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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43977   clinical trials with a EudraCT protocol, of which   7312   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2015-003454-41
    Sponsor's Protocol Code Number:ACE-536-MDS-001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-02-03
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2015-003454-41
    A.3Full title of the trial
    A Phase 3, Double-Blind, Randomized Study To Compare The Efficacy And Safety Of Luspatercept (ACE-536) Versus Placebo For The Treatment Of Anemia Due To IPSS-R Very Low, Low, Or Intermediate Risk Myelodysplastic Syndromes In Subjects With Ring Syderoblasts Who Require Red Blood Cell Transfusion
    Estudio de fase 3, doble ciego y aleatorizado para comparar la eficacia y la seguridad de luspatercept (ACE-536) frente a placebo en el tratamiento de anemia debida a síndromes mielodisplásicos con riesgo muy bajo, bajo o intermedio según el sistema IPSS-R en sujetos con sideroblastos en anillo que necesitan transfusiones de eritrocitos
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study To Compare The Benefit And Safety Of Luspatercept (ACE-536) Versus Placebo in subjects with lack of normal Red Blood Cells Requiring Transfusion due to myelodysplastic syndromes (MDS) with ring sideroblasts
    Estudio para comparar la eficacia y la seguridad de luspatercept (ACE-536) frente a placebo en sujetos con anemia (falta de globulos rojos en sangre) debida a síndromes mielodisplásicos con sideroblastos en anillo que necesitan transfusiones.
    A.3.2Name or abbreviated title of the trial where available
    MEDALIST
    A.4.1Sponsor's protocol code numberACE-536-MDS-001
    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 SponsorCelgene Corporation
    B.1.3.4CountryUnited States
    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 supportCelgene Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPPD
    B.5.2Functional name of contact pointPPD Project Manager
    B.5.3 Address:
    B.5.3.1Street AddressC/Titán, 15 6th floor
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28045
    B.5.3.4CountrySpain
    B.5.4Telephone number+34900 834223
    B.5.6E-mailRegistroEspanolDeEstudiosClinicos@druginfo.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1331
    D.3 Description of the IMP
    D.3.1Product nameLuspatercept
    D.3.2Product code ACE-536
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    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 INNLuspatercept
    D.3.9.1CAS number 1373715-00-4
    D.3.9.2Current sponsor codeACE-536
    D.3.9.3Other descriptive nameLuspatercept
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number37.5
    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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1331
    D.3 Description of the IMP
    D.3.1Product nameLuspatercept
    D.3.2Product code ACE-536
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    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 INNLuspatercept
    D.3.9.1CAS number 1373715-00-4
    D.3.9.2Current sponsor codeACE-536
    D.3.9.3Other descriptive nameLuspatercept
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number87.5
    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 injection
    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
    Subjects with ring sideroblasts who require regular Red Blood Cell (RBC) Transfusions due to anemia due to Myelodysplastic Syndromes (MDS)
    Sujetos con sideroblastos en anillo que necesitan transfusiones de eritrocitos debido a anemia debida a síndromes mielodisplásicos (SMD)
    E.1.1.1Medical condition in easily understood language
    Subjects who require regular Red Blood Cell (RBC) Transfusions due to red blood cell count being lower than normal lead by a blood disorder due to damage in the blood-forming cells in the bone marrow
    Sujetos que necesitan transfusiones regulares de globulos rojos al tener un nº de globulos rojos en sangre es mas bajo de lo normal al estar dañada la formación de celulas sanguineas en médula ósea.
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10002272
    E.1.2Term Anemia
    E.1.2System Organ Class 100000004851
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate RBC transfusion independence (RBC-TI) of luspatercept compared with placebo for the treatment of anemia due to IPSS-R very low, low, or intermediate risk MDS in subjects with ring sideroblasts (? 15%) who require RBC transfusions
    Evaluar la independencia de las transfusiones de eritrocitos (ITE) del luspatercept comparado con un placebo en el tratamiento de la anemia debida a SMD con riesgo muy bajo, bajo o intermedio según el IPSS-R en sujetos con sideroblastos en anillo (? 15%) que precisan transfusiones de eritrocitos
    E.2.2Secondary objectives of the trial
    1. To assess the safety and tolerability of luspatercept compared with placebo
    2. To evaluate the effect of luspatercept on reduction in RBC transfusions, increase in hemoglobin, duration of RBC-TI, improvement in health-related quality of life (HRQoL) (ie, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30]), increase in neutrophils, increase in platelets, decrease in serum ferritin, decrease in iron chelation therapy use, and time to RBC-TI
    compared with placebo
    3. To evaluate population pharmacokinetics and exposure-response relationships for luspatercept in MDS subjects
    1. Valorar la seguridad y la tolerabilidad del luspatercept comparado con un placebo
    2. Evaluar el efecto del luspatercept en la reducción de las transfusiones de eritrocitos, el aumento de la hemoglobina, la duración de la ITE, la mejoría de la calidad de vida relacionada con la salud (CVRS) (es decir, el Cuestionario de Calidad de Vida de la Organización Europea de Investigación y Tratamiento del Cáncer [QLQ-C30 de la EORTC]), el aumento de los neutrófilos, el aumento de las plaquetas, el descenso de la ferritina sérica, el descenso del uso de tratamiento quelante del hierro y el tiempo hasta la ITE en comparación con un placebo
    3. Evaluar la farmacocinética poblacional y las relaciones exposición-respuesta del luspatercept en sujetos con SMD
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject is maior or equal to 18 years of age the time of signing the informed consent form (ICF).
    2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
    3. Documented diagnosis of MDS according to WHO 2008 classification (Appendix B) that meets IPSS-R classification (Greenberg, 2012; Appendix D) of very low, low, or intermediate risk disease, and: Ring sideroblast maior or equal to 15% of erythroid precursors in bone marrow, and minor of 5% blasts in bone marrow
    4. Refractory or intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following:
    - Refractory to prior ESA treatment - documentation of non-response or response that is no longer maintained to prior ESA-containing regimen, either as single agent or combination (eg, with G-CSF); ESA regimen must have been either:
    a) recombinant human erythropoietin (rHu EPO) maior or equal 40,000 IU/wk for at least 8 doses or equivalent;
    OR
    b) darbepoetin alpha maior or equal to 500 ?g Q3W for at least 4 doses or equivalent;
    - Intolerant to prior ESA treatment - documentation of discontinuation of prior ESAcontaining regimen, either as single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an adverse event
    - ESA ineligible - Low chance of response to ESA based on endogenous serum erythropoietin level maior to 200 U/L for subjects not previously treated with ESAs
    5. If previously treated with ESAs, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), must have been discontinued more or iqual to 6 weeks prior to date of randomization.
    6. Requires RBC transfusions, as documented by the following criteria:
    - average transfusion requirement of maior or equal to 2 units/8 weeks of pRBCs confirmed for a minimum of 16 weeks immediately preceding randomization.
    - no consecutive 56-day period that was RBC transfusion-free during the 16 weeks immediately preceding randomization
    7. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
    8. Females of childbearing potential (FCBP) must:
    a) Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
    b) Either commit to true abstinence from heterosexual contact (which must be reviewed prior to each IP administration or on a monthly basis [eg, in the event of dose delays] and source documented) or agree to use, and be able to comply with, effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy.
    9. Male subjects must practice true abstinence* (which must be reviewed prior to each IP administration or on a monthly basis [eg, in the event of dose delays]) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks following investigational product discontinuation, even if he has undergone a successful vasectomy.
    10. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
    1. Edad mínima de 18 años en el momento de firmar el impreso de consentimiento informado (ICI).
    2. Comprender y firmar voluntariamente el ICI antes de que se realice cualquier valoración o procedimiento relacionado con el estudio.
    3. Diagnóstico documentado de SMD según la clasificación de 2008 de la OMS (apéndice B) que cumpla los criterios de la clasificación del IPSS-R ((Greenberg, 2012; apéndice D) de enfermedad con riesgo muy bajo, bajo o intermedio, y: Sideroblastos en anillo mayor o igual a 15% de los precursores eritroides en la médula ósea. Menor de
    5% de blastos en la médula ósea
    4. Resistencia o intolerancia al tratamiento previo con FEE o inelegibilidad para recibirlo, definidas como sigue:
    -Resistencia a tratamiento previo con FEE: documentación de falta de respuesta o de mantenimiento de la respuesta a un régimen previo que contenía FEE en monoterapia o en combinación (p. ej., con G-CSF); el régimen de FEE debe haber sido:
    - eritropoyetina humana recombinante (EPOHur), mayor o igual a 40.000 UI/semana durante al menos 8 dosis o su equivalente;
    O
    - darbepoetina alfa mayor o igual a 500 µg C3S durante al menos 4 dosis o su equivalente;
    ? Intolerancia a tratamiento previo con FEE: documentación de la interrupción de un régimen previo que contenía FEE, en monoterapia o en combinación (p. ej., con G CSF), en cualquier momento tras la introducción debido a intolerancia o a un acontecimiento adverso
    ? Inelegibilidad para FEE: probabilidad baja de respuesta a los FEE basándose en un nivel sérico de eritropoyetina endógena mayor a 200 U/l en sujetos no tratados previamente con FEE
    5. En caso de tratamiento previo con FEE, factor estimulante de colonias de granulocitos (G-CSF), factor estimulante de colonias de granulocitos y macrófagos (GM-CSF), deberá haberse interrumpido más o igual a 6 semanas antes de la fecha de aleatorización.
    6. Necesidad de transfusiones de eritrocitos, documentada por los criterios siguientes:
    ? necesidad media de transfusiones de mayor o igual a 2 unidades/8 semanas de concentrados de eritrocitos confirmada durante un mínimo de 16 semanas inmediatamente anteriores a la aleatorización.
    ? ningún período de 56 días consecutivos sin transfusión de eritrocitos durante las 16 semanas inmediatamente anteriores a la aleatorización
    7. Puntuación del estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0, 1 ó 2 (apéndice G).
    8. Las mujeres en edad fértil (MEF) deberán:
    a) Tener dos pruebas de embarazo negativas comprobadas por el investigador antes del inicio del tratamiento del estudio. Deberán aceptar someterse a pruebas de embarazo continuas durante el curso del estudio y después del final del tratamiento del estudio. Se hará así aunque las mujeres practiquen abstinencia completa* de las relaciones heterosexuales.
    b) Comprometerse a la abstinencia completa* de relaciones heterosexuales (que deberá revisarse antes de cada administración de PI o mensualmente [p. ej., si hay aplazamientos de dosis] y consignarse documentalmente) o aceptar (y ser capaz de cumplir) el uso de un método anticonceptivo eficaz sin interrupción 5 semanas antes del inicio del producto en investigación, durante el tratamiento del estudio (incluidas las suspensiones de dosis) y en las 12 semanas tras la interrupción del tratamiento del estudio.
    9. Los varones deberán: Practicar la abstinencia completa* (que deberá revisarse antes de cada administración de PI o mensualmente [p. ej., si hay aplazamientos de dosis] o aceptar usar preservativos durante las relaciones sexuales con una mujer embarazada o en edad fértil mientras participen en el estudio, durante las suspensiones de la dosis y durante al menos 12 semanas tras la interrupción del producto en investigación, aunque se haya sometido a vasectomía con éxito.
    10. Estar dispuestos a seguir el programa de visitas del estudio y los demás requisitos del protocolo y ser capaces de hacerlo.
    E.4Principal exclusion criteria
    1. Prior therapy with disease modifying agents or experimental agents for underlying MDS disease
    2. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
    3. MDS associated with del 5q cytogenetic abnormality
    4. Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
    5. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
    6. Prior allogeneic or autologous stem cell transplant
    7. Known history of diagnosis of AML
    8. Use of any of the following within 5 weeks prior to randomization:
    - Anticancer cytotoxic chemotherapeutic agent or treatment
    - Corticosteroid, except for subjects on a stable or decreasing dose for maior or equal to 1 week prior to randomization for medical conditions other than MDS
    - Iron-chelating agents, except for subjects on a stable or decreasing dose for at least 8 weeks prior to randomization
    - Other RBC hematopoietic growth factors (eg, Interleukin-3)
    9. Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) maior or equal to 100 mmHg despite adequate treatment.
    10. Absolute neutrophil count (ANC) minor to 500/?L (0.5 x 109/L)
    11. Platelet count minor to 50,000/?L (50 x 109/L)
    12. Estimated glomerular filtration rate (eGRF) or creatinine clearance minor to 40 mL/min
    13. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) maior or equal to 3.0 x upper limit of normal (ULN)
    14. Total bilirubin maior or equal to 2.0 x ULN.
    - Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (ie, ineffective erythropoiesis).
    - Subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of maior to 2% with either a positive Coombs? test or over 50% indirect bilirubin
    15. Prior history of malignancies, other than MDS, unless the subject has been free of the disease for more or equal to 5 years. However, subjects with the following history/concurrent conditions are allowed:
    - Basal or squamous cell carcinoma of the skin
    - Carcinoma in situ of the cervix
    -Carcinoma in situ of the breast
    - Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
    16. Major surgery within 8 weeks prior to randomization. Subjects must have completely recovered from any previous surgery prior to randomization
    17. History of stroke, deep venous thrombosis (DVT), pulmonary or arterial embolism within 6 months prior to randomization
    18. Pregnant or breastfeeding females
    19. Myocardial infarction, uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator within 6 months prior to randomization
    20. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment), known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) infection, and/or Hepatitis C (HCV) infection
    21. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product.
    22. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
    23. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
    24. Subject has any condition or concomitant medication that confounds the ability to interpret data from the study.
    1. Tratamiento previo con fármacos modificadores de la enfermedad o fármacos experimentales para el SMD subyacente
    2. Tratamiento previo con luspatercept (ACE-536) o sotatercept (ACE-011)
    3. SMD asociado con la anomalía citogenética del 5q
    4. SMD secundario, es decir, SMD que se sabe que ha surgido a consecuencia de una lesión química o de tratamiento con quimioterapia o radioterapia por otras enfermedades
    5. Anemia de importancia clínica conocida debida a déficit de hierro, vitamina B12 o folato, anemia hemolítica autoinmunitaria o hereditaria o hemorragia digestiva
    6. Alo o autotrasplante de células madre previo
    7. Antecedente conocido de diagnóstico de LMA
    8. Uso de cualquiera de los siguientes en las 5 semanas previas a la aleatorización:
    ? fármaco quimioterapéutico o tratamiento citotóxico contra el cáncer
    ? corticosteroides, excepto en los sujetos tratados con una dosis estable o descendente durante mayor o igual a 1 semana antes de la aleatorización por procesos médicos distintos del SMD
    ? quelantes del hierro, excepto en los sujetos tratados con una dosis estable o descendente durante al menos 8 semanas antes de la aleatorización
    ? otros factores de crecimiento hematopoyéticos de eritrocitos (p. ej., interleucina 3)
    9. Hipertensión incontrolada, definida como elevaciones repetidas de la presión arterial diastólica (PAD) mayor o igual a 100 mm Hg a pesar de tratamiento adecuado.
    10. Recuento absoluto de neutrófilos (RAN) menor a 500/?l (0,5 x 109/l)
    11. Recuento de plaquetas menor a 50.000/µl (50 x 109/l)
    12. Filtración glomerular estimada (FGe) o aclaramiento de creatinina menor a 40 ml/min
    13. Aspartato aminotransferasa/transaminasa glutamicooxaloacética sérica (AST/SGOT) o alanina aminotransferasa/transaminasa glutamicopirúvica sérica (ALT/SGPT) maior or equal to 3,0 x límite superior normal (LSN)
    14. Bilirrubina maior or equal to 2,0 x LSN.
    ? son aceptables concentraciones más altas si pueden atribuirse a destrucción activa de precursores de eritrocitos dentro de la médula ósea (es decir, eritropoyesis ineficaz)
    ? se excluirá a los sujetos si hay indicios de anemia hemolítica autoinmunitaria manifestada como un recuento de reticulocitos corregido mayor a 2% con una prueba de Coombs positiva o una bilirrubina indirecta superior al 50%
    15. Antecedentes de procesos malignos distintos del SMD, a menos que el sujeto lleve más o igual a 5 años sin la enfermedad. Sin embargo, puede incluirse a los sujetos con los antecedentes y los procesos concomitantes siguientes:
    ? Carcinoma basocelular o espinocelular de la piel
    ? Carcinoma in situ del cuello uterino
    ? Carcinoma in situ de la mama
    ? Hallazgo histológico casual de cáncer de próstata (T1a o T1b según el sistema de estadificación clínica TNM [tumor, ganglios, metástasis])
    16. Operación quirúrgica importante en las 8 semanas previas a la aleatorización. Los sujetos deberán haberse recuperado totalmente de cualquier intervención previa a la aleatorización
    17. Antecedentes de ictus, trombosis venosa profunda (TVP) y embolia pulmonar o arterial en los 6 meses previos a la aleatorización
    18. Embarazo o lactancia materna
    19. Infarto de miocardio, angina no controlada, insuficiencia cardíaca no controlada o arritmia cardíaca no controlada determinadas por el investigador en los 6 meses previos a la aleatorización
    20. Infección micótica, bacteriana o vírica sistémica no controlada (definida como signos y síntomas persistentes relacionados con la infección sin mejoría a pesar del tratamiento apropiado con antibióticos o antivíricos o cualquier otro tratamiento), infección con el virus de la inmunodeficiencia humana (VIH), infección activa con el virus de la hepatitis B (VHB) o infección con el virus de la hepatitis C (VHC) conocidas.
    21. Antecedentes de reacciones alérgicas o anafilácticas intensas o hipersensibilidad conocida a proteínas recombinantes o excipientes del producto en investigación (véase el Manual del investigador).
    22. Cualquier proceso médico, anomalía analítica o enfermedad psiquiátrica importante que impida al sujeto participar en el estudio.
    23. Cualquier circunstancia, incluida la presencia de anomalías analíticas, que entrañe un riesgo inaceptable para el sujeto si participa en el estudio.
    24. Cualquier circunstancia o medicación concomitante que altere la capacidad de interpretar los datos del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Red Blood Cell Transfusion Independence (RBC-TI) maior or equal to 8 weeks - Proportion of subjects who are RBC transfusion free over any consecutive 56-day period
    Independencia de las transfusiones de eritrocitos (ITE) mayor o igual a 8 semanas -Proporción de sujetos sin transfusiones de eritrocitos durante cualquier período de 56 días consecutivos
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 1 through Week 24
    Semana 1 a semana 24
    E.5.2Secondary end point(s)
    Key secondary endpoint
    1. RBC-TI maior or equal to 12 weeks - Proportion of subjects who are RBC transfusion free over any consecutive 84-day period
    2. RBC-TI maior or equal to 8 weeks - Proportion of subjects who are RBC transfusion free over any consecutive 56-day period
    3. Reduction in RBC units transfused over 16 weeks - Mean change in total RBC units transfused over a fixed 16-week period
    4. Modified hematologic improvement - erythroid (mHI-E) per IWG - Proportion of subjects achieving modified HI-E over any consecutive 56-day period
    5. Mean hemoglobin increase maior or equal to 1.0 g/dL - Proportion of subjects achieving hemoglobin (Hgb) increase from baseline maior or equal to 1.0 g/dL over any consecutive 56-day period in absence of RBC transfusions
    6. Duration of RBC-TI - Maximum duration of RBC transfusion independence for subjects who achieve RBC TI maior or equal to 8 weeks
    7. Health-related quality of life (HRQoL) - Change in EORTC QLQC30 score
    8. Hematologic improvement - neutrophils (HI-N) / (HI-P) per IWG - Proportion of subjects achieving HI-N / HI-P over any consecutive 56-day period
    9. Mean decrease in serum ferritin - Change in serum ferritin
    10. Mean decrease in iron chelation therapy (ICT) use - Change in mean daily dose of ICT
    11. Time to RBC-TI - Time from first dose to first onset of transfusion independence maior or equal to 8 weeks
    12. Progression to AML - Number and percentage of subjects progressing to AML; time to AML progression
    13. Overall survival - Time from date of randomization to death due to any cause
    14. Safety - Type, frequency, severity of AEs and relationship of AEs to luspatercept/placebo
    15. A population PK model - A Population PK model that describes the PK exposure data of luspatercept and associated variability.
    16. Exposure-response relationship for the primary efficacy endpoint, AEs of interest, and selected secondary endpoints.
    17. Anti-drug antibodies (ADA) - Frequency of anti-drug antibodies and effects on efficacy, or safety, or PK
    Criterios de valoracion secundarios:
    1. ITE mayor o igual a 12 semanas -Proporción de sujetos sin transfusiones de eritrocitos durante cualquier período de 84 días consecutivos
    2. ITE mayor o igual a 8 semanas -Proporción de sujetos sin transfusiones de eritrocitos durante cualquier período de 56 días consecutivos
    3. Reducción de las unidades de eritrocitos transfundidas durante 16 semanas - cambio medio de las unidades totales de eritrocitos transfundidas durante un período fijo de 16 semanas
    4. Mejoría hematológica - eritroide modificada (MH-Em) según el IWG -Proporción de sujetos que consiguen MH-E modificada durante cualquier período de 56 días consecutivos
    5. Aumento medio de la hemoglobina mayor o igual a 1,0 g/dl -Proporción de sujetos que consiguen un aumento de la hemoglobina mayor o igual a 1,0 g/dl respecto a la basal durante cualquier período de 56 días consecutivos en ausencia de transfusiones de eritrocitos
    6. Duracion de la ITE -Duración máxima de la independencia de transfusiones de eritrocitos en los sujetos que consiguen ITE mayor o igual a 8 semanas
    7. Calidad de vida relacionada con la salud (CVRS) - Cambio de la puntuación del QLQ-C30 de la EORTC
    8. Mejoría hematológica - neutrófilos (MH-N)/ plaquetas (MH-P) según el IWG -Proporción de sujetos que consiguen MH-N/ MH-P modificada durante cualquier período de 56 días consecutivos
    9. Descenso medio de la ferritina sérica - cambio de la ferritina sérica
    10. Descenso medio del uso de tratamiento quelante del hierro (TQH) -cambio de la dosis media de TQH
    11. Tiempo hasta la ITE - Tiempo desde la primera dosis hasta el comienzo de independencia de las transfusiones mayor o igual a 8 semanas
    12. Progresión a LMA - Número y porcentaje de sujetos con progresión a LMA; tiempo hasta la progresión a LMA
    13. Supervivencia global - Tiempo desde la aleatorización hasta el fallecimiento por cualquier causa.
    14. Seguridad - Tipo, frecuencia e intensidad de los AA, y su relación con luspatercept o placebo
    15. Un modelo de FC poblacional - Un modelo de FC poblacional que describa los datos de exposición FC del luspatercept y la variabilidad asociada.
    16. Relación exposición-respuesta - Relación exposición-respuesta del criterio de valoración de la eficacia principal, los AA de interés y criterios de valoración secundarios seleccionados
    17. Anticuerpos antifármaco (AAF)- Frecuencia de anticuerpos antifármaco y efectos en la eficacia, la seguridad o la FC
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Week 1 to Week 24; Week 1 to Week 48
    2. Week 1 to Week 48
    3. Week 9 to 24; Week 32 to 48
    4 + 5. Week 1 to Week 24; Week 1 to Week 48
    6. Week 1 to Week 24; Week 1 to end of treatment
    7. Week 1 to Week 24; Baseline to end of treatment
    8. Week 1 to Week 24; Week 1 to Week 48
    9 + 10. Week 9 to 24; Week 32 to 48
    11. Week 1 to Week 24; Week 1 to Week 48
    12 + 13. Randomization to at least 2 years post last dose; Week 1 to Week 48
    14. Screening to 42 days post last dose; Week 1 to Week 48
    15 + 16. Randomization to end of treatment
    17. Randomization to end of treatment; if positive, every 12 weeks for up to 1 year or until return to baseline, whichever comes first
    1. Semana 1 a semana 24; Semana 1 a semana 48
    2. Semana 1 a semana 48
    3. Semana 9 a semana 24; Semana 32 a semana 48
    4 + 5. Semana 1 a semana 24; Semana 1 a semana 48
    6. Semana 1 a semana 24; Semana 1 al final de tto
    7. Semana 1 a semana 24;mto basal a final de tto
    8. Semana 1 a semana 24; Semana 1 a semana 48
    9 + 10. Semana 9 a semana 24; Semana 32 a semana 48
    11. Semana 1 a semana 24; Semana 1 a semana 48
    12 + 13. Desde aleatorización hasta al menos 2 años tras ultima dosis. Semana 1 a semana 48 .
    14. Desde selección a 42 días tras la última dosis; Semana 1 a semana 48
    15 + 16. Desde aleatorización a fin de tto
    17. Desde la aleatorización hasta el final del tratto; si son +, cada 12 semanas durante un máximo de 1 año o hasta la vuelta al estado basal, lo que antes ocurra.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarkers
    Biomarcadores
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over 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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA45
    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
    Canada
    France
    Germany
    Israel
    Italy
    Netherlands
    Spain
    Sweden
    United Kingdom
    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
    Either the date of the last visit of the last subject to complete the post-treatment follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol and/or SAP, whichever is the later date.
    El final del ensayo se define como la fecha de la última visita del último sujeto que complete el seguimiento postratamiento o la fecha de recepción de los últimos datos del último sujeto que se precisen para análisis principal, secundario o exploratorio según lo establecido en el protocolo o en el PAE, la que sea posterior.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    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: 62
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 148
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 140
    F.4.2.2In the whole clinical trial 210
    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 discontinue from treatment for any reason will be followed via telephone contact by the site for collection of data on survival, cause(s) of death, progression to AML, posttreatment therapy(ies) for MDS at the 42-Day and 12-Week Follow-up assessments and then every 3 months after the 12 Week Follow-up assessment for at least 2 years after last dose of IP or until death, lost to follow-up or withdrawal of consent from the study.
    El centro seguirá a los sujetos que interrumpan el tto por cualquier motivo mediante contacto tlf para recoger datos de supervivencia, causa o causas de muerte, progresión a LMA, terapias para SMD tras el tto en las valoraciones de seguimiento a los 42 días y las 12 semanas, y luego cada 3 meses tras la valoración de seguimiento a las 12 semanas dte al menos 2 años después de la última dosis de PI o hasta el fallecimiento, pérdida de seguimiento o la retirada del consentimiento para el estudio.
    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 Decision2016-05-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-11-26
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA