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    Summary
    EudraCT Number:2017-004188-11
    Sponsor's Protocol Code Number:MK-3475-789
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-10-06
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2017-004188-11
    A.3Full title of the trial
    A Randomized, Double-Blind, Phase 3 Study of Pemetrexed + Platinum Chemotherapy with or without Pembrolizumab (MK-3475) in TKI-resistant EGFR-mutated Tumors in Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Participants (KEYNOTE-789)
    Studio randomizzato, in doppio cieco, di fase 3 di pemetrexed + chemioterapia a base di platino con o senza pembrolizumab (MK-3475) per pazienti con tumore al polmone non a piccole cellule metastatico con mutazione EGFR e resistenza ai TKI (KEYNOTE-789)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 3 Study of Pemetrexed + Platinum Chemotherapy with or without Pembrolizumab (MK-3475) in TKI-resistant EGFR-mutated Tumors in Metastatic Non-Squamous NSCLC
    Studio di fase 3 di pemetrexed + chemioterapia a base di platino con o senza pembrolizumab (MK-3475) in tumori al polmone non a piccole cellule metastatico con mutazione EGFR e resistenza ai TKI (KEYNOTE-789)
    A.3.2Name or abbreviated title of the trial where available
    Pemetrexed+Platinum Chemotherapy with/ without MK-3475 in TKI-resistant EGFR-mutated Tumors in NSCLC
    Pemetrexed + chemioterapia a base di platino con o senza MK-3475 in tumori al polmone non a piccole
    A.4.1Sponsor's protocol code numberMK-3475-789
    A.5.4Other Identifiers
    Name:-Number:-
    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 SponsorMERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. 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 supportMerck Sharp&Dohme Corp,subsidiary Merck&Co,Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMSD Italia srl
    B.5.2Functional name of contact pointDivisione ricerca clinica
    B.5.3 Address:
    B.5.3.1Street AddressVia Vitorchiano ,151
    B.5.3.2Town/ cityRoma
    B.5.3.3Post code00189
    B.5.3.4CountryItaly
    B.5.4Telephone number+390636191371
    B.5.5Fax number+390636380371
    B.5.6E-mailgcto.italy@merck.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 namePembrolizumab
    D.3.2Product code MK-3475
    D.3.4Pharmaceutical form 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.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.3Other descriptive name-
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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) Yes
    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 ALIMTA (PEMETREXED DISODIUM)
    D.2.1.1.2Name of the Marketing Authorisation holderEli Lilly Nederland 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.3.4Pharmaceutical form Powder 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 INNPEMETREXED DISODIUM
    D.3.9.1CAS number 150399-23-8
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive name-
    D.3.9.4EV Substance CodeSUB03669MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 3
    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 ALIMTA (PEMETREXED DISODIUM)
    D.2.1.1.2Name of the Marketing Authorisation holderEli Lilly Australia Pty Limited
    D.2.1.2Country which granted the Marketing AuthorisationAustralia
    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.3.4Pharmaceutical form Lyophilisate for 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 INNPEMETREXED DISODIUM
    D.3.9.1CAS number 150399-23-8
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive namePEMETREXED DISODIUM
    D.3.9.4EV Substance CodeSUB03669MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 Cisplatino
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical 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 INNCISPLATINO
    D.3.9.1CAS number 15663-27-1
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive name-
    D.3.9.4EV Substance Code15663-27-1
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 Carboplatino-Actavis
    D.2.1.1.2Name of the Marketing Authorisation holderActavis Group PTC ehf.
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical 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 INNCARBOPLATINO
    D.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive name-
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 Carboplatino
    D.2.1.1.2Name of the Marketing Authorisation holder-
    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.3.4Pharmaceutical 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.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor code-
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 7
    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 Cisplatino
    D.2.1.1.2Name of the Marketing Authorisation holder-
    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.3.4Pharmaceutical 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.3.9.1CAS number 15663-27-1
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive name-
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 8
    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 Pemetrexed
    D.2.1.1.2Name of the Marketing Authorisation holder-
    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.3.4Pharmaceutical form Lyophilisate for 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 INNPemetrexed disodium
    D.3.9.1CAS number 150399-23-8
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive namePemetrexed disodium
    D.3.9.4EV Substance CodeSUB03669MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic Non-squamous Non-small Cell Lung Cancer
    Carcinoma polmonare non a piccole cellule non squamoso metastatico
    E.1.1.1Medical condition in easily understood language
    Lung cancer (non-small cell lung cancer)
    Carcinoma polmonare (carcinoma polmonare non a piccole cellule)
    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 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    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
    - To compare PFS per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) based on blinded independent central review (BICR) of the combinations of pembrolizumab + chemotherapy versus saline placebo + chemotherapy
    - To compare overall survival (OS) of the combinations of pembrolizumab + chemotherapy versus saline placebo + chemotherapy
    -Confrontare la PFS in base alla revisione centrale indipendente in cieco (BICR) secondo i criteri di valutazione della risposta nei tumori solidi 1.1 (RECIST 1.1) delle combinazioni di pembrolizumab+ chemioterapia rispetto a placebo soluzione salina +chemioterapia
    -Confrontare la sopravvivenza complessiva (OS) delle combinazioni di pembrolizumab + chemioterapia rispetto a placebo di soluzione salina + chemioterapia
    E.2.2Secondary objectives of the trial
    - To compare objective response rate (ORR) per RECIST 1.1 based on BICR of the combinations of pembrolizumab + chemotherapy versus saline placebo + chemotherapy
    - To compare duration of response (DOR) of the combinations of pembrolizumab + chemotherapy versus saline placebo + chemotherapy
    - To evaluate the patient reported outcomes (PROs) mean score changes from baseline to weeks 12 and 27 in global health status and quality of life scale between pembrolizumab + chemotherapy versus saline placebo + chemotherapy
    - To evaluate the PROs time to true deterioration (TTD) in the composite endpoint of cough, chest pain or dyspnea between pembrolizumab + chemotherapy versus saline placebo + chemotherapy
    - To evaluate the safety and tolerability of the combination of pembrolizumab + chemotherapy and saline placebo + chemotherapy
    -Confrontare il tasso di risposta obiettiva (ORR) in base alla BICR secondo i criteri RECIST 1.1
    delle combinazioni di pembrolizumab +chemioterapia rispetto a placebo di soluzione
    salina + chemioterapia.
    -Confrontare la DOR (durata della risposta) delle combinazioni di pembrolizumab + chemioterap
    rispetto a placebo di soluz salina+chemioterap
    -Confrontare le variazioni medie del punteggio relativo agli esiti riferiti dal paziente (PRO) dal basale alle Settimane 12e27 relativi alla scala dello stato di salute globale e della qualit¿ della vita tra pembro+ chemioterap rispetto a placebo di soluz salina+chemioterap.
    -Confrontare il tempo a vero peggioramento (TTD) dei PRO nell¿endpoint composito di tosse, dolore toracico o dispnea tra pembro +chemioterap rispetto a placebo di soluz salina + chemioter
    -Valutare la sicurez e la tollerab della combinazione di pembro + chemio e placebo di soluz salina+ chemioter
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Other types of substudies
    Specify title, date and version of each substudy with relative objectives: Merck will conduct Future Biomedical Research on DNA (Blood,serum/plasma and tissue)specimens collected during this clinical trial.Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects.The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer,more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Merck condurr¿ una Ricerca Biomedica Futura su campioni di DNA (estratti da sangue,siero/plasma e tessuto) raccolti nel corso di questo studio clinico. Tale ricerca ha lo scopo di esaminare vari biomarcatori per rispondere a domande che stanno emergendo e che non sono descritte in altre parti del protocollo (nell'ambito dello studio principale), e verr¿ condotta solo su campioni di soggetti che abbiano espresso il proprio consenso in maniera specifica per questa ricerca. L'obiettivo della raccolta dei campioni per la Ricerca Biomedica Futura ¿ quello di esplorare e identificare biomarcatori che contribuiscano scientificamente alla comprensione delle malattie e/o delle relative terapie. L'obiettivo ultimo ¿ quello di utilizzare tali informazioni per sviluppare farmaci pi¿ sicuri e pi¿ efficaci, e/o per garantire che i soggetti ricevano la dose giusta del giusto farmaco al momento giusto.
    E.3Principal inclusion criteria
    1. Have histologically or cytologically confirmed diagnosis of Stage IV (AJCC Version 8 or current version as applicable) non-squamous NSCLC
    2. Have documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R
    3. Have investigator determined radiographic disease progression per RECIST 1.1 after treatment with an EGFR TKI therapy:
    a) Participants previously treated with 1st or 2nd generation EGFR TKI (eg, erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation
    b) Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (eg, erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment
    c) Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status
    4. Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
    5. Have provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archival tissue
    6. Be =18 years of age on the day of signing informed consent
    7. Have a life expectancy of at least 3 months
    8. Have an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization
    9. A male participant must agree to use contraception as detailed in protocol Section 10.3 during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after last dose of chemotherapeutic agents
    10. A female participant is eligible to participate if she is not pregnant (see protocol Section 10.3), not breastfeeding, and at least one of the following conditions applies:
    a. Not a woman of childbearing potential (WOCBP) as defined in protocol Appendix 3
    OR
    b. A WOCBP who agrees to follow the contraceptive guidance in protocol Section 10.3 during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents
    11. The participant provides written informed consent for the study
    12. Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of trial treatment
    1.Diagnosi istologicamente o citologicamente confermata di NSCLC non squamoso in stadio IV (AJCC Versione 8 o versione attuale, come applicabile).2.Presenza documentata di mutazione tumorale attivante di EGFR, nello specifico DEL19 o L858R.3.Progressione radiologica della malattia determinata dallo sperimentatore secondo i criteri RECIST 1.1dopo trattamento con una terapia a base di EGFR TKI:a)I partecipanti precedentemente trattati con un EGFR TKI di prima o seconda generazione (per es., erlotinib/afatinib/gefitinib) devono presentare assenza documentata confermata della mutazione EGFR T790M.b)I partecipanti con positività confermata per la mutazione T790M acquisita dopo trattamento con un EGFR TKI di prima o seconda generazione (per es.,erlotinib/afatinib/gefitinib)devono presentare fallimento del trattamento con il TKI osimertinib prima dell’arruolamento.c)I partecipanti con precedente fallimento del trattamento con il TKI osimertinib somministrato come terapia di prima linea sono eleggibili a prescindere dallo stato della mutazione EGFR T790M.4.Malattia misurabile secondo i criteri RECIST 1.1, come valutata dallo sperimentatore/dal servizio di radiologia del centro locale.Le lesioni localizzate in un’area precedentemente irradiata sono considerate misurabili se ne è stata dimostrata la progressione.5.Disponibilità di un campione di tessuto tumorale archiviato o di una biopsia incisionale o escissionale ottenuta ex-novo (nessuna terapia antineoplastica dopo la biopsia) da una lesione tumorale non precedentemente irradiata.I blocchetti di tessuto fissati in formalina e inclusi in paraffina (formalin-fixed, paraffin embedded, FFPE)sono preferibili rispetto ai vetrini.Le biopsie ottenute ex-novo sono preferibili rispetto al tessuto archiviato.6. Età =18 anni alla data di firma del consenso informato. 7. Aspettativa di vita pari almeno a 3 mesi. 8. Stato di validità ECOG di 0 o 1 entro 7 giorni prima della prima dose di trattamento dello studio ma prima della randomizzazione. 9. Un partecipante di sesso maschile deve acconsentire all’uso di metodi contraccettivi come descritto nella Sezione 10.3 del protocollo durante il periodo di trattamento e per almeno 120 giorni dopo l’ultima dose di pembrolizumab e fino a 180 giorni dopo l’ultima dose degli agenti chemioterapici. 10. Una partecipante di sesso femminile è eleggibile alla partecipazione qualora non sia in stato di gravidanza (vedere Sezione 10.3 del protocollo), non stia allattando e soddisfi almeno una delle seguenti condizioni: a. non sia una donna in età fertile (woman of childbearing potential, WOCBP) come da definizione fornita nell’Appendice 3 del protocollo dello studio; oppure b. sia una WOCBP che accetta di attenersi alle indicazioni sui metodi contraccettivi di cui alla Sezione 10.3 del protocollo dello studio durante il periodo di trattamento e per almeno 120 giorni dopo l’ultima dose di pembrolizumab e fino a 180 giorni dopo l’ultima dose degli agenti chemioterapici. 11. Il partecipante fornisce consenso informato scritto per lo studio. 12. Funzionalità d’organo adeguata, come definita nel protocollo. I campioni devono essere prelevati entro 10 giorni prima dell’avvio del trattamento dello studio.
    E.4Principal exclusion criteria
    1. Has predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible
    2. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
    3. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization (see protocol Section 10.3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
    4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
    5. Has received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC
    6. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system (CNS) disease
    7. Has received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), 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 (eg, FluMist®) are live attenuated vaccines and are not allowed
    8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
    9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
    10. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
    11. Has known active untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
    12. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients
    13. Has a known sensitivity to any component of cisplatin, carboplatin, or pemetrexed
    14. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
    15. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
    16. Has an active infection requiring systemic therapy
    17. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
    18. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive or HBV-DNA detected) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infection
    19. Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
    20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
    21. Has known psychiatric or substance abuse disorder that would interfere with cooperating with the requirements of the study
    22. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents
    1. NSCLC con istologia a predominanza di cell squamose. I tumori misti verranno classificati in base al tipo cell predominante; se sono presen elementi a piccole cell, il partecip non è eleggibile. 2. Ascite o versamento pleurico sintomat. Un partecip clinicam stabile dopo trattam per queste condiz (compresa la toracentesi o la paracentesi terapeutica) è eleggibile. 3. WOCBP con test di gravid sulle urine posit entro 72 h prima della randomizzaz (vedi la Sez 10.3). In caso di test sulle urine posit o la cui negatività non possa essere confermata, sarà richiesto un test di gravid sul siero. 4.Preceden terap con un agente anti-PD-1, anti-PD-L1 o anti-PD-L2 o con un agente diretto contro un altro recett stimolante o co-inibith delle cell T (per es. CTLA-4, OX-40, CD137). 5.Preceden chemioterap citotossica sistemica o trattam con uno o più agenti sperimentali, esclusi gli EGFR TKI,per NSCLC metastat. 6. Preceden radioterap entro 2 sett dall’avvio del trattam dello stu. I partecipanti devono essersi ristabiliti da tutte le tossicità correlate alla radioterap, non necessitare di corticosteroidi e non presentare polmonite da radiazioni. È consentito un washout di 1 settimana per la radioterap palliativa (=2 sett di radioterap) su malattia non del sistema nervoso centrale (SNC). 7. Ricevimento di un vaccino vivo entro 30 giorni prima della prima dose di trattam dello stu. Esempi di vaccini vivi comprendono, in modo non limitativo: morbillo, parotite, rosolia, varicella/zoster, febbre gialla, rabbia, bacillo di Calmette-Guérin (BCG) e vaccino tifoideo. I vaccini per l’influenza stagionale somministrati per iniezione in genere sono vaccini a virus uccisi e sono ammessi; tuttavia, i vaccini antinfluenzali intranasali (per es., Flu-Mist®) sono vaccini vivi attenuati e non sono consentiti. 8.Partecipaz in corso o pregressa a uno stu su un agente sperimentale o utilizzo di un disposit sperimentale entro 4 sett prima della prima dose di trattam dello stu. 9. Diagnosi di immunodeficienza o trattam in corso con terap steroidea sistemica cronica (a dosi superiori a 10 mg al giorno di un equivalente del prednisone) o qls altra forma di terap immunosoppressiva entro 7 giorni prima della prima dose di trattam dello stu. 10. Presenza di un’ulterih malignità nota che è progredita o ha richiesto un trattam attiv negli ultimi 5 anni.11. Metastasi attiv note al SNC non sottoposte a trattam e/o meningite carcinomatosa. I partecipanti con metastasi cerebrali precedenmente trattate possono partecipare a condizione che siano radiologicamente stabili, ovvero, senza evidenza di progressione per almeno 4 sett in base a ripetute valutaz di imaging (si noti che le valutaz di imaging devono essere ripetute durante lo screening dello stu), clinicam stabili e senza necessità di trattam steroideo per almeno 14 giorni prima della prima dose di trattam dello stu.12. Ipersensibilità grave (grado =3) a pembrolizumab e/o a uno qls degli eccipienti. 13. Sensibilità nota a qls componente di cisplatino, carboplatino o pemetrexed. 14. Malattia autoimmune in fase attiva che abbia richiesto un trattam per via sistemica negli ultimi 2 anni (ovvero, con impiego di agenti modificanti la malattia, corticosteroidi o farmaci immunosoppressori). La terap sostitutiva (per es., tiroxina, insulina o terap sostitutiva con dosi fisiologiche di corticosteroidi per insufficienza surrenalica o pituitaria) non è considerata una forma di trattam sistemico ed è consentita.15. Anamnesi di polmonite (non infettiva) che abbia richiesto l’uso di steroidi o polmonite in atto. 16. Infezione attiva con necessità di terap sistemica. 17. Anamnesi nota di infezione da virus dell’immunodeficienza umana (HIV). Salvo se richiesto dall’autorità sanitaria locale, non è necessario eseguire il test per l’HIV.18. Anamnesi nota di epatite B (definita come reattività all’antigene di superficie dell’epatite B HBsAg o rilevabilità dell’HBV-DNA) o infezione attiva nota da virus dell’epatite C (definita come rilevabilità [qualitativa] dell’HCV-RNA o reattività agli anticorpi anti-HCV, se la ricerca dell’HCV RNA non rientra nello standard di cura [SOC] locale). 19. Anamnesi nota di tubercolosi (TB; Bacillus tuberculosis) attiva. 20. Anamnesi o attuale evidenza di qls condizione, terap o anomalia di laboratorio che potrebbe confondere i risultati dello stu, interferire con la partecip del sogg per tutta la durata dello stu o far ritenere tale partecip non nel miglior interesse del sogg, secondo l’opinione dello sperimentath responsabile del trattam.21. Disturbo noto di natura psichiatrica o da abuso di sostanze che potrebbe interferire con l’osservanza dei requisiti dello stu. 22. Partecip in stato di gravid o allattamento o che prevede di concepire o generare figli entro la durata prevista dello stu, a partire dalla visita di screening fino a 120 giorni dopo l’ultima dose di pembrolizumab e fino a 180 giorni dopo l’ultima dose degli agenti chemioterapici
    E.5 End points
    E.5.1Primary end point(s)
    1) Progression-free Survival (PFS) per RECIST 1.1 assessed by BICR
    2) Overall survival (OS)
    1)Sopravvivenza libera da progressione (PFS)valutata in base alla revisione centrale indipendente in
    cieco (BICR) secondo i Criteri di valutazione della risposta nei tumori solidi (RECIST) 1.1
    2)Sopravvivenza complessiva
    E.5.1.1Timepoint(s) of evaluation of this end point
    - 34 weeks after the last participant has been randomized (estimated approximately 372 PFS events across two treatment groups have been observed)
    - Final PFS analysis: when least 12 months after the last participant has been randomized AND at least 414 PFS events have been observed (estimated~32 months after the first participant randomized)
    - Final OS analysis: To be performed every 8 to 9 months until at least 30months after the last participant has been randomized AND at least ~360 deaths have occurred for the final OS analysis (estimated ~59 months after the first participant randomized)
    - 34 settimane dopo la randomizzazione dell’ultimo partecipante (in base alle stime, dopo l’osservazione di circa 372 eventi di PFS nell’ambito dei due gruppi di trattamento)
    -analisi finale della PFS: da eseguire almeno 12 mesi dopo la randomizzazione dell’ultimo partecipante E una volta osservati almeno 414 eventi di PFS nell’ambito dei due gruppi di trattamento (in base alle stime, ~32 mesi dopo la randomizzazione del primo partecipante).
    - Analisi finale dell'OS:da eseguire ogni 8-9 mesi fino ad almeno 30 mesi dopo la randomizzazione dell’ultimo partecipante E una volta verificatisi almeno ~360 decessi per l’analisi finale dell’OS (in base alle stime, ~59 mesi dopo la randomizzazione del primo partecipante).
    E.5.2Secondary end point(s)
    1) Objective response rate (ORR) per RECIST 1.1 assessed by BICR
    1)Tasso di risposta obiettiva (ORR) in base alla
    BICR secondo i criteri RECIST 1.1
    E.5.2.1Timepoint(s) of evaluation of this end point
    34 weeks after the first 270 participants have been randomized (estimated ~19 months after the first participant randomized)
    -34 settimane dopo la randomizzazione dei primi 270 partecipanti (in base alle stime, ~19 mesi dopo la randomizzazione del primo partecipante).
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Quality of life patient reported outcomes
    Risultati della qualit¿ della vita dei pazienti
    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 Yes
    E.8.1.7.1Other trial design description
    Crossover fase monoterapica con pembrolizumab
    Crossover phase to pembrolizumab monotherary
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA51
    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 Information not present in EudraCT
    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
    Brazil
    Canada
    China
    France
    Germany
    Hong Kong
    Israel
    Italy
    Japan
    Korea, Republic of
    Mexico
    Spain
    Sweden
    Taiwan
    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
    LVLS
    LVLS
    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 years5
    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: 240
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 240
    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 state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 156
    F.4.2.2In the whole clinical trial 480
    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
    Nessuno
    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 Decision2018-06-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-04-18
    P. End of Trial
    P.End of Trial StatusOngoing
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