Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   36401   clinical trials with a EudraCT protocol, of which   5997   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2016-003050-32
    Sponsor's Protocol Code Number:205646
    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:2017-12-01
    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 number2016-003050-32
    A.3Full title of the trial
    A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-
    Controlled, 104-Week Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination with Rituximab to Adult Subjects with Systemic Lupus Erythematosus (SLE).
    Estudio en fase 3, multicéntrico, aleatorizado, doble ciego,
    controlado con placebo y de 104 semanas de duración para evaluar la eficacia y la seguridad de belimumab administrado en combinación con rituximab en adultos con lupus eritematoso sistémico (LES).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Study to Evaluate the Efficacy and Safety of Belimumab
    Administered in Combination with Rituximab to Adult Subjects with Systemic Lupus Erythematosus (SLE) – BLISS-BELIEVE
    Estudio en fase 3 para evaluar la eficacia y la seguridad de
    belimumab administrado en combinación con rituximab en adultos con lupus eritematoso sistémico (LES) – BLISS - BELIEVE
    A.4.1Sponsor's protocol code number205646
    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 LLC
    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 (P.T.M.)
    B.5.3.2Town/ cityTres Cantos (Madrid)
    B.5.3.3Post code28760
    B.5.3.4CountrySpain
    B.5.4Telephone number34902202700
    B.5.5Fax number34918070479
    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.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 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 Solution for injection in pre-filled pen
    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) No
    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 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 (SLE) or Lupus
    lupus eritematoso sistémico (LES)
    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
    To evaluate the efficacy of belimumab and a single cycle of rituximab administered in a combination regimen to adult participants with SLE.
    Evaluar la eficacia de belimumab y un solo ciclo de rituximab administrados en una pauta de combinación en adultos con LES.
    E.2.2Secondary objectives of the trial
    - To assess the safety and tolerability of belimumab and a single cycle of rituximab administered in a combination regimen to adult participants with SLE.
    - To assess the impact of belimumab and a single cycle of rituximab administered in a combination regimen to adult participants with SLE on PROs.
    - Evaluar la seguridad y tolerabilidad de belimumab y un solo ciclo de rituximab administrados en una pauta de combinación en adultos con LES.
    - Evaluar el efecto en los RCP de belimumab y un solo ciclo de rituximab administrados en una pauta de combinación a adultos con LES.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Participant must be ≥ 18 years of age at the time of signing the informed consent.
    2. Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) criteria.
    3. Have a screening SLEDAI-2K score ≥6 (serological activity, i.e., anti-double stranded deoxyribonucleic acid [dsDNA]) positivity and/or hypocomplementemia, is scored in the SLEDAI-2K).
    4. Have unequivocally positive autoantibody test results defined as an anti-nuclear (ANA) titer ≥ 1:80 and/or a positive anti-dsDNA ( ≥30 IU/mL) serum antibody test from 2 independent time points as follows:
    Positive test results from 2 independent time points within the study screening period. Screening results must be based on the study's central laboratory results
    OR
    One positive historical test result and 1 positive test result during the screening period.
    NOTE: Historical documentation of a positive test of ANA (e.g., ANA by HEp-2 titer) and anti-dsDNA (e.g., anti-dsDNA by Farr assay) that must include the
    date and type of the test, the name of the testing laboratory, numerical reference range, and a key that explains values provided as positive vs. negative. Only unequivocally positive values as defined in the laboratory's reference range are acceptable; borderline values will not be accepted.
    5. Are on a stable SLE treatment regimen consisting of any of the following medications (alone or in combination) for a period of at least 30 days prior to Day 1 (i.e., day of first dose of study treatment) with the exception that switching one agent for another of the same class for tolerability or availability reasons, which will be allowed within 30 days of Day 1.
    ∙Corticosteroids (prednisone or prednisone equivalent)
    ∙For those subjects on alternating daily doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose.
    ∙Any immunosuppressant or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (e.g. tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6- mercaptopurine, mizoribine, or thalidomide.
    ∙Anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine).
    ∙Non-steroidal anti-inflammatory drugs (NSAIDs).
    NOTES: Corticosteroids may be added as a new medication or their doses adjusted up to 30 days prior to Day 1.
    New SLE therapy other than corticosteroids must not be added within 60 days prior to Day 1.
    6. Male and/or female
    A female participant is eligible to participate if she is not pregnant (see Appendix 3 of the study protocol), not breastfeeding, and at least one of the following conditions applies:
    (i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 (of the study protocol)
    OR
    (ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 (of the study protocol) during the treatment period and for at least 16 weeks after the last dose of belimumab, or at least 12 months after the last dose of rituximab or rituximab placebo, whichever is later.
    7. Capable of giving signed informed consent as described in Appendix 4 (of the study protocol) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    1. El paciente deberá tener de 18 o más años de edad en el momento de firmar el consentimiento informado.
    2. Tengan un diagnóstico clínico de LES según los criterios del American College of Rheumatology (ACR).
    3. Tengan una puntuación ≥ 6 en SLEDAI 2K (la actividad serológica, es decir, positividad de anti-ácido desoxirribonucleico bicatenario [ADNbc] o hipocomplementemia, se puntúa en SLEDAI 2K).
    4. Tengan resultados inequívocamente positivos en el análisis de autoanticuerpos, definidos como un título de anticuerpos antinucleares (ANA) ≥ 1:80 o un análisis positivo de anticuerpos anti-ADNbc (≥ 30 UI/ml) en suero en dos puntos temporales independientes, tal como sigue:
    - Resultados positivos en el análisis en dos puntos temporales independientes en el periodo de selección del estudio. Los resultados de la selección deben basarse en los resultados del laboratorio central del estudio
    O
    - Un resultado histórico positivo en los análisis y un resultado positivo en los análisis durante el periodo de selección.
    NOTA: La documentación histórica de un análisis positivo de ANA (p. ej., ANA según el título de HEp-2) y anti-ADNbc (p. ej., anti-ADNbc mediante el análisis de Farr) debe incluir la fecha y el tipo del análisis, el nombre del laboratorio que realice el análisis, el intervalo de referencia y una clave que explique los valores positivos y negativos. Solo son aceptables valores inequívocamente positivos tal como se definan en el intervalo de referencia del laboratorio; no se aceptarán valores en el límite.
    5. Pacientes que reciban una pauta de tratamiento estable para el LES, consistente en cualquiera de los medicamentos siguientes (solos o en combinación) durante al menos 30 días antes del día 1 (es decir, el día de la primera dosis del tratamiento del estudio), con la excepción de la sustitución de un fármaco por otro de la misma clase por motivos de tolerabilidad o disponibilidad, lo que se permitirá en los 30 días antes del día 1.
    - Corticosteroides (prednisona o equivalente de prednisona)
    - En los pacientes que reciban dosis diarias alternativas de esteroides hay que usar el promedio de dos dosis diarias para calcular la dosis diaria media de esteroides.
    - Cualquier inmunodepresor o inmunomodulador, como metotrexato, azatioprina, leflunomida, micofenolato (incluidos micofenolato mofetilo, clorhidrato de micofenolato mofetilo y micofenolato sódico), inhibidores de la calcineurina (p. ej., tacrolimús, ciclosporina), sirolimús, ciclofosfamida oral, 6-mercaptopurina, mizoribina o talidomida.
    - Antipalúdicos (p. ej., hidroxicloroquina, cloroquina, quinacrina).
    - Antiinflamatorios no esteroideos (AINE).
    NOTAS: Se pueden añadir corticosteroides como nuevo medicamento o se pueden ajustar sus dosis hasta 30 días antes del día 1.
    No se debe añadir ningún tratamiento nuevo para el LES distinto de los corticosteroides en los 60 días previos al día 1.
    6. Varones y mujeres
    Las mujeres podrán participar si no están embarazadas (véase el Apéndice 3 del Protocolo) o en periodo de lactancia y se aplica al menos una de las condiciones siguientes:
    (i) No son mujeres en edad fértil (MEF) como se define en el Apéndice 3 del Protocolo.
    O
    (ii) Es una MEF que se compromete a adoptar las medidas anticonceptivas del Apéndice 3 durante el período de tratamiento y durante al menos 16 semanas después de la última dosis de belimumab o al menos 12 meses después de la última dosis de rituximab o rituximab-placebo, lo que suceda más tarde.
    7. Capacidad de otorgar el consentimiento informado firmado, tal como se describe en el Apéndice 4, lo que incluye el cumplimiento de los requisitos y restricciones mencionados en el DCI y en el protocolo.
    E.4Principal exclusion criteria
    1. Symptomatic herpes zoster within 3 months prior to screening.
    2. Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior, anterior, and lateral), and TB testing
    3. Significant allergies to humanized monoclonal antibodies.
    4. Clinically significant multiple or severe drug allergies and/or history of hypersensitivity to belimumab and/or rituximab or known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.
    5. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
    6. Alanine transferase (ALT) >2x upper limit of normal (ULN).
    7. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
    8. IgA deficiency (IgA level < 10 mg/dL).
    9. IgG < 250 mg/dL.
    10. Neutrophils < 1.5 x 10 to the power of 9
    11. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
    12. Severe heart failure (New York Heart Association Class IV) or other severe, uncontrolled cardiac disease.
    13. QTc >450 msec or QTc >480 msec in participants with bundle branch block.
    14. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant.
    15. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.
    16. Have an acute or chronic infection requiring management as follows:
    Currently on any suppressive therapy for a chronic infection
    ∙Hospitalization for treatment of infection within 60 days of Day 1.
    ∙Have had infection requiring treatment with parenteral (IV or IM) antibiotics within 60 days of Day 1. Prophylactic anti-infective treatment is allowed.
    17. Have severe lupus kidney disease (defined by proteinuria >6 g/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine >2.5 mg/dL), or have severe active nephritis requiring induction therapy not permitted by protocol, or have required hemodialysis or high dose prednisone or equivalent (>100 mg/day) within 90 days of Day 1.
    18. Have severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA), cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 1.
    19. Have a planned surgical procedure, laboratory abnormality, or condition that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
    20. Have evidence of serious suicide risk, including any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 2 months or who, in the investigator's opinion, pose a significant suicide risk.
    21. Have a history of an anaphylaxis reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies.
    22. Live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the screening period or during the study.
    23. Have received any of the following within 364 days of Day 1:
    ∙Belimumab.
    ∙Rituximab.
    ∙Abatacept.
    ∙Any B cell targeted therapy anti-Interferon alpha agents or anti-BLyS other than belimumab).
    ∙A biologic investigational agent other than B cell targeted therapy
    24. Have required 3 or more courses of systemic corticosteroids within 364 days of Day 1. (Topical or inhaled steroids are permitted.)
    25. Have received any of the following within 90 days of Day 1:
    ∙ Anti-TNF therapy
    ∙ Interleukin-1 receptor antagonist
    ∙ Intravenous immunoglobulin
    ∙ High dose prednisone or equivalent
    ∙ Plasmapheresis
    26. Have received any of the following within 60 days of Day 1:
    ∙A non-biologic investigational agent
    ∙Intravenous (IV) cyclophosphamide
    ∙Any steroid injection
    27. Positive immunodeficiency virus (HIV) antibody test.
    28. Positive serology for Hepatitis B, defined as (i) HB surface antigen positive (HBsAg+) OR (ii) HB core antibody positive (HBcAb+).
    29. Positive Hepatitis C (HCV) antibody test.
    30. Have current drug or alcohol dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 1.
    31. Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
    32. Unable to administer study treatment (belimumab) by SC injection and has no other reliable resource to administer the injection.
    1. Herpes zóster sintomático en los 3 meses previos a la selección.
    2. Signos de TB activa o latente, documentados mediante la historia clínica y la exploración física, las radiografías de tórax (posterior, anterior y lateral) y el análisis de la TB.
    3. Alergias significativas a anticuerpos monoclonales humanizados.
    4. Alergias múltiples clínicamente significativas o intensas a la medicación o antecedentes de hipersensibilidad a belimumab o rituximab o títulos de anticuerpos antirratón humanos o antecedentes de reacciones de hipersensibilidad a otros anticuerpos monoclonales diagnósticos o terapéuticos.
    5. Linfoma, leucemia o cualquier neoplasia maligna en los últimos 5 años, salvo carcinomas basocelulares o espinocelulares de la piel que se hayan resecado sin signos de enfermedad metastásica durante 3 años.
    6. Alanina aminotransferasa (ALT) >2 x límite superior de la normalidad (LSN).
    7. Bilirrubina >1,5 x LSN (un valor aislado de bilirrubina > 1,5 x LSN es aceptable si la bilirrubina está fraccionada y la bilirrubina directa es <35%).
    8. Deficiencia de IgA (concentración de IgA <10 mg/dl).
    9. IgG <250 mg/dl.
    10. Neutrófilos <1,5x109.
    11. Enfermedad hepática o biliar inestable actual conforme a la evaluación del investigador, definida por la presencia de ascitis, encefalopatía, coagulopatía, hipoalbuminemia, varices esofágicas o gástricas, ictericia persistente o cirrosis.
    12. Insuficiencia cardíaca grave (clase IV de la NYHA) u otra cardiopatía no controlada grave.
    13. QTc >450 ms o QTc >480 ms en los pacientes con bloqueo de rama.
    14. Antecedentes de trasplante de órgano importante o trasplante de médula/células progenitoras hematopoyéticas.
    15. Signos clínicos de enfermedades agudas o crónicas importantes inestables o no controladas no debidas al LES que, en opinión del investigador principal, puedan confundir los resultados del estudio o suponer un riesgo indebido para el paciente.
    16. Infección aguda o crónica con necesidad de tratamiento, tal como sigue:
    - Tratamiento supresor en la actualidad para una infección crónica.
    - Hospitalización para tratamiento de una infección en los 60 días previos al día 1.
    - Infección con necesidad de tratamiento con antibióticos por vía parenteral (IV o IM) en los 60 días previos al día 1. Se permitirá el tratamiento antiinfeccioso profiláctico.
    17. Nefropatía lúpica grave (definida por proteinuria > 6 g/24 horas o equivalente empleando el cociente proteínas/creatinina en una muestra puntual de orina, o creatinina sérica >2,5 mg/dl) o nefritis activa grave con necesidad de un tratamiento de inducción no permitido por el protocolo o necesidad de hemodiálisis o de prednisona en dosis altas o equivalente (> 100 mg/día) en los 90 días previos al día 1.
    18. Lupus activo grave en el sistema nervioso central (SNC) (con crisis convulsivas, psicosis, síndrome cerebral orgánico, accidente cerebrovascular (ACV), cerebritis o vasculitis en el SNC) con necesidad de intervención terapéutica en los 60 días previos al día 1.
    19. Procedimiento quirúrgico programado, alteración analítica o situación que, en opinión del investigador principal, impidan que el paciente sea adecuado para el estudio.
    20. Indicios de riesgo de suicidio grave, con antecedentes de comportamiento suicida en los 6 últimos seis meses o cualquier ideación suicida de tipo 4 o 5 de la C-SSRS en los últimos 2 meses o que, en opinión del investigador, suponga un riesgo importante de suicidio.
    21. Presentar antecedentes de una reacción anafiláctica a la administración parenteral de agentes de contraste, proteínas humanas o murinas o anticuerpos monoclonales.
    22. Vacunación con vacunas vivas en el mes previo a la selección o plan para recibir tales vacunas durante el periodo de selección o durante el estudio.
    23. Tratamiento con cualquiera de lo siguiente en los 364 días previos al día 1: Belimumab; Rituximab; Abatacept; Cualquier tratamiento dirigido contra los linfocitos B y fármacos anti-interferón alfa u otros anti-BLyS diferentes de belimumab; Medicamento experimental biológico que no sea un tratamiento dirigido contra los linfocitos B.
    24. Necesidad de 3 o más ciclos de corticosteroides sistémicos en los 364 días previos al día 1. (Están permitidos los esteroides tópicos o inhalados.)
    25. Tratamiento con cualquiera de lo siguiente en los 90 días previos al día 1:
    -Tratamiento anti-TNF
    -Antagonista de los receptores de la interleucina 1
    -Inmunoglobulina intravenosa
    -Prednisona en dosis altas o equivalente
    -Plasmaféresis.
    26. Tratamiento con cualquiera de lo siguiente en los 60 días previos al día 1:
    -Medicamento experimental no biológico
    -Ciclofosfamida intravenosa
    -Cualquier inyección de esteroides
    27.Positividad del análisis de los anticuerpos contra el VIH.
    Ver Sección 6.2 del Protocolo para una lista completa de los Criterios de Exclusión.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of participants with a state of disease control defined as a SLEDAI- 2K score ≤2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of ≤5mg/day at Week 52. (Serological activity, i.e., anti-dsDNA positivity and/or hypocomplementemia, is scored in the SLEDAI-2K endpoint.)
    Porcentaje de pacientes con un estado de control de la enfermedad definido como una puntuación ≤ 2 en el Índice de actividad del lupus eritematoso sistémico (SLEDAI)-2K, conseguido sin inmunodepresores y con corticosteroides en una dosis equivalente de prednisona de ≤5 mg/día 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)
    Proportion of participants with a state of clinical remission defined as a Clinical
    SLEDAI-2K score =0, achieved without immuno-suppressants and with
    corticosteroids at a prednisone equivalent dose of 0 mg/day at Week 64. (Serological activity score, i.e., anti-dsDNA positivity and/or hypocomplementemia, is excluded from the Clinical SLEDAI-2K endpoint.)
    Proportion of participants with a state of disease control defined as a SLEDAI-2K
    score ≤2, achieved without immunosuppressants and withcorticosteroids at a prednisone equivalent dose of ≤5 mg/day at Week 104.
    - Porcentaje de pacientes con un estado de remisión clínica definido como una puntuación = 0 en SLEDAI 2K clínico, conseguido sin inmunodepresores y con corticosteroides en una dosis equivalente de prednisona de 0 mg/día en la semana 64. (La puntuación de actividad serológica, es decir, positividad de anti-ADNbc o hipocomplementemia, está excluida del criterio de valoración de SLEDAI 2K clínico.)
    - Porcentaje de pacientes con un estado de control de la enfermedad definido como una puntuación ≤ 2 en SLEDAI 2K, conseguido sin inmunodepresores y con corticosteroides en una dosis equivalente de prednisona de ≤5 mg/día en la semana 104.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Semana 64, Semana 104
    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 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 No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Brazil
    Canada
    Korea, Republic of
    Mexico
    Russian Federation
    South Africa
    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
    Última visita del último paciente.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days3
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days3
    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: 195
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 35
    F.4.2.2In the whole clinical trial 200
    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)
    At the end of the study, participants who wish to continue treatment with belimumab may do so by being prescribed commercially available belimumab.
    Al finalizar el estudio, lo pacientes que lo deseen podrán continuar el tratamiento con belimumab recibiendo el belimumab comercializado.
    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 Decision2017-12-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-11-24
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA