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    Summary
    EudraCT Number:2015-000400-26
    Sponsor's Protocol Code Number:201842
    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:2015-10-05
    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 number2015-000400-26
    A.3Full title of the trial
    A randomized, double blind (sponsor open), comparative, multicenter study to evaluate the safety and efficacy of subcutaneous belimumab (GSK1550188) and intravenous rituximab coadministration in subjects with primary Sjögren's syndrome.
    Estudio aleatorizado, doble ciego (abierto para el promotor), comparativo, multicéntrico para evaluar la seguridad y la eficacia de la coadministración de belimumab (GSK1550188) subcutáneo y rituximab intravenoso en sujetos con síndrome de Sjögren primario.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2, randomized, double blind, placebo controlled study to evaluate the safety and efficacy of belimumab and rituximab co-administration in subjects with primary Sjögren's syndrome
    Estudio fase II, aleatorizado, doble ciego, controlado con placebo para evaluar la seguridad y eficacia de la coadministración de belimumab y rituximab en sujetos con síndrome de Sjögren primario.
    A.4.1Sponsor's protocol code number201842
    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 SponsorGlaxoSmithKline, 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 supportGlaxoSmithKline R&D
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline
    B.5.2Functional name of contact pointCentro de Información
    B.5.3 Address:
    B.5.3.1Street AddressC/Severo Ochoa, 2
    B.5.3.2Town/ cityTres Cantos (Madrid)
    B.5.3.3Post code28760
    B.5.3.4CountrySpain
    B.5.4Telephone number+34902202700
    B.5.5Fax number+34918070479
    B.5.6E-mailes-ci@gsk.com
    D. IMP Identification
    D.IMP: 1
    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 MabThera (Rituximab)
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    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 nameMabThera (Rituximab)
    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 INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.3Other descriptive nameMABTHERA
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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 Benlysta (Belimumab)
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxo Group Ltd.
    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 nameBenlysta (Belimumab)
    D.3.4Pharmaceutical form
    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 INNBELIMUMAB
    D.3.9.1CAS number 356547-88-1
    D.3.9.2Current sponsor codeGSK1550188
    D.3.9.3Other descriptive nameHGS1006, LymphoStat-B, monoclonal anti-BLyS, LSB, BENLYSTA
    D.3.9.4EV Substance CodeSUB25607
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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 placeboConcentrate for solution for injection
    D.8.4Route of administration of the placeboIntravenous use
    D.8 Placebo: 2
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary Sjogrens disease
    Síndrome de Sjögren primario.
    E.1.1.1Medical condition in easily understood language
    Sjogren's Syndrome
    Síndrome de Sjögren
    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 18.0
    E.1.2Level PT
    E.1.2Classification code 10061664
    E.1.2Term Autoimmune disorder
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Safety and tolerability of anti-BLyS / anti-CD 20 coadministration therapy and anti-BLyS and anti-CD 20 monotherapies.
    Seguridad y tolerabilidad de la coadministración de anti-BLyS /anti-CD 20 y de las monoterapias con anti-BLyS y con anti-CD 20.
    E.2.2Secondary objectives of the trial
    -Clinical efficacy of anti-BLyS / anti-CD 20 co-administration therapy and anti-BLyS and anti-CD 20 monotherapies

    -Assessment of anti-BLyS / anti-CD 20 co-administration therapy and anti-BLyS and anti-CD 20
    monotherapies on tissue B-cells.
    - Eficacia clínica de la coadministración de anti-BLyS /anti-CD 20 y de las monoterapias con anti-BLyS y con anti-CD 20

    -Evaluación del tratamiento de la coadministración con anti-BLyS/anti- CD 20 y de las monoterapias con anti-BLyS y con anti-CD 20 sobre las células B
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    AGE
    1. Age >=18 years, at the time of signing the informed consent.

    TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
    2. Documented Primary Sjögren's Syndrome by American European Consensus Group criteria including:
    - either SS-A or SS-B positive.
    3. Baseline unstimulated salivary flow >0.0 mL/min or evidence of glandular reserve function (stimulated baseline salivary flow >0.05 mL/min).
    4. Symptomatic oral dryness (>=5/10 on subject completed Numeric Response Scale)
    5. Systemically active disease, ESSDAI >=5 points.

    SEX
    6. Male and female subjects; females of child bearing potential are eligible if using effective contraception:

    Female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotropin (hCG) test), not lactating, and at least one of the following conditions applies:

    a. Non-reproductive potential defined as:
    -Pre-menopausal females with one of the following:
    -Documented tubal ligation
    -Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
    -Hysterectomy
    -Documented Bilateral Oophorectomy

    - Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study; otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
    b. Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication up to Week 68 after Day 0.

    GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP)

    This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penilevaginal intercourse on a long term and persistent basis.

    -Contraceptive subdermal implant that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label
    -Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label
    -Oral Contraceptive, either combined or progestogen alone
    -Injectable progestogen
    -Contraceptive vaginal ring
    -Percutaneous contraceptive patches
    -Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject.
    -Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository).

    These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label.

    The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
    EDAD
    1. Edad >=18 años en el momento de la firma del consentimiento informado.
    TIPO DE SUJETO Y DIAGNÓSTICO QUE INCLUYA LA GRAVEDAD DE LA ENFERMEDAD
    2. Síndrome de Sjögren Primario documentado por los criterios del American European Consensus Group que incluyen: SS-A o SS-B positivo.
    3. Flujo salival no estimulado basal >0,0 mL/min o evidencia de función de reserva glandular (flujo salival basal estimulado >0,05 mL/min).
    4. Sequedad de boca sintomática (>=5/10 en la Escala de Respuesta Numérica completada por el sujeto)
    5. Enfermedad sistémica activa, ESSDAI >=5 puntos.
    SEXO
    6. Hombres y mujeres; las mujeres en edad fértil son elegibles si utilizan métodos anticonceptivos efectivos:
    Una mujer es elegible para participar si no está en periodo de gestación (confirmado por una prueba de gonadotropina coriónica humana (hCG) en orina negativa ni de lactancia, y cumple al menos una de las siguientes condiciones:
    a. No es fértil, definido como:
    - Mujeres premenopáusicas con una de las siguientes opciones:
    - Ligadura de trompas documentada
    - Procedimiento de oclusión tubárica histeroscópica documentada con subsiguiente confirmación de oclusión tubárica bilateral
    - Histerectomía
    - Ooforectomía bilateral documentada
    - Las mujeres postmenopáusicas se definen como aquellas con 12 meses de amenorrea espontánea [en los casos dudosos deben tener unos niveles en sangre de hormona estimulante del folículo (FSH) y estradiol consistentes con la menopausia (consultar los rangos de referencia del laboratorio)]. Las mujeres que estén recibiendo terapia de sustitución hormonal (TSH) y cuyo estado menopáusico sea dudoso tendrán que utilizar un método anticonceptivo altamente efectivo si desean continuar con su TSH durante el estudio; de lo contrario, deben interrumpir el TSH hasta que se pueda confirmar su estado posmenopáusico antes del reclutamiento en el estudio.
    b. Es fértil y está de acuerdo en utilizar una de las opciones que se citan en la Lista Modificada de GSK de Métodos Anticonceptivos Altamente Efectivos en Mujeres Fértiles (MF) desde 30 días antes de la primera dosis de medicación del estudio hasta la Semana 68 después del Día 0.
    Lista Modificada de GSK de Métodos Anticonceptivos Altamente Efectivos en Mujeres Fértiles (MF)
    Esta lista no se aplica a las MF con parejas del mismo sexo, cuando éste sea su estilo de vida preferido y habitual o en las pacientes que se abstengan de mantener, a largo plazo y de forma continua, relaciones sexuales con penetración vaginal.

    - Implante anticonceptivo subdérmico que cumpla los criterios de efectividad de los PNT, incluida una tasa de fracasos <1% anual, según se establece en la ficha técnica del producto
    - Dispositivo intrauterino o sistema intrauterino que cumpla los criterios de efectividad de los PNT, incluida una tasa de fracasos <1% anual, según se establece en la ficha técnica del producto
    - Anticonceptivo oral, combinado o progesterona sola
    - Progestágeno inyectable
    - Anillo vaginal anticonceptivo
    - Parches anticonceptivos percutáneos
    - Esterilización de la pareja sexual masculina con documentación de azoospermia antes de que la mujer entre en el estudio, y este varón debe ser la única pareja sexual de la mujer.
    - Preservativo combinado con un espermicida vaginal (espuma, gel, película, crema o supositorio).
    Estos métodos anticonceptivos permitidos sólo son efectivos cuando se utilizan de forma sistemática, correcta y de acuerdo con las especificaciones de la ficha técnica.

    El investigador es el responsable de garantizar que los sujetos saben cómo utilizar correctamente estos métodos anticonceptivos.
    CONSENTIMIENTO INFORMADO
    7. Capacidad para entender y cumplir los procedimientos del protocolo y proporcionar consentimiento informado.
    E.4Principal exclusion criteria
    CONCURRENT CONDITIONS/MEDICAL HISTORY
    1. Diagnosis of secondary Sjögren's syndrome.
    2. Active life-threatening or organ-threatening complications of SS disease at the time of screening based on treating physician evaluation including but not restricted to (a) vasculitis with renal, digestive, cardiac, pulmonary or CNS involvement characterized as severe, (b) active CNS or PNS involvement requiring high dose steroids, (c) severe renal involvement defined by objective measures, (d) lymphoma.
    3. History of major organ transplant
    4. History of malignancy within past 5 years [with the exception of adequately treated:
    (a) cervical carcinoma Stage 1B or less, (b) non-invasive basal cell and squamous cell skin carcinoma].
    5. History of infection requiring long term systemic therapy including: (a) history of positive HIV serology, (b) positive serology for Hepatitis C (HCV), (c) positive
    serology for Hepatitis B (HB), defined as: (i) HB surface antigen positive (HBsAg+) OR (ii) HB core antibody positive (HBcAb+).
    6. Previous serious opportunistic or atypical infections or hospitalization for treatment of infection within 364 days of Day 0 or use of parenteral (IV or IM) antibacterials, antivirals, anti-fungals, or anti-parasitic agents within 364 days of prior to Day 0.
    7. Patients in a severely immunocompromised state.
    8. History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.
    9. History of significant medical illness which in the opinion of the investigator would interfere with the study procedures and / or assessments - including but not limited to IgG4 disease or prior head or neck irradiation.
    10. Severe heart failure or other severe, uncontrolled cardiac disease.
    11. Tuberculosis (TB), defined as: (a) prior history of TB infection, (b) suspicion of TB infection or (c) current TB infection
    12. At risk of suicide, as indicated by a lifetime history of attempted suicide or significant suicidal ideation over the 6 months prior to the screening visit; or, if in
    the Investigator's judgment, the subject is at risk for a suicide attempt.
    13. Neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML) - not otherwise explained - or confirmed PML.
    14. Electrocardiogram (ECG) showing a clinically significant abnormality at Screening or showing an average QTcB or QTcF interval ?450 msec over 3 consecutive ECGs
    15. ALT >2xULN and bilirubin >1.5xULN
    16. Current or chronic history of liver disease, or known hepatic or biliary abnormalities.

    CONCOMITANT MEDICATIONS
    17. Use of systemic immunosuppressive or immunomodulatory agents including
    methotrexate, azathioprine, leflunomide, mycophenolate, mizoribine, calcineurin inhibitors, sirolimus, 6-mercaptopurine, or thalidomide) within 60 days prior to Day 0.
    18. Have received cyclophosphamide within 180 days prior to Day 0.
    19. Have received anti-BLyS, anti-CD 20, anti-CD22 or anti-CD52 or any other B-cell depleting agent within 364 days prior to Day 0.
    20. Have received abatacept or any biologic agent within 180 day prior to Day 0.
    21. Have received IVIG or plasmapheresis within 90 days prior to Day 0.
    22. Have received oral steroid >10 mg prednisone equivalent/day within 30 days prior to Day 0 or oral steroid >20 mg prednisone equivalent / day for a minimum of two consecutive weeks within 60 days prior to Day 0. Have received parenteral steroid within 60 days prior to Day 0.
    23. Have received a live vaccine within 30 days of Day 0.
    24. Current participation in any other interventional trial.
    25. Planned blood donation during the treatment and follow up periods of the study.

    RELEVANT HABITS
    26. Subjects who are unable or unwilling to administer, or to have a caregiver administer subcutaneous injections.
    27. Drug or alcohol abuse or dependence.

    CONTRAINDICATIONS
    28. History of hypersensitivity to belimumab and/or rituximab or known to have titers of human anti-mouse antibody or human anti-chimeric antibody or history of
    hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.

    DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
    29. Have an IgA deficiency (IgA level <10 mg/dL).
    30. Any of the following screening laboratory values:
    -White blood cells (WBC) <2 x 109/L
    -Neutrophils <1.5 x 109/L
    -Circulating IgG or IgM levels <lower limit of normal (according to central laboratory range)
    - Aspartate aminotransferase (AST) >2.0 times the upper limit of normal
    - Alkaline phosphatase (ALP) >1.5 times the upper limit of normal
    - Bilirubin >1.5 times the upper limit of normal
    - CD4 count <400 cells/mm3
    - CD8 count <150 cells/mm3
    - CD19+ B-lymphocyte counts <0.1 x 109/L
    1. Diagnóstico de síndrome de Sjögren secundario.
    2. Complicaciones del SS que amenazan un órgano o la vida en el momento de la selección, basadas en la evaluación del médico, incluidas pero no limitadas a (a) vasculitis con afectación renal, digestiva, cardiaca, pulmonar o del SNC clasificada como grave, (b) afectación activa del SNC o SNP que requiera la administración de dosis altas de esteroides, (c) afectación renal grave definida por medidas objetivas, (d) linfoma.
    3. Historia de trasplante de órgano mayor (incluido el trasplante de células madre hematopoyéticas)
    4. Historia de neoplasia maligna en los últimos 5 años [excepto los casos adecuadamente tratados de (a) carcinoma de cuello uterino de estadio 1B o inferior, (b) carcinoma cutáneo de células escamosas o de células basales no invasivo].
    5. Historia de infección que requiere terapia sistémica prolongada, incluidas: (a) historia de serología VIH positiva, (b) serología de hepatitis C o B positivas.
    6. Infecciones oportunistas o atípicas graves previas u hospitalización para tratamiento de una infección o utilización de antibacterianos parenterales (IM o IV), antivirales, antifúngicos o antiparasitarios en los 364 días anteriores al Día 0.
    7. Pacientes con un estado de inmunodepresión grave.
    8. Historia de reacción anafiláctica a la administración parenteral de contrastes radiológicos, proteínas humanas o murinas o anticuerpos monoclonales.
    9. Historia de enfermedad (o intervención quirúrgica programada) significativa que, a juicio del investigador, interferiría con los procedimientos o evaluaciones del estudio.
    10. Insuficiencia cardiaca grave u otra cardiopatía grave no controlada.
    11. Tuberculosis (TB), definida como: (a) historia previa de TB, (b) sospecha de TB o (c) TB actual.
    12. Riesgo de suicidio, indicado por antecedentes de intento de suicidio o ideas suicidas significativas durante los 6 meses anteriores a la visita de selección; o, si a juicio del investigador, el sujeto tiene riesgo de intento de suicidio.
    13. Hallazgos neurológicos consistentes con Leucoencefalopatía Multifocal Progresiva (LMP) - no explicados por otras causas - o LMP confirmada.
    14. Electrocardiograma (ECG) de muestre una anomalía con significación clínica en la Selección o muestre un intervalo QTcB o QTcF >=450 mseg (>=480 mseg en los sujetos con bloqueo de rama) en 3 ECGs consecutivos.
    15. ALT >2xLSN y bilirrubina >1,5xLSN (la bilirrubina aislada >1,5xLSN es aceptable si, al hacer el análisis fraccionado, la bilirrubina directa es <35%).
    16. Historia actual o crónica de hepatopatía, o anomalías hepáticas o biliares conocidas (excepto el síndrome de Gilbert o los cálculos de vesícula asintomáticos)
    17. Empleo de fármacos inmunosupresores o inmunomoduladores sistémicos en los 60 días anteriores al Día 0.
    18. Haber recibido ciclofosfamida en los 180 días anteriores al Día 0.
    19. Haber recibido anti-BLyS, anti-CD20, anti-CD22 o anti-CD52 o cualquier otro fármaco reductor de las células B en los 364 días anteriores al Día 0.
    20. Haber recibido abatacept o cualquier fármaco biológico en los 180 días anteriores al Día 0 (excepto denosumab).
    21. Haber recibido IGIV o plasmaféresis en los 90 días anteriores al Día 0.
    22. Haber recibido esteroides orales a dosis >10 mg de equivalente de prednisona/día en los 30 días anteriores al Día 0 o esteroides orales a dosis >20 mg de equivalente de prednisona/día durante un mínimo de dos semanas consecutivas en los 60 días anteriores al Día 0. Haber recibido esteroides parenterales en los 60 días anteriores al Día 0.
    23. Haber recibido una vacuna viva en los 30 días anteriores al Día 0.
    24. Participación actual en otro ensayo de intervención.
    25. Tener previsto donar sangre durante los periodos de tratamiento y seguimiento del estudio.
    26. Sujetos incapacitados o que no estén dispuestos a administrarse las inyecciones subcutáneas.
    27. Abuso o dependencia de alcohol o drogas.
    28. Historia de hipersensibilidad a belimumab, rituximab o ambos, o títulos conocidos de anticuerpos anti-ratón humanos o anticuerpos anti-quiméricos humanos, o historia de reacciones de hipersensibilidad con otros anticuerpos monoclonales diagnósticos o terapéuticos.
    29. Deficiencia de IgA (Nivel de IgA <10 mg/dL).
    30. Cualquiera de los siguientes valores de laboratorio en la selección:
    - Leucocitos <2 x 10^9/L
    - Neutrófilos <1,5 x 10^9/L
    - Niveles de IgG o IgM circulantes <límite inferior normal
    - Aspartato aminotransferasa (AST) >2,0 veces el límite superior normal
    - Fosfatasa alcalina (ALP) >1,5 veces el límite superior normal
    - Bilirrubina >1,5 veces el límite superior normal
    - Recuento de CD4 <400 células/mm3
    - Recuento de CD8 <150 células/mm3
    - Recuento de linfocitos B CD19+ <0,1 x 10^9/L
    E.5 End points
    E.5.1Primary end point(s)
    Safety and tolerability
    Seguridad y tolerabilidad
    E.5.1.1Timepoint(s) of evaluation of this end point
    Weeks 24 and 52
    Semanas 24 y 52
    E.5.2Secondary end point(s)
    ESSDAI score; stimulated salivary flow; oral dryness numeric response scale; B cell quantification within the salivary gland
    Puntuación ESSDAI; Flujo salival estimulado; Escala de respuesta numérica de la sequedad de boca, Cuantificación de células B en la biopsia de las glándulas salivales.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 24 and 52
    Semanas 24 y 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 No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Transcriptomic and proteonomic analyses.
    Análisis de transcriptómica y proteómica.
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 Yes
    E.8.1.7.1Other trial design description
    Sponsor unblinded
    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 trial4
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA26
    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
    Canada
    France
    Germany
    Italy
    Netherlands
    Norway
    Spain
    Sweden
    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
    Última visita del último paciente.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    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: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 120
    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)
    Subjects will not receive any additional treatment from GSK after completion of the
    study.

    The investigator is responsible for ensuring that consideration has been given to the poststudy care of the subject's medical condition, whether or not GSK is providing specific post-study treatment.
    Los sujetos no recibirán ningún tratamiento adicional de GSK tras completar el estudio.

    El investigador es el responsable de garantizar que se han tenido en cuenta los cuidados del sujeto después del estudio, independientemente de que GSK proporcione o no un tratamiento específico.
    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 Decision2015-11-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-11-05
    P. End of Trial
    P.End of Trial StatusOngoing
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