucocorticoides por vía epidural, IV, IM, intra-articular, intrabursal o intralesional en el las 6 semanas anteriores a la primera dosis del estudio.
    Vacunación con BCG en los 12 meses anteriores a la selección.
    Vacunación con virus o bacterias vivos en las 16 semanas anteriores a la primera dosis del estudio.
    Antecedentes de infección granulomatosa activa, tal como histoplasmosis o coccidioidomicosis.
    Radiografía de tórax en los 3 meses anteriores a la primera dosis del agente del estudio que muestra imágenes sugerentes de neoplasia maligna o de infección activa actual, incluida TB.
    Infección por micobacterias no tuberculosas o infección oportunista
    Antecedente o evidencia actual de enfermedad infecciosa crónica o recurrente.
    Anticuerpos frente al VIH o hallazgo de positividad del VIH en la selección.
    Infección por Hepatitis B. Los sujetos deberán someterse a despistaje del virus de la hepatitis B.
    Seropositividad de anticuerpos frente al virus de la hepatitis C (HCV), salvo en caso de 2 resultados negativos de la prueba del RNA del HCV con 6 meses de separación antes de la selección y un tercer negativo en la selección.
    Erupción reciente por herpes en un solo dermatoma en los 4 últimos meses. Presentación en algún momento de herpes zóster en múltiples dermatomas o de zóster en sistema nervioso central.
    En los 2 meses previos a la primera dosis, infección grave u hospitalización por infección, o tto con antibióticos IV por infección.
    Antecedente o sospecha de lupus de origen medicamentoso.
    Deficiencia hereditaria del complemento o inmunodeficiencia variable combinada.
    Proteínas en orina >4g/día o cociente proteínas/creatinina que se estima equivalente a proteinuria >4g/día.
    Antecedente de síndrome antifosfolipídico catastrófico.
    Hipersensibilidad conocida a las inmunoglobulinas humanas.
    Enfermedad de carácter mayor o evidencia de estado clínico inestable, enfermedad de cualquier sistema orgánico o infección aguda o crónica activa.
    Cirugía mayor en el mes anterior a la selección, o ausencia de recuperación completa de la intervención, o programación de cirugía mayor durante el tiempo que el sujeto participe en el estudio o en el mes después de la última dosis del estudio.
    Receptor de trasplante de órgano.
    Uso semipermanente de peluca adherida que pueda interferir con la puntuación de la enfermedad cutánea.
    Problema de consumo de drogas o alcohol actual o en los 3 años previos.
    Presencia o antecedentes de neoplasia maligna en los 5 años anteriores a la selección. Nótese carcinoma de cérvix y cáncer de piel como excepciones.
    Antecedente de enfermedad linfoproliferativa, incluidos linfomas, o clínica sugerente de enfermedad linfoproliferativa.
    Uso de gamma globulina IV, aféresis o immunoadsorción en los 6 meses antes de la primera dosis y 4 después de la última.
    Haber recibido trasplante de células madre.
    Para el resto de criterios o más detalles, véase protocolo.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the proportion of subjects achieving an SRI-4 composite response at Week 52.
    El criterio principal de valoración es el porcentaje de sujetos que alcancen una respuesta compuesta SRI-4 (SLE Responder Index) en la Semana 52.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 52
    Semana 52
    E.5.2Secondary end point(s)
    1. Time to flare based on the proportion of subjects with a flare occurring at any time after the baseline visit through Week 52, with flare defined as either 1 or more new BILAG A or 2 or more new BILAG B domain scores
    2. The proportion of subjects with an SRI-4 composite response at Week 24
    3. The proportion of subjects achieving at least a 50% improvement in the number of joints with pain and signs of inflammation at Week 52 in subjects with at least 4 affected joints at baseline
    4. The proportion of subjects who achieve reduction in glucocorticoid dose by Week 40 and sustain that reduction through Week 52
    5. The proportion of subjects achieving at least a 50% improvement in the CLASI Activity Score at Week 52 in subjects with a CLASI Activity Score of 4 or greater at baseline
    6. The proportion of subjects with SRI-4 composite response at Week 52 in the subpopulation who achieved reduction in glucocorticoid dose by Week 40 and sustained that reduction through Week 52
    1. Tiempo hasta el brote, en función del porcentaje de sujetos que presenten un brote en cualquier momento desde la visita basal hasta la Semana 52, con la siguiente definición de brote: una o más puntuaciones de dominio BILAG (British Isles Lupus Assessment Group) A nueva o 2 o más puntuaciones de dominio BILAG B nuevas
    2. Porcentaje de sujetos con una respuesta completa SRI-4 en la Semana 24.
    3. Porcentaje de sujetos con al menos 4 articulaciones afectadas en el momento basal que logren una mejoría del 50%, como mínimo, en el número de articulaciones con dolor y signos de inflamación en la Semana 52.
    4. Porcentaje de sujetos que hayan logrado una reducción de la dosis de glucocorticoides en la Semana 40 y que mantengan dicha reducción hasta la Semana 52.
    5. Porcentaje de sujetos con una puntuación de actividad CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) igual o superior a 4 en el momento basal que logren una mejoría del 50%, como mínimo, en dicha puntuación de actividad CLASI en la Semana 52.
    6. Porcentaje de sujetos en tratamiento con glucocorticoides en el momento basal que hayan logrado una reducción de la dosis de glucocorticoides en la Semana 40, mantengan dicha reducción hasta la Semana 52 y hayan logrado una respuesta compuesta SRI-4 en la Semana 52.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1.Week 52
    2.Week 24
    3.Week 52
    4.Week 52
    5.Week 52
    6.Week 52
    1.Semana 52
    2.Semana 24
    3.Semana 52
    4.Semana 52
    5.Semana 52
    6.Semana 52
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    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 Yes
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA75
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Bulgaria
    China
    Colombia
    Ecuador
    Germany
    Hungary
    Japan
    Korea, Republic of
    Lithuania
    Peru
    Philippines
    Poland
    Romania
    Russian Federation
    Serbia
    South Africa
    Spain
    Taiwan
    Ukraine
    United States
    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
    UVUP
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 20
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 20
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 460
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 170
    F.4.2.2In the whole clinical trial 500
    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
    Ninguno
    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 Decision2018-06-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-04-11
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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