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    Summary
    EudraCT Number:2016-003328-22
    Sponsor's Protocol Code Number:56022473MDS2002
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Temporarily Halted
    Date on which this record was first entered in the EudraCT database:2017-04-21
    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 number2016-003328-22
    A.3Full title of the trial
    A Phase 2 Proof-of-Concept Study to Separately Evaluate the Activity of Talacotuzumab
    (JNJ-56022473) or Daratumumab in Transfusion-Dependent Subjects with Low or
    Intermediate-1 Risk Myelodysplastic Syndromes (MDS) who are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
    Estudio Fase 2, prueba de concepto, para evaluar de forma separada la actividad de Talacotuzumab (JNJ-56022473) o Daratumumab en sujetos con Síndrome Mielodisplásico (SMD) de riesgo bajo o intermedio-1 dependientes de transfusiones en recaída o refractarios al tratamiento con Agentes Estimulantes de la Eritropoyesis (AEE).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Proof-of Concept Study to Separately Study Talacotuzumab or Daratumumab in Low-Risk Intermediate-1 Risk Myelodysplastic Syndromes (MDS) patients
    Estudio prueba de concepto para estudiar de forma separada Talacotuzumab o Daratumumab en pacientes con Síndrome Mielodisplásico (SMD) de riesgo bajo o intermedio-1
    A.4.1Sponsor's protocol code number56022473MDS2002
    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, LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag S.A.
    B.5.2Functional name of contact pointGlobal Clinical Operations Spain
    B.5.3 Address:
    B.5.3.1Street AddressPaseo de las Doce Estrellas 5-7
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28042
    B.5.3.4CountrySpain
    B.5.4Telephone number+3491722 8100
    B.5.5Fax number+3491722 8628
    B.5.6E-mailagonza45@its.jnj.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTalacotuzumab
    D.3.2Product code JNJ-56022473
    D.3.4Pharmaceutical form Powder for 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 INNTalacotuzumab
    D.3.9.2Current sponsor codeJNJ-56022473
    D.3.9.4EV Substance CodeSUB176319
    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) 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 darzalex
    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 nameDaratumumab
    D.3.2Product code Hu-Max-CD38
    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 INNDARATUMUMAB
    D.3.9.1CAS number 945721-28-8
    D.3.9.2Current sponsor codeJNJ-54767414 (Daratumumab)
    D.3.9.3Other descriptive nameHUMAX-CD38
    D.3.9.4EV Substance CodeSUB175772
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Yes
    D.3.11.13.1Other medicinal product typehuman monoclonal antibody
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Transfusion-Dependent Subjects with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) who are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
    Sujetos con Síndrome Mielodisplásico (SMD) de riesgo bajo o intermedio-1 dependientes de transfusiones en recaída o refractarios al tratamiento con Agentes Estimulantes de la Eritropoyesis (AEE).
    E.1.1.1Medical condition in easily understood language
    Myelodysplastic Syndromes (MDS)
    Síndrome Mielodisplásico (SMD)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level LLT
    E.1.2Classification code 10028534
    E.1.2Term Myelodysplastic syndrome NOS
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to evaluate the efficacy (transfusion independence [TI]) of talacotuzumab (JNJ-56022473) or daratumumab in transfusion-dependent subjects with low or intermediate-1 risk MDS whose disease has relapsed during treatment with or is refractory to ESAs.
    El objetivo principal del estudio es evaluar la eficacia (independencia de transfusiones [IT]) de talacotuzumab (JNJ-56022473) o daratumumab sujetos con SMD de riesgo bajo o intermedio-1 dependientes de transfusiones cuya enfermedad ha recaído o es refractaria al tratamiento con Agentes Estimulantes de la Eritropoyesis
    E.2.2Secondary objectives of the trial
    - To evaluate the safety of talacotuzumab or daratumumab in the study population
    - To evaluate the clinical benefit of talacotuzumab and daratumumab in this study population through:
    - Time to TI and duration of TI
    - Rate of HI, CR, and PR
    - Overall survival (OS)
    - Progression to AML
    - Rate and amount of supportive care, including transfusions and myeloid growth factors
    - To characterize the PK of talacotuzumab and daratumumab in the study population
    - To evaluate the immunogenicity of talacotuzumab and daratumumab in subjects with MDS
    Evaluar la Seguridad de talacotuzumab o daratumumab en la población de estudio
    Evaluar el beneficio clinico de talacotuzumab o daratumumab en la población de estudio
    Tiempo a la IT y duración de la IT
    Tasa de mejora hematológica, RC y RP
    Supervivencia global
    Progresión a LMA
    Tasa y cantidad de cuidado de soporte, incluyendo transfusiones y factores de crecimiento mieloides.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. 18 years of age
    2. MDS according to World Health Organization criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to first dose. A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be approved by the sponsor.
    3. IPSS low risk or intermediate-1 risk MDS
    4. RBC transfusion dependent
    - Received at least 4 units of RBCs over any 8 consecutive weeks during the 16 weeks prior to randomization-Pretransfusion Hb must have been ≤9.0 g/dL
    Source documentation for transfusions verified by the sponsor.
    5. Relapsed/refractory to ESA treatment; the sponsor must verify this diagnosis as defined by meeting any of the criteria below:
    - Received at least 8 weeks of treatment with a minimum weekly dose of epoetin alfa 40,000 U, epoetin beta 30,000 U or darbepoetin alfa 150 mcg (or equivalent
    agent/dose) without having achieved a Hb rise ≥1.5 g/dL or decreased RBC
    transfusion requirement by at least 4 units over 8 weeks
    - Transfusion dependence or reduction in Hb by ≥1.5 g/dL after hematologic
    improvement, in the absence of another explanation;
    - Endogenous serum EPO level >500 mU/mL
    Source documentation for failure of ESA treatment verified by the sponsor
    6. Adequate iron stores, defined as transferrin saturation greater than 20% and serum ferritin greater than 400 ng/mL, measured within the screening period, or adequate iron stores as demonstrated by recent (within 12 weeks prior to first dose) bone marrow examination with iron stain.
    7. ECOG performance status 0, 1 or 2
    8. Hematology laboratory test values within the following limits:
    - ANC ≥1.0 x 10 to the 9th/L (ie, ≥1,000/mm3) independent of growth factor support. For the screening ANC to be considered growth factor independent, a 7-day period after stopping the growth factor should be observed, or 7 half-lives of growth factor used, whichever is longer.
    - Platelets ≥50 x 10 to the 9th/L independent of platelet transfusion support. For the screening platelets to be considered independent of platelet transfusion support, platelet count must be stable for 3-4 days after the transfusion.
    9. Biochemical laboratory test values must be within the following limits:
    - Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5 times
    the upper limit of normal (x ULN)
    - Creatinine clearance >40 mL/min
    - Total bilirubin ≤3.0 x ULN, except for subjects with Gilbert syndrome
    10. Women of childbearing potential and men who are sexually active must be practicing highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) during and after the study. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies. Men must agree to not father a child or donate sperm during and after the study. Women must agree not to donate eggs (ova, oocytes) for the purpose of assisted reproduction. For females and males, these restrictions apply for at least 3 months after the last dose of study drug.
    11. A woman of childbearing potential must have a negative highly sensitive serum
    (B-human chorionic gonadotropin [B-hCG]) or urine pregnancy test at Screening.
    12. Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
    1. 18 años de edad
    2. SMD con arreglo a los criterios de la Organización Mundial de la Salud confirmado por aspirado y biopsia de médula ósea en las 12 semanas previas a la primera dosis. El promotor deberá aprobar el informe del laboratorio local de este aspirado y biopsia de médula ósea.
    3. Riesgo bajo o intermedio-1 según el IPSS
    4. Dependiente de transfusiones de glóbulos rojos.
    • Haber recibido al menos 4 unidades de eritrocitos a lo largo de cualesquiera 8 semanas consecutivas durante las 16 semanas anteriores a la aleatorización.
    • Valor de Hb pretransfusión ≤ 9,0 g/dl.
    La documentación original de las transfusiones deberá ser verificada por el promotor.
    5. Recaída o refractario al tratamiento con AEE; el promotor deberá verificar este diagnóstico, lo que se define por el cumplimiento de cualquiera de los criterios siguientes:
    • Haber recibido tratamiento al menos durante 8 semanas con una dosis semanal mínima de epoetina alfa 40.000 U, epoetina beta 30.000 U o darbepoetina alfa 150 µg (o agente/dosis equivalente), sin haber logrado un incremento de la Hb ≥ 1,5 g/dl o una disminución de la necesidad de transfusiones de eritrocitos de al menos 4 unidades durante 8 semanas;
    • Dependencia de las transfusiones o reducción de la Hb ≥ 1,5 g/dl después de la mejoría hematológica, en ausencia de otra explicación;
    • EPO endógena sérica > 500 mU/ml.
    La documentación original del fracaso del tratamiento con AEE deberá ser verificada por el promotor.
    6. Reservas de hierro apropiadas, definidas como una saturación de transferrina superior al 20 % y ferritina sérica mayor de 400 ng/ml, medidas dentro del periodo de selección, o reservas de hierro apropiadas demostradas por un examen reciente de la médula ósea (en las 12 semanas anteriores a la primera dosis) con tinción de hierro.
    7. Estado funcional del ECOG 0, 1 o 2
    8. Los valores de las pruebas analíticas hematológicas deben estar comprendidos dentro de los límites siguientes:
    • RAN ≥ 1,0 x 109/l (es decir, ≥1.000/mm3) independiente del apoyo con factores de crecimiento. Para que el RAN de la selección se considere independiente de los factores de crecimiento, deberá respetarse un período de 7 días tras la suspensión de estos, o de 7 semividas del factor de crecimiento usado, lo que suponga más tiempo.
    • Recuento de plaquetas ≥ 50 x 109/l independiente del apoyo con transfusiones de plaquetas. Para que el recuento de plaquetas de la selección se considere independiente del apoyo con transfusión de plaquetas, el recuento de plaquetas deberá mantenerse estable durante 3-4 días después de la transfusión.
    9. Los valores de la pruebas analíticas de bioquímica deben estar comprendidos dentro de los límites siguientes:
    • Aspartato aminotransferasa (AST) y alanina aminotransferasa (ALT) ≤ 2,5 veces el límite superior de la normalidad (x LSN)
    • Aclaramiento de creatinina > 40 ml/min
    • Bilirrubina total ≤ 3.0 x LSN, excepto en sujetos con síndrome de Gilbert.
    10. Las mujeres en edad fértil y los varones sexualmente activos deben usar un método anticonceptivo muy eficaz (con una tasa de fracaso <1 % al año cuando se usa de forma constante y correcta) durante y después del estudio. El uso de anticonceptivos por los varones y las mujeres se ajustará a la normativa local en materia de uso de métodos anticonceptivos para sujetos que participan en estudios clínicos. Los varones deberán comprometerse a no engendrar hijos ni donar semen durante y después del estudio. Las mujeres deberán comprometerse a no donar óvulos (ovocitos) con fines de reproducción asistida. En las mujeres y los varones, estas restricciones se mantendrán durante al menos los 3 meses siguientes a la última dosis de fármaco del estudio.
    11. Las mujeres en edad fértil deberán tener un resultado negativo en una prueba muy sensible de embarazo en suero (gonadotropina coriónica humana β [β hCG]) u orina en el momento de la selección.
    12. Cada sujeto (o su representante legal) deberán firmar un documento de consentimiento informado (DCI) que indique que entiende el objetivo del estudio y los procedimientos que exige y que está dispuesto a participar en él. Los pacientes deberán ser capaces de cumplir las prohibiciones y limitaciones especificadas en este protocolo y estar dispuestos a cumplirlas.
    E.4Principal exclusion criteria
    1. Known allergies, hypersensitivity, or intolerance to talacotuzumab and daratumumab or their excipients
    2. Received any chemotherapy, immunomodulatory or immunosuppressive therapy, corticosteroids (>30 mg/day prednisone or equivalent) within 28 days prior to randomization
    3. Received other treatments for MDS within 28 days prior to first dose (eg, azacitidine, decitabine, lenalidomide, ESA (8 weeks for long-acting ESAs)
    4. History of hematopoietic stem cell transplant
    5. Del (5q) karyotype unless treatment with lenalidomide has failed. Failure is defined as either:
    1) having received at least 3 months of lenalidomide treatment without RBC
    transfusion benefit (IWG 2006);
    2) progression or relapse after hematologic improvement with lenalidomide (IWG 2006);
    3) discontinuation of lenalidomide due to toxicity; or
    4) unable to receive lenalidomide due to a contraindication. Source documentation for lenalidomide treatment failure must be verified by the sponsor.
    6. Anemia attributed to factors other than MDS (including hemolysis, chronic renal failure, hepatitis, gastrointestinal bleeding)
    7. Major surgery within 4 weeks prior to first dose (excludes the placement of a vascular access device and other minor surgical procedures)
    8. Active malignancy other than MDS ≤3 years before first dose, except:
    - Adequately treated non-melanoma skin cancer or lentigo maligna without current evidence of disease
    - Adequately treated cervical carcinoma in situ without current evidence of disease
    9. Clinically significant cardiovascular disease including:
    - myocardial infarction within 6 months of screening
    - unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, cardiac disease meeting New York Heart Association
    Class 3-4 definition)
    - uncontrolled or symptomatic cardiac arrhythmias
    - screening 12-lead ECG showing a baseline corrected QT interval (QTc) >470 msec
    10. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal
    11. Known moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification. Note that subjects who currently have
    controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
    12. Uncontrolled active systemic infection requiring IV antibiotics
    13. Known history of human immunodeficiency virus (HIV) infection
    14. Active systemic hepatitis infection requiring treatment or other clinically active liver disease
    15. Females who are pregnant or are breastfeeding
    16. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety, or put the study outcomes at undue risk. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
    1. Alergia, hipersensibilidad o intolerancia conocidas a talacotuzumab o daratumumab y sus excipientes
    2. Haber recibido cualquier quimioterapia, tratamiento inmunomodulador o inmunosupresor o corticosteroides (> 30 mg/día de prednisona o equivalente) en los 28 días previos a la aleatorización.
    3. Haber recibido otros tratamientos para el SMD en los 28 días previos a la primera dosis (p. ej., azacitidina, decitabina, lenalidomida o AEE [8 semanas en el caso de los AEE de acción prolongada]).
    4. Antecedentes de trasplante de células progenitoras hematopoyéticas.
    5. Cariotipo del(5q), salvo si el tratamiento con lenalidomida ha fracasado. El fracaso se define como alguna de las circunstancias siguientes: 1) haber recibido tratamiento con lenalidomida durante al menos 3 meses sin beneficio en cuanto a las transfusiones de eritrocitos (IWG 2006); 2) progresión o recaída después de una mejoría hematológica con lenalidomida (IWG 2006); 3) suspensión del tratamiento con lenalidomida debido a toxicidad, o 4) imposibilidad de recibir lenalidomida debido a una contraindicación. La documentación original del fracaso del tratamiento con lenalidomida deberá ser verificada por el promotor.
    6. Anemia atribuida a factores distintos del SMD (tales como hemólisis, insuficiencia renal crónica, hepatitis o hemorragia gastrointestinal).
    7. Cirugía mayor en las 4 semanas previas a la primera dosis (se excluyen la implantación de un dispositivo de acceso vascular y otros procedimientos quirúrgicos menores).
    8. Neoplasia maligna activa distinta del SMD ≤ 3 años antes de la primera dosis, excepto:
    • Cáncer de piel distinto del melanoma o lentigo maligno tratado adecuadamente sin indicios actuales de enfermedad.
    • Carcinoma in situ de cuello uterino tratado adecuadamente sin indicios actuales de enfermedad.
    9. Enfermedad cardiovascular de importancia clínica, tal como:
    • Infarto de miocardio en los 6 meses previos a la selección.
    • Enfermedad/trastorno inestable o no controlado relacionado con o que afecta a la función cardíaca (p. ej., angina inestable, enfermedad cardíaca que cumple la definición de clase 3-4 de la New York Heart Association).
    • Arritmias cardíacas sintomáticas o no controladas.
    • ECG de 12 derivaciones en la selección que muestra un intervalo QT corregido (QTc) basal > 470 ms.
    10. Enfermedad pulmonar obstructiva crónica (EPOC) con un volumen espiratorio forzado en 1 segundo (FEV1) < 50 % del valor normal previsto.
    11. Asma persistente moderado o grave durante los últimos 2 años o asma no controlado de cualquier clasificación. Nota: se permite la participación de sujetos que actualmente tengan asma intermitente controlado o asma leve controlado.
    12. Infección sistémica activa no controlada que precise antibióticos IV.
    13. Antecedentes conocidos de infección por el virus de la inmunodeficiencia humana (VIH).
    14. Infección sistémica activa por virus de hepatitis que precisa tratamiento u otra hepatopatía clínicamente activa.
    15. Mujer embarazada o en período de lactancia.
    16. Cualquier enfermedad, proceso médico o disfunción orgánica potencialmente mortal que, en opinión del investigador, podría comprometer la seguridad del sujeto o suponer un riesgo inaceptable para los resultados del estudio. Cualquier trastorno por el que, en opinión del investigador, la participación en el estudio no sea lo mejor para el sujeto (por ejemplo, afectaría a su bienestar) o pueda impedir, limitar o constituir un factor de confusión en las evaluaciones especificadas en el protocolo.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is 8-week RBC TI, defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.
    El objetivo principal es la IT de células sanguíneas rojas durante 8 semanas, definida como ausencia de transfusión de células sanguíneas rojas durante cualquier período de 56 días consecutivos (8 semanas) después de la aleatorización.
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months after the last subject is randomized
    6 meses después de que se haya incluido el último paciente
    E.5.2Secondary end point(s)
    1.) Transfusion independence lasting 168 days (24 weeks)
    2.) Time to TI
    3.) Duration of TI
    4.) Transfusions and myeloid growth factors usage
    5.) HI (including HI-E, HI-P, HI-N), CR, PR and cytogenetic response per IWG 2006
    6.) Overall survival
    7.) Progression to AML
    1. Independencia de transfusiones que dure 168 días (24 semanas)
    2. Tiempo a la IT
    3. Duración de la IT
    4. Uso de transfusiones y factores de crecimiento mieloides.
    5. Mejora hematológica (incluyendo MH-E, MH-P, MH-N), RC, RP y respuesta citogenética según IWG2006
    6. Supervivencia global
    7. Progresión a LMA
    E.5.2.1Timepoint(s) of evaluation of this end point
    1.) 6 months after the last subject is randomized
    2.) 6 months after the last subject is randomized
    3.) 6 months after the last subject is randomized
    4.) 6 months after the last subject is randomized
    5.) 6 months after the last subject is randomized
    6.) 12 months after the last subject is randomized
    7.) 12 months after the last subject is randomized
    1. 6 meses después de que se haya incluido el último paciente
    2. 6 meses después de que se haya incluido el último paciente
    3. 6 meses después de que se haya incluido el último paciente
    4. 6 meses después de que se haya incluido el último paciente
    5. 6 meses después de que se haya incluido el último paciente
    6. 12 meses después de que se haya incluido el último paciente
    7. 12 meses después de que se haya incluido el último paciente
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic 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 No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group 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) No
    E.8.2.2Placebo No
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA24
    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
    Belgium
    France
    Italy
    Netherlands
    Russian Federation
    Spain
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study is defined as 1 year after the last subject is randomized or anytime the sponsor terminates the study.
    El final del estudio esta definido 1 año despues del ultimo paciente randomizado o en el momento en el que el sponsor decida terminar el estudio.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months7
    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: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 60
    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 who are continuing to derive benefit from treatment as assessed by their investigator will continue to receive treatment and be monitored for safety by the sponsor.
    Los pacientes que continuen recibiendo beneficio del tratamiento a criterio del investigador continuaran recibiendo tratamiento y seran monitorizados por seguridad por parte del sponsor.
    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 Decision2017-02-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-01-20
    P. End of Trial
    P.End of Trial StatusTemporarily Halted
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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