Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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


    The EU Clinical Trials Register currently displays   42517   clinical trials with a EudraCT protocol, of which   7000   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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:2020-005708-20
    Sponsor's Protocol Code Number:GS-US-548-5916
    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:2021-10-19
    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 number2020-005708-20
    A.3Full title of the trial
    A Phase 2 Study of Magrolimab Combination Therapy in Patients with Head and Neck Squamous Cell Carcinoma
    Estudio de fase 2 de tratamiento combinado con magrolimab en pacientes con carcinoma de células escamosas de cabeza y cuello
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study evaluating safety and efficacy of magrolimab in combination with chemotherapy for the treatment of Head and Neck Squamous Cell Carcinoma.
    Estudio para evaluar la seguridad y eficacia de magrolimab en combinación con quimioterapia para el tratamiento de carcinoma de células escamosas de cabeza y cuello
    A.4.1Sponsor's protocol code numberGS-US-548-5916
    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 SponsorGilead Sciences, 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 supportGilead Sciences, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGilead Sciences International Ltd.
    B.5.2Functional name of contact pointClinical Trials Mailbox
    B.5.3 Address:
    B.5.3.1Street AddressFlowers Building, Granta Park
    B.5.3.2Town/ cityAbington, Cambridge
    B.5.3.3Post codeCB21 6GT
    B.5.3.4CountryUnited Kingdom
    B.5.5Fax number+441223897284
    B.5.6E-mailclinical.trials@gilead.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 nameMagrolimab
    D.3.2Product code GS-4721
    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 INNMagrolimab
    D.3.9.2Current sponsor codeGS-4721
    D.3.9.3Other descriptive nameHu5F9-G4
    D.3.9.4EV Substance CodeSUB194348
    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 typeMonoclonal antibody
    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 Keytruda
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    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 namePembrolizumab
    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 INNPembrolizumab
    D.3.9.3Other descriptive namePembrolizumab
    D.3.9.4EV Substance CodeSUB167136
    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 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 typeHumanised Monoclonal Antibody
    D.IMP: 3
    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 Fluorouracil
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Ireland Ltd
    D.2.1.2Country which granted the Marketing AuthorisationIreland
    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 name5-Fluorouracil
    D.3.4Pharmaceutical form Solution for injection/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 INNFluorouracil
    D.3.9.3Other descriptive nameFLUOROURACIL
    D.3.9.4EV Substance CodeSUB07721MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.IMP: 4
    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 Cisplatin
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Ireland Ltd
    D.2.1.2Country which granted the Marketing AuthorisationIreland
    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 nameCisplatin
    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 INNCisplatin
    D.3.9.3Other descriptive nameCisplatin
    D.3.9.4EV Substance CodeSUB07483MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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.IMP: 5
    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 Carboplatin
    D.2.1.1.2Name of the Marketing Authorisation holderFresenius Kabi Deutschland GmbH
    D.2.1.2Country which granted the Marketing AuthorisationIreland
    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 nameCarboplatin
    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 INNCarboplatin
    D.3.9.3Other descriptive nameCARBOPLATIN
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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.IMP: 6
    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 Docetaxel Accord
    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 nameDocetaxel
    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 INNDocetaxel
    D.3.9.3Other descriptive nameDocetaxel
    D.3.9.4EV Substance CodeSUB12492MIG
    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 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
    Head and Neck Squamous Cell Carcinoma
    Carcinoma de células escamosas de cabeza y cuello
    E.1.1.1Medical condition in easily understood language
    Cancer in the Head and Neck
    Cancer en cabeza y cuello
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10060121
    E.1.2Term Squamous cell carcinoma of head and neck
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Safety Run-in Cohorts:
    To evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of magrolimab in combination with the following:
    - Pembrolizumab + 5-fluorouracil (5-FU) + platinum
    - Docetaxel
    Phase 2 Cohorts:
    - To evaluate the progression-free survival (PFS) with magrolimab in combination with pembrolizumab + 5-FU + platinum versus pembrolizumab + 5-FU + platinum by independent central review (Phase 2 Cohort 1)
    - To evaluate the efficacy of magrolimab in combination with pembrolizumab and magrolimab in combination with docetaxel as determined by the
    investigator-assessed objective response rate (ORR) (Phase 2 Cohorts 2 and 3)
    Cohortes de preinclusión de seguridad:
    •Evaluar la seguridad, la tolerabilidad y la dosis recomendada para la fase 2 (DRF2) de magrolimab en combinación con lo siguiente:
    Pembrolizumab + 5-fluorouracilo (5-FU) + platino
    Docetaxel
    Cohortes de fase 2:
    •Evaluar la supervivencia sin progresión (SSP) con magrolimab en combinación con pembrolizumab + 5-FU + platino en comparación con pembrolizumab + 5-FU + platino mediante revisión central independiente (cohorte 1 de fase 2)
    •Evaluar la eficacia de magrolimab en combinación con pembrolizumab y de magrolimab en combinación con docetaxel determinada por la tasa de respuesta objetiva (TRO) evaluada por el investigador (cohortes 2 y 3 de fase 2)
    E.2.2Secondary objectives of the trial
    Safety Run-in Cohorts:
    To evaluate the pharmacokinetics (PK) and immunogenicity of magrolimab in combination with anticancer therapies
    Phase 2 Cohorts:
    - To evaluate ORR by independent central review
    - To evaluate PFS by investigator assessment
    - To evaluate additional measures of efficacy, including duration of response (DOR) and overall survival (OS)
    - To evaluate the PK and immunogenicity of magrolimab in combination with anticancer therapies
    - To evaluate patient-reported outcomes (PROs)/quality-of-life measures
    Cohortes de preinclusión de seguridad:
    Evaluar la farmacocinética (FC) y la inmunogenicidad de magrolimab en combinación con tratamientos antineoplásicos
    Cohortes de fase 2:
    •Evaluar la TRO mediante revisión central independiente
    •Determinar la SSP de acuerdo con la evaluación del investigador
    •Evaluar variables adicionales de la eficacia, como la duración de la respuesta (DR) y la supervivencia global (SG)
    •Evaluar la FC y la inmunogenicidad de magrolimab en combinación con tratamientos antineoplásicos
    •Evaluar los resultados notificados por el paciente (RNP)/variables de calidad de vida
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    All Patients
    1) Patient has provided informed consent.
    2) Patient is willing and able to comply with clinic visits and
    procedures outlined in the study protocol.
    3) Male or female ≥ 18 years of age
    4) Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
    5) Laboratory measurements, blood counts:
    a) Hemoglobin ≥ 9.5 g/dL. Red blood cell transfusions are permitted to meet the hemoglobin inclusion criteria, within limits set per exclusion criterion 6.
    b) Absolute neutrophil count ≥ 1.5 x 10^9
    c) Platelets ≥ 100 x 10^9
    6) Laboratory measurements, renal function:
    a) Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or if elevated, a calculated glomerular filtration rate > 40 mL/min/1.73m^2
    7) Laboratory measurements, hepatic function:
    a) Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN or ≤ 5 x ULN in patients with liver metastases
    b) Total bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert’s syndrome or genetic equivalent
    8) Laboratory measurements, coagulation function:
    a) International normalized ratio or prothrombin time (PT) ≤ 1.5 x ULN unless patient is receiving anticoagulation therapy, as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use for anticoagulants
    b) Activated partial thromboplastin time or PTT ≤ 1.5 x ULN unless patient is receiving anticoagulation therapy, as long as PT or PTT is within therapeutic range of intended use for anticoagulants
    9) Pretreatment blood cross-match completed
    10) Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
    11) Measurable disease according to RECIST, version 1.1
    12) Patients must be willing to provide baseline tumor tissue from a core or excisional biopsy (fine needle aspirate is not adequate). A newly obtained biopsy (within 90 days prior to study treatment start) is strongly preferred, but an archival sample is acceptable. Patients will also be requested to consent to a mandatory on-treatment tumor biopsy, unless not feasible as determined by the investigator and discussed with the sponsor.

    Safety Run-in Cohort 1, Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab (if Applicable), and Phase 2 Cohorts 1 and 2:
    13) Patients with histologically or cytologically confirmed metastatic or locally recurrent HNSCC that is considered incurable by local therapies
    a) Patients should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy that was completed more than 6 months prior to signing consent if given as part of multimodal treatment for locally advanced disease is allowed.
    b) Eligible primary tumor locations include oropharynx, oral cavity, hypopharynx, and larynx.
    c) Patients may not have a primary tumor site of nasopharynx (any histology).

    Safety Run-in Cohort 1 and Phase 2 Cohort 1:
    In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Safety Run-in Cohort 1 and Phase 2 Cohort 1 must fulfill the following cohort-specific inclusion criterion:
    14) Patients with HNSCC per inclusion criterion 13 regardless of PD-L1 status

    Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab (if Applicable) and Phase 2 Cohort 2
    In addition to meeting the inclusion criteria for all patients, patients who are enrolled into the pre-expansion safety run-in cohort for
    magrolimab + pembrolizumab (if applicable) and Phase 2 Cohort 2
    must fulfill the following cohort specific inclusion criterion:
    15) Patients with HNSCC per inclusion criterion 13 with a PD-L1 CPS ≥ 1

    Safety Run-in Cohort 2 and Phase 2 Cohort 3:
    In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Safety Run-in Cohort 2 and Phase 2 Cohort 3 must fulfill the following cohort-specific inclusion criterion:
    16) Patients with histologically or cytologically confirmed locally advanced/mHNSCC regardless of PD-L1 status with at least 1 and no more than 2 lines of prior systemic anticancer therapy in the locally advanced/metastatic setting
    a) Eligible primary tumor locations include oropharynx, oral cavity, hypopharynx, and larynx.
    b) Patients may not have a primary tumor site of nasopharynx (any histology).
    Todos los pacientes
    1)Haber dado el consentimiento informado.
    2)Disposición y capacidad para cumplir con las visitas al centro y los procedimientos descritos en el protocolo del estudio.
    3)Hombre o mujer de edad ≥18 años.
    4)Estado funcional del Grupo Oncológico Cooperativo de la Costa Este (Eastern Cooperative Oncology Group, ECOG) ≤1.
    5)Valores analíticos, hemograma:
    a)Hemoglobina ≥9,5 g/dl. Se permiten las transfusiones de eritrocitos para satisfacer el criterio de inclusión relativo a la hemoglobina, dentro de los límites establecidos por el criterio de exclusión 6.
    b)Recuento absoluto de neutrófilos ≥1,5 x 10^9/ ml.
    c)Plaquetas ≥100 x 10^9 /ml.
    6)Valores analíticos, función renal:
    a)Creatinina sérica ≤1,5 x límite superior de la normalidad (LSN) o, si es elevada, índice de filtración glomerular calculado >40 ml/min/1,73 m2.
    7)Valores analíticos, función hepática:
    a)Aspartato-aminotransferasa y alanina-aminotransferasa ≤2,5 x LSN, o ≤5 x LSN en pacientes con metástasis hepáticas.
    b)Bilirrubina total ≤1,5 x LSN o ≤3,0 x LSN y principalmente no conjugada si el paciente tiene antecedentes documentados de síndrome de Gilbert o equivalente genético.
    8)Valores analíticos, coagulación:
    a)índice internacional normalizado o tiempo de protrombina (TP) ≤1,5 x LSN, a menos que el paciente esté recibiendo tratamiento anticoagulante, siempre que el TP o el tiempo de tromboplastina parcial (TTP) se encuentre dentro del intervalo terapéutico del uso previsto de los anticoagulantes.
    b)Tiempo de tromboplastina parcial activado o TTPa ≤1,5x LSN, a menos que el paciente esté recibiendo tratamiento anticoagulante, siempre que el TP o TTP se encuentre dentro del intervalo terapéutico del uso previsto de los anticoagulantes.
    9)Pruebas de compatibilidad cruzada antes del tratamiento completadas.
    10)Los hombres y mujeres en edad fértil que mantengan relaciones sexuales heterosexuales deben aceptar utilizar los métodos anticonceptivos especificados en el protocolo.
    11)Enfermedad medible conforme a los criterios RECIST, versión 1.1.
    12)Voluntad de proporcionar al inicio tejido tumoral de una biopsia por punción con aguja gruesa o de excisión (la biopsia aspirativa con aguja fina no es adecuada). Se prefiere una biopsia recién obtenida (en los 90 días previos al inicio del tratamiento del estudio), pero se acepta una muestra de archivo. También se pedirá a los pacientes que den su consentimiento para una biopsia tumoral obligatoria durante el tratamiento, a menos que el investigador determine que no es viable hacerla y lo ponga en conocimiento del promotor.
    Cohorte 1 de preinclusión de seguridad, cohorte 1 de preinclusión de seguridad previa a la expansión con magrolimab + pembrolizumab (si corresponde) y cohortes 1 y 2 de fase 2
    13)CECC localmente recidivante o metastásico confirmado mediante estudio de histología o citología que se considera incurable con tratamientos locales.
    a)No haber recibido tratamiento sistémico previo para enfermedad recidivante o metastásica. Se permite el tratamiento sistémico finalizado más de 6 meses antes de la firma del consentimiento, si se administró como parte de un tratamiento multimodal para la enfermedad localmente avanzada.
    b)Las localizaciones anatómicas aptas del tumor primario son la orofaringe, la cavidad bucal, la hipofaringe y la laringe.
    c)La localización anatómica del tumor primario no puede ser la nasofaringe (cualquier subtipo histológico).
    Cohorte 1 de preinclusión de seguridad y cohorte 1 de fase 2
    14)CECC de acuerdo con el criterio de inclusión 13, independientemente del estado de PD-L1.
    Cohorte de preinclusión de seguridad previa a la expansión con magrolimab + pembrolizumab (si corresponde) y cohorte 2 de fase 2
    15)CECC de acuerdo con el criterio de inclusión 13, con una CPS de PD-L1 ≥1.

    Cohorte 2 de preinclusión de seguridad y cohorte 3 de fase 2
    16)CECCm/localmente avanzado confirmado mediante estudio de histología o citología, independientemente del estado de PD-L1, con al menos 1 y no más de 2 líneas previas de tratamiento antineoplásico sistémico para la enfermedad localmente avanzada/metastásica.
    a)Las localizaciones anatómicas aptas del tumor primario son la orofaringe, la cavidad bucal, la hipofaringe y la laringe.
    b)La localización anatómica del tumor primario no puede ser la nasofaringe (cualquier subtipo histológico).
    E.4Principal exclusion criteria
    All Patients:
    1) Prior radiation therapy (or other nonsystemic therapy) within 2 weeks prior to enrollment
    2) Patient has not fully recovered (ie, ≤ Grade 1 at baseline) from AEs due to a previously administered treatment.
    a) Note: Patients with ≤ Grade 2 neuropathy, ≤ Grade 2 alopecia, or laboratory values in inclusion criteria 5 through 8 are exceptions to this criterion and may qualify for the study.
    b) Note: If a patient received major surgery, he or she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
    3) Positive serum pregnancy test
    4) Breastfeeding female
    5) Active central nervous system (CNS) disease (patients with asymptomatic and stable, treated CNS lesions who have been off corticosteroids, radiation, or other CNS-directed therapy for at least 4 weeks are not considered active)
    6) Red blood cell (RBC) transfusion dependence, defined as requiring more than 2units of packed RBCl transfusions during the 4-week period prior to screening. RBC transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criterion.
    7) History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3months
    8) Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
    9) Prior treatment with cluster of differentiation 47 or signal regulatory protein alpha-targeting agents
    10) Prior anticancer therapy including, but not limited to, chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab treatment
    11) Life expectancy of less than 3 months and/or rapidly progressing disease (eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator
    12) Diagnosis of immunodeficiency or receipt of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy. Corticosteroid use as a premedication for allergic reactions or for prophylactic management of AEs related to the chemotherapies specified in the protocol is allowed. The use of physiologic doses of corticosteroids may be approved with approval by the sponsor.
    13) Active autoimmune disease that has required systemic treatment in the past 2 years (ie, use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
    14) Prior allogeneic tissue/solid organ transplant
    15) History of (noninfectious) pneumonitis that required steroids or current pneumonitis
    16) Active, uncontrolled infection or infection requiring systemic therapy within ≤ 7 days of study entry
    17) Live vaccine within 30 days of start of study treatment
    18) Current participation in another interventional clinical study
    19) Known inherited or acquired bleeding disorders
    20) Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.
    21) Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which patients are not on active anticancer therapies and who are in complete remission for over 5 years
    22) Known HIV infection. HIV testing will be performed at screening only if required by local guidelines or institutional standards.
    23) Known positivity for hepatitis B or C infection. Patients not currently on antiviral therapy and who have an undetectable viral load in the prior 3 months may be eligible for the study. Hepatitis B or C testing is not required. Patients with serologic evidence of prior vaccination to HBV (ie, hepatitis B surface antigen negative and antibody against hepatitis B surface antigen positive) may participate.

    Safety Run-in Cohort 1, Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab (if Applicable), and Phase 2 Cohorts 1 and 2:
    24) Progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC
    25) Prior treatment with any of the following:
    a) Anti–programmed cell death protein 1 or anti–PD-L1 checkpoint inhibitors
    b) Anti–cytotoxic T-lymphocyte–associated protein 4 checkpoint inhibitors
    c) 5-FU and platinum-based chemotherapy (Safety Run-in Cohort 1 and Phase 2 Cohort 1 only)
    Safety Run-in Cohort 2 and Phase 2 Cohort 3:
    26) Progressive disease within 6 months of completion of curatively intended systemic treatment for locally advanced/mHNSCC
    27) Prior treatment with a taxane
    Todos los pacientes
    1)Radioterapia previa (u otro tratamiento no sistémico) en las 2 semanas anteriores a la inclusión.
    2)Recuperación incompleta de los AA (es decir, grado ≤1 al inicio) debidos a un tratamiento administrado previamente.
    a)Nota: los pacientes con neuropatía de grado ≤ 2, alopecia de grado ≤2 o valores analíticos en los criterios de inclusión del 5 al 8 son excepciones a este criterio y pueden ser aptos para el estudio.
    b)Nota: si un paciente se ha sometido a una intervención de cirugía mayor, debe haberse recuperado debidamente de la toxicidad y/o de las complicaciones de la intervención antes de iniciar el tratamiento.
    3)Prueba de embarazo en suero positiva.
    4)Mujer en periodo de lactancia.
    5)Enfermedad del sistema nervioso central (SNC) activa (los pacientes con lesiones del SNC tratadas, asintomáticas y estables que no hayan recibido corticoesteroides, radioterapia ni otro tratamiento dirigido al SNC durante un mínimo de 4 semanas no se consideran pacientes con enfermedad activa).
    6)Dependencia de transfusiones de eritrocitos, definida como la necesidad de más de 2 unidades de transfusiones de concentrado de eritrocitos durante el periodo de 4 semanas previo a la selección. Las transfusiones de eritrocitos están permitidas durante el periodo de selección y antes de la inclusión para satisfacer el criterio de inclusión relativo a la hemoglobina.
    7)Antecedentes de anemia hemolítica, trombocitopenia autoinmunitaria o síndrome de Evans en los últimos 3 meses.
    8)Hipersensibilidad conocida a alguno de los fármacos del estudio, los metabolitos o los excipientes de la formulación.
    9)Tratamiento previo con fármacos dirigidos a CD47 (grupo de diferenciación 47) o a SIRPα (proteína reguladora de señales α).
    10)Tratamiento antineoplásico previo, entre otros, quimioterapia, inmunoterapia o fármacos en investigación, en las 4 semanas anteriores al tratamiento con magrolimab.
    11)Esperanza de vida inferior a 3 meses y/o enfermedad de progresión rápida (p. ej., hemorragia tumoral, dolor tumoral no controlado) en opinión del investigador responsable del tratamiento.
    12)Diagnóstico de inmunodeficiencia o tratamiento con corticoesteroides sistémicos o cualquier otra forma de tratamiento inmunodepresor en los 7 días previos a la primera dosis del tratamiento del estudio. Se permite el uso de corticoesteroides como premedicación frente a las reacciones alérgicas o para el tratamiento profiláctico de los AA debidos a las quimioterapias especificadas en el protocolo. El uso de dosis fisiológicas de corticoesteroides puede aceptarse con la aprobación del promotor.
    13)Enfermedad autoinmunitaria activa que haya requerido tratamiento sistémico en los últimos 2 años (es decir, uso de fármacos modificadores de la enfermedad, corticoesteroides o inmunodepresores). El tratamiento de reposición (p. ej., tiroxina, insulina, corticoesteroides en dosis fisiológicas para la insuficiencia suprarrenal o hipofisaria) no se considera una forma de tratamiento sistémico.
    14)Alotrasplante previo de tejido/víscera maciza.
    15)Antecedentes de neumonitis (no infecciosa) que necesitó corticoesteroides o neumonitis en curso.
    16)Infección activa no controlada o infección que requiera tratamiento sistémico en un plazo ≤7 días antes de la incorporación al estudio.
    17)Administración de una vacuna elaborada con microbios vivos en los 30 días previos al inicio del tratamiento del estudio.
    18)Participación en curso en otro estudio clínico de intervención.
    19)Trastornos hemorrágicos conocidos, hereditarios o adquiridos.
    20)Enfermedad o afecciones médicas significativas, según la evaluación del investigador y del promotor, que perjudicarían sustancialmente la relación riesgo-beneficio de la participación en el estudio. Por ejemplo, infarto agudo de miocardio en los últimos 6 meses, angina inestable, diabetes mellitus no controlada, infecciones activas significativas e insuficiencia cardíaca congestiva de la clase III-IV según la Asociación de Cardiología de Nueva York
    21)Segunda neoplasia maligna, excepto carcinomas tratados basocelulares o espinocelulares localizados, cáncer de próstata localizado u otras neoplasias malignas para las que los pacientes no estén recibiendo tratamientos antineoplásicos activos y que hayan estado en remisión completa durante más de 5 años.
    22)Infección conocida por VIH. Las pruebas del virus de inmunodeficiencia humana se realizarán en selección solo si lo requieren las directrices locales o normas del centro.
    23)Positividad conocida para infección por virus hepB o C. Los pacientes que no estén recibiendo tratamiento antiviral y que hayan tenido carga vírica indetectable en 3 meses anteriores podrían ser aptos para estudio. Las pruebas hepB o C no son necesarias. Pueden participar los pacientes con indicios serológicos de vacunación previa contra el virus hepB (es decir, negativo para el antígeno de superficie del virus de la hepatitis B y positivo para anticuerpos contra este).
    E.5 End points
    E.5.1Primary end point(s)
    Safety Run-in Cohorts:
    Incidence of adverse events (AEs) and laboratory abnormalities defined as dose-limiting toxicities (DLTs) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0

    Phase 2 Cohorts:
    - PFS, defined as the time from the date of randomization until the earliest date of documented disease progression, as assessed by independent central review, or death from any cause, whichever occurs first (Phase 2 Cohort 1)
    - ORR, defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) as measured by response evaluation criteria in solid tumors (RECIST), version 1.1, as determined by investigator assessment (Phase 2 Cohorts 2 and 3)
    Cohortes de preinclusión de seguridad:
    •Incidencia de acontecimientos adversos (AA) y anomalías analíticas definidas como toxicidades limitantes de la dosis (TLD) de acuerdo con los Criterios Terminológicos Comunes para Acontecimientos Adversos (Common Terminology Criteria for Adverse Events, CTCAE) del Instituto Nacional del Cáncer estadounidense (National Cancer Institute, NCI), versión 5.0
    Cohortes de fase 2:
    •SSP, definida como el tiempo transcurrido desde la fecha de aleatorización hasta la fecha de documentación de la progresión de la enfermedad evaluada mediante revisión central independiente o la muerte por cualquier causa, lo que suceda antes (cohorte 1 de fase 2)
    •TRO, definida como la proporción de pacientes que logran una respuesta completa (RC) o una respuesta parcial (RP) determinada mediante la evaluación del investigador conforme a los Criterios de Evaluación de la Respuesta en Tumores Sólidos (Response Evaluation Criteria in Solid Tumors, RECIST), versión 1.1 (cohortes 2 y 3 de fase 2)
    E.5.1.1Timepoint(s) of evaluation of this end point
    The incidence of Adverse events is assessed for the duration of the study at every visit after the first dose of study treatment through 30 days after the last dose of study treatment. Clinical laboratory tests are carried out at most study visits, following the Schedule of Assessments within the protocol. .

    To assess efficacy, clinical and radiographic results are collected at screening, every 6 weeks (2 cycles) until Cycle 12 and then every 9 weeks (3 cycles) during the study, and at the end-of-treatment visit. For Phase 2 Cohort 1, the primary efficacy endpoint will be PFS by independent central review. For Phase 2 Cohorts 2 and 3, assessment of response will be measured by RECIST, version 1.1, as determined by investigator assessment (primary efficacy endpoint).
    La incidencia de AA sera evaluada durante el estudio en cada visita después de primera dosis de tratamiento del estudio hasta 30 días después de ultima dosis de tratamiento del estudio. Se realizaran análisis de laboratorio en la mayoría de visitas según tabla procedimientos del protocolo.
    Para evaluar la eficacia, se recogerán resultados clínicos y radiográficos durante periodo selección, cada 6 sems (2 ciclos) hasta el Ciclo 12 y después cada 9 sems (3 ciclos) durante el estudio y en visita final tratamiento. En cohortes 1 de fase 2, el criterio de valoración principal sera TRO determinado mediante revision central independiente. Para fase 2 cohortes 2 y 3, la evaluación de respuesta sera conforme criterios RECIST, v1.1, según evaluación investigador (criterio evaluación principal).
    E.5.2Secondary end point(s)
    Safety Run-in Cohorts:
    Magrolimab concentration versus time and antidrug antibodies (ADAs) to magrolimab

    Phase 2 Cohorts:
    - ORR, as determined by independent central review
    - PFS from date of randomization (Phase 2 Cohort 1) or date of dose initiation (Phase 2 Cohorts 2 and 3) until the earliest date of documented disease progression as determined by investigator assessment per RECIST, version 1.1, or death from any cause, whichever occurs first
    - DOR, defined as time from first documentation of CR or PR to the earliest date of documented disease progression or death from any cause, whichever occurs first
    - OS, defined as time from date of randomization (Phase 2 Cohort 1) or date of dose initiation (Phase 2 Cohorts 2 and 3) to death from any cause
    - Magrolimab concentration versus time and ADAs to magrolimab
    - PRO assessment (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire [EORTC QLQ-C30], European Organisation for Research and Treatment of Cancer Quality of Life - Head and Neck Module [EORTC QLQ-H&N35], and 5-level EuroQol 5 dimensions questionnaire [EQ-5D-5L]) scores
    Cohortes de preinclusión de seguridad:
    •Concentración de magrolimab frente al tiempo y anticuerpos contra el fármaco (ACF) dirigidos a magrolimab
    Cohortes de fase 2:
    •TRO determinada mediante revisión central independiente
    •SSP desde la fecha de aleatorización (cohorte 1 de fase 2) o la fecha de inicio de la dosis (cohortes 2 y 3 de fase 2) hasta la fecha de documentación de progresión de la enfermedad de acuerdo con la evaluación del investigador conforme a los criterios RECIST, versión 1.1, o la muerte por cualquier causa, lo que suceda antes
    •DR, definida como el tiempo transcurrido desde la primera documentación de la RC o RP hasta la fecha de la documentación de la progresión de la enfermedad o la muerte por cualquier causa, lo que suceda antes
    •SG, definida como el tiempo transcurrido desde la fecha de aleatorización (cohorte 1 de fase 2) o la fecha de inicio de la dosis (cohortes 2 y 3 de fase 2) hasta la muerte por cualquier causa
    •Concentración de magrolimab frente al tiempo y ACF dirigidos a magrolimab
    •Puntuación en las evaluaciones de RNP: cuestionario de calidad de vida de la Organización Europea para la Investigación y el Tratamiento del Cáncer (European Organisation for Research and Treatment of Cancer Quality of Life, EORTC), módulo básico (QLQ-C30); cuestionario de calidad de vida de la EORTC, módulo para cáncer de cabeza y cuello (QLQ-H&N35); y cuestionario EuroQol de 5 dimensiones y 5 niveles (EQ-5D-5L)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Magrolimab concentrations and peripheral blood for immunogenicity assessments for ADAs will be assessed approximately once a cycle until study discontinuation, , according to the Schedule of Assessments within the protocol.

    To assess efficacy, clinical and radiographic results are collected at screening, every 6 weeks (2 cycles) until Cycle 12 and then every 9 weeks (3 cycles) during the study, and at the end-of-treatment visit. For Phase 2 Cohorts 2 and 3, assessment of response will be measured by RECIST, version 1.1, as determined by independent central review (secondary efficacy endpoint). Survival follow-up is carried out every 2 months after safety follow-up visit until death or end of study. PRO assessment scores are collected at every cycle until the last dose of treatment.
    Las concentraciones de magrolimab y de sangre periférica para evaluaciones de inmunogenicidad ACF serán evaluados aprox 1 vez cada ciclo hasta descontinuación del estudio según tabla procedimientos protocolo.
    Para evaluar eficacia, se recogerán resultados clínicos y radiográficos durante periodo selección, cada 6 sems (2 ciclos) hasta ciclo 12 y después cad 9 sems (3 ciclos) durante estudio y en visita final tratamiento. En cohortes 2 y 3 fase 2, la respuesta se determinará mediante criterios RECIST v1.1., conform revision central independiente (criterio valoración secundario eficacia) Seguimiento supervivencia, cada 2 meses después visita seguimiento seguridad hasta final estudio o muerte. Las puntuaciones de RNP se recogerán en cada ciclo hasta ultima dosis tratam.
    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 Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    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 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 trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA33
    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
    Australia
    Belgium
    France
    Germany
    Hong Kong
    Poland
    Portugal
    Spain
    United Kingdom
    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
    Last patient last visit
    Ultimo paciente ultima visita
    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 months3
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days6
    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: 93
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 140
    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 state27
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 110
    F.4.2.2In the whole clinical trial 233
    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)
    None
    Ninguno
    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 Decision2021-12-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-12-17
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA