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    Summary
    EudraCT Number:2021-000705-25
    Sponsor's Protocol Code Number:AT148002
    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:2021-06-23
    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 number2021-000705-25
    A.3Full title of the trial
    A PHASE 1/2 STUDY OF ALX148 IN COMBINATION WITH AZACITIDINE IN PATIENTS WITH HIGHER RISK MYELODYSPLASTIC SYNDROME (MDS) (ASPEN-02)
    ESTUDIO DE FASE I/II DE ALX148 EN COMBINACIÓN CON AZACITIDINA EN PACIENTES CON SÍNDROME MIELODISPLÁSICO (SMD) DE MAYOR RIESGO (ASPEN-02)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial in patients with with higher risk myelodysplastic syndrome looking at combining ALX148 and Azacitidine
    Ensayo en pacientes con síndrome mielodisplásico de mayor riesgo que analiza la combinación de ALX148 y Azacitidina
    A.3.2Name or abbreviated title of the trial where available
    ASPEN-02
    A.4.1Sponsor's protocol code numberAT148002
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04417517
    A.5.4Other Identifiers
    Name:US IND NumberNumber:147991
    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 SponsorALX Oncology Inc.
    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 supportALX Oncology Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationALX Oncology Inc.
    B.5.2Functional name of contact pointVP, Clinical Development
    B.5.3 Address:
    B.5.3.1Street Address866 Malcolm Rd., Suite 100
    B.5.3.2Town/ cityBurlingame, CA
    B.5.3.3Post code94010
    B.5.3.4CountryUnited States
    B.5.4Telephone number1 650 226 8293
    B.5.5Fax number1 650 466-7138
    B.5.6E-mailkatherine@alxoncology.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 nameALX148
    D.3.2Product code ALX148
    D.3.4Pharmaceutical form Solution for injection
    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 INNNA
    D.3.9.1CAS number 2484949-51-9
    D.3.9.2Current sponsor codeALX148
    D.3.9.3Other descriptive nameALX148
    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 No
    D.IMP: 2
    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 Azacitidine
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare S.L.U.
    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 nameAzacitidine
    D.3.4Pharmaceutical form Powder for suspension for injection
    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 INNAZACITIDINE
    D.3.9.1CAS number 320-67-2
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB05624MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    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
    Patients with higher risk myelodysplastic syndrome (MDS) who have not yet been treated for their disease
    Pacientes con síndromes mielodisplásicos (SMD) de alto riesgo que no han sido tratado para su enfermedad
    E.1.1.1Medical condition in easily understood language
    Myelodysplastic syndrome is a type of cancer where the blood-forming cells in the bone marrow are abnormal
    Los síndromes mielodisplásicos son un tipo de cáncer en los que las células que producen la sangre en la médula ósea no son normales
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10028533
    E.1.2Term Myelodysplastic syndrome
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the effect of ALX148 administered at the RP2D determined in Phase 1 in combination with AZA versus AZA alone on the investigator-assessed complete response rate (CRR) per IWG 2006 criteria in adult patients with previously-untreated higher risk MDS (IPSS-R score >3.5)
    Evaluar el efecto de ALX148 administrado a la DRF2 determinada en la fase I en combinación con AZA frente a AZA en monoterapia en la tasa de respuesta completa (TRC) evaluada por el investigador según los criterios del IWG de 2006 en pacientes adultos con SMD de mayor riesgo
    sin tratamiento previo (puntuación IPSS-R >3,5)
    E.2.2Secondary objectives of the trial
    - To assess the effect of ALX148 administered at the RP2D determined in Phase 1 in combination with
    AZA versus AZA alone on the complete response rate (CRR) per IWG 2006 criteria as determined by
    independent central review in adult patients with previously-untreated higher risk MDS (IPSS-R score
    >3.5)
    - To assess secondary measures of efficacy for ALX148 administered in combination with AZA versus
    AZA alone
    - To assess the safety and tolerability of ALX148 administered in combination with AZA versus AZA
    alone
    - To assess if ALX148 in combination with AZA improves global health status/quality of life
    (GHS/QoL) versus AZA alone based on patient reported outcome (PRO) assessment
    - Evaluar el efecto de ALX148 administrado a la DRF2 determinada en la fase I en combinación con AZA frente a AZA en monoterapia en la tasa de respuesta completa (TRC) según los criterios del IWG de 2006, en base a lo determinado mediante revisión central independiente, en pacientes adultos con SMD de mayor riesgo sin tratamiento previo (puntuación IPSS-R >3,5)
    - Evaluar las medidas secundarias de la eficacia de ALX148 administrado en combinación con AZA frente a AZA en monoterapia
    - Evaluar la seguridad y tolerabilidad de ALX148 administrado en combinación con AZA frente a AZA en monoterapia
    - Evaluar si ALX148 en combinación con AZA mejora el estado de salud general/la calidad de vida (ESG/CdV) frente a AZA en monoterapia en base a la evaluación de los resultados
    notificados por el paciente (RNP)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Adult patients with documented diagnosis of higher risk MDS (IPSS-R score >3.5) who have had no prior exposure to hypomethylating agents or cytotoxic chemotherapy (prior use of single agent lenalidomide for low or intermediate-1 risk MDS with deletion 5q abnormality is allowed) for the treatment of MDS, and are considered appropriate candidates for single-agent AZA.
    2. Bone marrow with >5% to <20% myeloblasts.
    3. Adequate Renal Function with estimated creatinine clearance > or =30 mL/min as calculated using the method standard for the institution.
    4. Adequate Liver Function, including:
    a. Total serum bilirubin < or =1.5 x ULN (< or =3.0 x ULN if the patient has documented Gilbert syndrome);
    b. Aspartate and alanine transaminase (AST and ALT) < or =3.0 x ULN; < or =5.0 x ULN if due to leukemic organ involvement;
    c. Alkaline phosphatase < or =2.5 x ULN; (< or =5.0 x ULN if bone or liver metastasis).
    5. WBC < 20,000/microL. Administration of hydroxyurea for WBC control is permitted during the screening period up to and including treatment day -1 of the study (ie, one day prior to starting study treatment).
    6. QTcF interval of < or =480 msec (Based upon mean value from triplicate ECGs).
    7. Age > or = 18 years because MDS is extremely rare in the pediatric (<18 yrs) population.
    8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0, 1 or 2.
    9. For Phase 1 only: resolved acute effects of any prior therapy to baseline severity or Grade < or =1 NCI CTCAE v.5.0 except for AEs not constituting a safety risk by Investigator judgment.
    10. Serum pregnancy test (for females of childbearing potential) negative at screening.
    11. Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 120 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the Investigator, he/she is biologically capable of having children and is sexually active.
    12. Evidence of a personally signed and dated informed consent document indicating that the patient (or legal representative) has been informed of all pertinent aspects of the study before any study-specific activity is performed.
    13. Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory, tests and other procedures.
    1. Pacientes adultos con diagnóstico documentado de SMD de alto riesgo (puntuación IPSS-R >3,5) que no hayan tenido una exposición previa a agentes hipometilantes o quimioterapia citotóxica (se permite el uso previo de lenalidomida como agente único para SMD de riesgo bajo o intermedio-1 con anormalidad de deleción 5q) para el tratamiento de SMD, y que se consideren candidatos apropiados para AZA como agente único.
    2. Médula ósea con >5% a <20% de mieloblastos.
    3. Función renal adecuada con un aclaramiento de creatinina estimado > o =30 ml/min según lo calculado mediante el método estándar de la institución.
    4. Función hepática adecuada, lo que incluye:
    a. Bilirrubina sérica total < o =1,5 x LSN (< o =3,0 x LSN si el paciente presenta síndrome de Gilbert documentado);
    b. Aspartato y alanina transaminasa (AST y ALT) < o =3,0 x LSN; < o =5,0 x LSN si se debe a afectación orgánica por leucemia;
    c. Fosfatasa alcalina < o =2,5 x LSN (< o =5,0 x LSN en presencia de metástasis ósea o hepática).
    5. Leucocitos < 20 000/microl. Se permite la administración de hidroxiurea para el control de los leucocitos durante la fase de selección y hasta el día -1 de tratamiento del estudio, inclusive (es decir, un día antes de iniciar el tratamiento del estudio).
    6. Intervalo QTcF de ≤480 ms (en base al valor medio obtenido de los ECG por triplicado).
    7. Edad > o = 18 años porque el SMD es extremadamente raro en la población pediátrica (<18 años).
    8. El estado general (EG) debe ser de 0, 1 o 2 según la escala del Grupo de Oncología Cooperativo del Este (Eastern Cooperative Oncology Groupnull, ECOG).
    9. Solo para la fase I: efectos agudos derivados de cualquier tratamiento previo resueltos hasta alcanzar la intensidad inicial o grado ≤1 según los CTCAE v.5.0 del NCI, excepto para los AA que no constituyan un riesgo para la seguridad a criterio del investigador.
    10. Prueba de embarazo en suero (para las mujeres en edad fértil) negativa en la selección.
    11. Los pacientes en edad fértil de ambos sexos deben aceptar utilizar un método anticonceptivo altamente eficaz durante todo el estudio y durante al menos 120 días después de la última dosis del tratamiento asignado. Un/a paciente está en edad fértil si, en opinión del investigador, es biológicamente capaz de tener hijos y es sexualmente activo/a.
    12. Constancia de un documento de consentimiento informado fechado y firmado personalmente que indique que se ha informado al paciente (o a un representante legal) de todos los aspectos pertinentes del estudio antes de que se realice cualquier actividad específica del estudio.
    13. Los pacientes deben estar dispuestos a cumplir con las visitas programadas, los planes de tratamiento, las pruebas analíticas y otros procedimientos del estudio, y poder hacerlo.
    E.4Principal exclusion criteria
    1. Patients with a history of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction secondary to an acquired allo-antibody.
    2. Previous allogeneic hematopoietic stem cell transplant (allo-HSCT) for MDS or AML. If allo-HSCT was performed for another disease, patient must be at least a year post-HSCT, off all treatment for graft-versus-host disease (GVHD), and without any active GVHD.
    3. Prior treatment with any anti-CD47 or anti-SIRPalpha agent.
    4. Prior treatment with any hypomethylating agents or cytotoxic chemotherapy for MDS (except hydroxyurea up to day -1 of study and lenalidomide for low or intermediate-1 risk MDS with deletion 5q abnormality).
    5. Patients with MPN/MDS overlap syndromes, including CMML.
    6. Prior treatment with myeloid growth factors and erythropoiesis stimulating agents (ESAs) must be discontinued a minimum of 4-5 half-lives prior to initiation of study treatment.
    7. Patients with intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or patients who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients).
    8. Any experimental antibodies or live vaccines in the last 28 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed.
    9. Known active viral infections, including hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) related illness, or known active infection with SARS-CoV-2 (testing to be performed per local criteria).
    10. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, NYHA Class II or greater congestive heart failure, uncontrolled hypertension, cerebrovascular accident, transient ischemic attack, deep venous thrombosis (except for thrombi considered device-associated and not clinically significant), arterial thrombosis, symptomatic pulmonary embolism, or any other significant thromboembolism. Any major surgery, within 28 days prior to enrollment.
    11. Current active treatment in another interventional therapeutic clinical study.
    12. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate/breast/other cancer under control with hormone therapy alone, or other cancer from which the subject has been disease free for at least 2 years and felt to be at low risk for recurrence by the treating physician.
    13. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
    14. Other severe acute or chronic medical or psychiatric condition, including uncontrolled systemic infection, recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
    15. Males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 120 days after last dose of investigational product.
    16. Patients who are pregnant or breastfeeding.
    1. Pacientes con antecedentes de anemia hemolítica autoinmunitaria, trombocitopenia autoinmunitaria o reacción transfusional hemolítica secundaria a un aloanticuerpo adquirido.
    2. Alotrasplante de células madre hematopoyéticas (alo-TCMH) previo para SMD o LMA. Si se realizó un alo-TCMH para otra enfermedad, el paciente debe haber estado sin recibir ningún tratamiento para la
    enfermedad de injerto contra huésped (EICH) y sin EICH activa durante al menos un año después del TCMH.
    3. Tratamiento previo con algún fármaco anti-CD47 o anti-SIRPalfa.
    4. tratamiento previo con agentes hipometilantes o quimioterapia citotóxica para el SMD (excepto hidroxiurea hasta el día -1 del estudio y lenalidomida para el SMD de riesgo bajo o intermedio-1 con anomalía de deleción de 5q).
    5. pacientes con síndromes de solapamiento de NMP/SMD, incluida la LMMC.
    6. El tratamiento previo con factores de crecimiento mieloide y agentes estimulantes de la eritropoyesis (AEE) debe interrumpirse un mínimo de 4-5 semividas antes del inicio del tratamiento del estudio.
    7. Pacientes con intolerancia o que han tenido una reacción alérgica o anafiláctica grave a anticuerpos o proteínas terapéuticas perfundidas o pacientes que han tenido una reacción alérgica o anafiláctica grave a
    alguna de las sustancias que se incluyen en el fármaco del estudio (incluidos los excipientes).
    8. Cualquier anticuerpo experimental o vacuna viva en los últimos 28 días antes de la primera dosis del fármaco del estudio. Ejemplos de vacuna de microorganismos vivos son, entre otras, las siguientes:
    sarampión, paperas, rubéola, varicela/zóster, fiebre amarilla, rabia, antituberculosa y tifus. Las vacunas inyectables contra la gripe estacional, por lo general, son vacunas elaboradas con virus muertos y están
    permitidas. Sin embargo, las vacunas antigripales intranasales (p. ej., FluMist) son vacunas vivas atenuadas y no están permitidas.
    9. Infecciones víricas activas conocidas, incluidas hepatitis B (VHB), hepatitis C (VHC), virus de la inmunodeficiencia humana (VIH), enfermedad relacionada con el síndrome de inmunodeficiencia adquirida (SIDA) o infección activa conocida por SARS-CoV-2 (las pruebas se realizarán según los criterios locales).
    10. Cualquiera de las siguientes afecciones en los 6 meses anteriores: infarto de miocardio, angina grave/inestable, injerto de derivación arterial coronario/periférico, insuficiencia cardíaca congestiva de clase II o superior según la NYHA, hipertensión no controlada, accidente cerebrovascular, accidente isquémico transitorio, trombosis venosa profunda (excepto los trombos que se consideren asociados al dispositivo y no clínicamente significativos), trombosis arterial, embolia pulmonar sintomática, o
    cualquier otra tromboembolia significativa. Cualquier cirugía mayor en los 28 días anteriores a la inscripción.
    11. Tratamiento activo actual en otro estudio clínico terapéutico intervencionista.
    12. Neoplasia maligna previa, excepto cáncer de piel basocelular o espinocelular tratado adecuadamente, cáncer cervicouterino in situ, cáncer de próstata/mama/otro cáncer bajo control solo con hormonoterapia u otro cáncer del que el paciente haya estado libre de enfermedad durante al menos 2 años y que el médico responsable del tratamiento considere de bajo riesgo de recurrencia.
    13. Presenta una enfermedad autoinmunitaria activa que ha necesitado tratamiento sistémico en los últimos 2 años (es decir, con fármacos modificadores de la enfermedad, corticoesteroides o fármacos inmunodepresores). El tratamiento de restitución (p. ej., tratamiento de restitución con tiroxina, insulina o corticoesteroides con dosis fisiológicas para la insuficiencia suprarrenal o pituitaria) no se considera una forma de tratamiento sistémico y está permitido.
    14. Otras patologías médicas o psiquiátricas graves agudas o crónicas, incluyendo infecciones sistémicas no controladas, comportamientos o pensamientos suicidas recientes (en el último año) o activos, o alteraciones en la analítica que puedan aumentar el riesgo asociado a la participación del estudio o a la administración del producto en investigación o que puedan interferir con la interpretación de los resultados del estudio y, a juicio del investigador, hagan que el paciente resulte inadecuado para su
    entrada en este estudio.
    15. Hombres y mujeres en edad fértil que no utilizan métodos anticonceptivos altamente eficaces o no aceptan el uso continuado de un método anticonceptivo altamente eficaz durante al menos 120 días después de la última dosis del producto en investigación.
    16. Pacientes embarazadas o en periodo de lactancia.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the Phase 2 part of the study is complete response rate (CRR), assessed by investigator using IWG 2006 response criteria for MDS, defined as a best response of CR, with the final analysis to be performed after the last patient has completed 6 cycles of treatment or is considered evaluable for response.
    El criterio de valoración primario de la parte de fase 2 del estudio es la tasa de respuesta completa (CRR), evaluada por el investigador utilizando los criterios de respuesta del IWG 2006 para SMD, definida como una mejor respuesta de CR, con el análisis final que se realizará después de que el último paciente haya completado 6 ciclos de tratamiento o se considere evaluable para la respuesta.
    E.5.1.1Timepoint(s) of evaluation of this end point
    In Phase 2, the final analysis to be performed after the last patient has completed 6 cycles of treatment or is considered evaluable for response.
    En la fase 2, el análisis final se realizará después de que el último paciente haya completado 6 ciclos de tratamiento o se considere evaluable para la respuesta.
    E.5.2Secondary end point(s)
    • Incidence of marrow CR, objective response rate (ORR), hematologic improvement (HI) in erythrocytes (E), platelets (P), and neutrophils (N), red blood cell (RBC) and platelet (PLT) transfusion independence, frequency and level of measurable residual disease (MRD)
    • Duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), time to progression (TTP).
    • Percentage of patients able to proceed to allogeneic hematopoietic stem cell transplant (allo-HSCT).
    • Changes in global health status/quality of life (GHS/QoL) status based on patient reported outcome (PRO) assessment (Phase 2 only).
    • Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v. 5.0), timing, seriousness, and relationship to study therapy;
    • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing;
    • Pharmacokinetic parameters of ALX148 such as Cmax, Tmax, AUC, CL, and t1/2 as data permit;
    • Immunogenicity; Human serum ADA (anti-ALX148 antibody) samples will be analyzed for the presence or absence of anti-ALX148 antibodies.
    - Incidencia de la RC medular, tasa de respuesta objetiva (ORR), mejora hematológica (HI) en eritrocitos (E), plaquetas (P) y neutrófilos (N), independencia de las transfusiones de glóbulos rojos (RBC) y plaquetas (PLT), frecuencia y nivel de enfermedad residual medible (MRD).
    - Duración de la respuesta (DOR), supervivencia libre de eventos (EFS), supervivencia libre de progresión (PFS), supervivencia global (OS), tiempo hasta la progresión (TTP).
    - Porcentaje de pacientes capaces de proceder a un trasplante alogénico de células madre hematopoyéticas (allo-HSCT).
    - Cambios en el estado de salud global/calidad de vida (GHS/QoL) basados en la evaluación de los resultados comunicados por los pacientes (PRO) (sólo en la fase 2).
    - Acontecimientos adversos caracterizados por el tipo, la frecuencia, la gravedad (según los Criterios Terminológicos Comunes para Acontecimientos Adversos del Instituto Nacional del Cáncer (NCI CTCAE v. 5.0), el momento, la gravedad y la relación con el tratamiento del estudio;
    - Anomalías de laboratorio caracterizadas por el tipo, la frecuencia, la gravedad (según la clasificación del NCI CTCAE v. 5.0) y el momento;
    - Parámetros farmacocinéticos de ALX148, como Cmáx, Tmáx, AUC, CL y t1/2, según lo permitan los datos;
    - Inmunogenicidad; Se analizarán muestras de suero humano ADA (anticuerpos anti-ALX148) para detectar la presencia o ausencia de anticuerpos anti-ALX148.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Duration of response (DOR) is measured from the time measurement criteria are first met for CR, PR, mCR, CyR, or HI, until the first date that progressive disease (PD) is documented. Duration of CR is also measured from the time measurement criteria are first met for CR only, until the first date that progressive disease (PD) is documented. Patients who do not have any documentation of progression will be censored at their last tumor assessment. DOR will be evaluated in the responders population.
    Time to progression (TTP) is measured from start of treatment until progressive disease (PD) is documented. Patients who do not have any documentation of progression will be censored at their last tumor assessment.
    La DDR se mide desde el momento en que se cumplen por primera vez los criterios de medición para la RC, la RP, la RCm, la CyR o la HI, hasta la primera fecha en que se documenta la enfermedad progresiva (EP). La duración de la RC también se mide desde el momento en que se cumplen por primera vez los criterios de medición para la RC únicamente, hasta la primera fecha en que se documenta la enfermedad progresiva (EP). Los pacientes que no tengan ninguna documentación de progresión serán censurados en su última evaluación del tumor. El DOR se evaluará en la población de respondedores. El tiem TTP se mide desde el inicio del tratamiento hasta progresión. Los pacientes que no tengan ninguna documentación de progresión serán censurados en su última evaluación del tumor.
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability; Immunogenicity; Pharmacodynamic for CD47 occupancy
    Tolerabilidad, immunogenicidad, farmacodinámica para CD45
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open 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) Yes
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    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
    Korea, Republic of
    United States
    Belgium
    France
    Germany
    Italy
    Spain
    United Kingdom
    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 years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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: 77
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 78
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Subjects with no physical capacity to consent for themselves having an officially assigned legal representative authorised to consent on behalf/for the patient.
    Pacientes incapacitados físicamente para consentir por si mismos y que tengan asignados oficialmente un representante legal autorizado para consentir por ellos
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 65
    F.4.2.2In the whole clinical trial 155
    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)
    Usual care
    Tratamiento estándard
    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 Decision2021-08-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-23
    P. End of Trial
    P.End of Trial StatusOngoing
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