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    Summary
    EudraCT Number:2015-000681-55
    Sponsor's Protocol Code Number:MK3475-022
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-01-22
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-000681-55
    A.3Full title of the trial
    A Phase I/II Study to Assess the Safety and Efficacy of MK-3475 in Combination with Trametinib and Dabrafenib in Subjects with Advanced Melanoma
    Studio di Fase I/II per valutare la sicurezza e l'efficacia di MK-3475 in combinazione con trametinib e dabrafenib in soggetti con melanoma avanzato
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase I/II Study of MK-3475 in Combination with Trametinib and Dabrafenib
    Studio di Fase I/II di MK-3475 in combinazione con trametinib e dabrafenib
    A.3.2Name or abbreviated title of the trial where available
    Phase I/II Study of MK-3475 in Combination with Trametinib and Dabrafenib
    Studio di Fase I/II di MK-3475 in combinazione con trametinib e dabrafenib
    A.4.1Sponsor's protocol code numberMK3475-022
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02130466
    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.sussidiaria di 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 nameMK-3475
    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 nameAnti-PD-1 monoclonal antibody
    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 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 Tafinlar
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Ltd
    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 nameDabrafenib
    D.3.2Product code [DRB436]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDABRAFENIB
    D.3.9.1CAS number 1195768-06-9
    D.3.9.2Current sponsor code.
    D.3.9.4EV Substance CodeSUB128623
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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 Tafinlar
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Ltd
    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 nameDabrafenib
    D.3.2Product code [DRB436]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDABRAFENIB
    D.3.9.1CAS number 1195768-06-9
    D.3.9.2Current sponsor code.
    D.3.9.4EV Substance CodeSUB128623
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 Mekinist
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Ltd
    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 nameTrametinib
    D.3.2Product code [TMT212]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTrametinib
    D.3.9.1CAS number 1187431-43-1
    D.3.9.2Current sponsor code.
    D.3.9.4EV Substance CodeSUB119776
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 Mekinist
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Ltd
    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 nameTrametinib
    D.3.2Product code [TMT212]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTrametinib
    D.3.9.1CAS number 1187431-43-1
    D.3.9.2Current sponsor code.
    D.3.9.4EV Substance CodeSUB119776
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0
    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 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.2.1.2Country 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 nameTrametinib
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTrametinib
    D.3.9.1CAS number 1187431-43-1
    D.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB119776
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 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.2.1.2Country 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 nameTrametinib
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTrametinib
    D.3.9.1CAS number 1187431-43-1
    D.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB119776
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(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
    advanced or metastatic melanoma - all parts of the trial
    advanced (unresectable and/or metastatic) solid tumours - Parts 4 and 5
    melanoma avanzato o metastatico per tutte le parti del trial.
    Tumori solidi avanzati (non resecabili e/o metastatici) per parti 4 e 5
    E.1.1.1Medical condition in easily understood language
    advanced or metastatic melanoma - all parts of the trial
    advanced (unresectable and/or metastatic) solid tumours - Parts 4 and 5
    melanoma avanzato o metastatico per tutte le parti del trial.
    Tumori solidi avanzati (non resecabili e/o metastatici) per parti 4 e 5
    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 LLT
    E.1.2Classification code 10053571
    E.1.2Term Melanoma
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10053571
    E.1.2Term Melanoma
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065252
    E.1.2Term Solid tumor
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Parts 1/2: To evaluate the safety/tolerability and identify the MTD/MAD of: (1a) MK-3475 +D/T in subjects with adv. melanoma with BRAF V600E/K mutations (1b) MK-3475 +T in subjects with adv. melanoma without BRAF V600E/K mutations (1c) MK-3475 +D in subjects with adv. melanoma with BRAF V600E mutations. (only if (1a) is not tolerated).
    Part 2: To confirm the safety/tolerability of the preliminary MTD/MAD of:(2) MK-3475 + D/T in subjects with adv. melanoma with BRAF V600E/K mutations (3) MK-3475 + T in subjects with adv. melanoma without BRAF V600E/K mutations (4) To evaluate the efficacy of MK- 3475+T in subjects with adv. melanoma without BRAF V600E/K mutations with respect to Objective Response Rate
    Part 3: (5) To evaluate the efficacy with respect to PFS of MK-3475 in combination with D/T in subjects with adv. melanoma with BRAF V600E/K mutations, compared with placebo + D/T alone D/T: dabrafenib/tremetinib; T: trametinib; D: dabrafenib
    Part 4/5:refer to protocol for details
    Parte 1/2: valutare la sicurezza/tollerabilità e identificare la MTD/ MAD di: (1a) MK-3475 +D/T in soggetti con melanoma avanzato con mutazioni di BRAF V600 E/K. (1b) MK-3475 +T in soggetti con melanoma avanzato senza mutazioni di BRAF V600.(1c) MK-3475 +D in soggetti con melanoma avanzato con mutazioni di BRAF V600 E (solo se 1a) non è tollerato).
    Parte 2: confermare la sicurezza/tollerabilità di MTD/MAD preliminari di: (2) MK-3475 +D/T in soggetti con melanoma avanzato con mutazioni di BRAF V600 E/K. (3) MK-3475 nel melanoma avanzato senza mutazioni di BRAF V600. (4) MK-3475 +T in soggetti con melanoma avanzato senza mutazioni di BRAF V600 rispetto ad ORR.
    Parte 3: (5) valutare l’efficacia rispetto a PFS di MK-3475 +D/T in soggetti con melanoma avanzato con mutazioni di BRAF V600 E/K, rispetto a placebo +D/T.
    Parti 4 e 5: fare riferimento al protocollo per dettagli.
    E.2.2Secondary objectives of the trial
    Part 1 and 2:
    (1) Objective: To evaluate the efficacy of MK-3475 administered intravenously in combination with oral dabrafenib and trametinib in subjects with advanced (unresectable or metastatic) melanoma with BRAF V600 E or K mutations with respect to Objective Response Rate (ORR).
    Parts 1, 2, 3, 4 and 5:
    (2) Objective: To evaluate the pharmacokinetics (PK) of MK-3475, dabrafenib, and/or trametinib when MK-3475 is administered intravenously in combination with oral dabrafenib and/or trametinib.
    Part 3:
    (3) Objective: To evaluate the efficacy of MK-3475 administered intravenously in combination with oral dabrafenib and trametinib in subjects with advanced (unresectable or metastatic) melanoma with BRAF V600 E or K mutations with respect to Objective Response Rate (ORR), Response Duration, and overall survival (OS), compared with oral dabrafenib and trametinib alone.
    Parte 1/2:
    (1) valutare l'efficacia di MK-3475 EV + D/T per via orale in soggetti con melanoma avanzato (non resecabile o metastatico con mutazioni di BRAF V600 E/K rispetto al tasso di risposta obiettiva (ORR).
    Parti 1, 2, 3, 4 e 5:
    (2) valutare la farmacocinetica (PK) di MK-3475, D, e/o T, quando MK-3475 è somministrato EV + D/T per via orale
    Parte 3:
    (3) valutare l'efficacia di MK-3475 EV + D/T per via orale in soggetti con melanoma avanzato (non resecabile o metastatico con mutazioni di BRAF V600 E/K rispetto al tasso di risposta obiettiva (ORR), alla durata della risposta, la sopravvivenza complessiva (OS), rispetto a De T da soli per via orale.
    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 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 condurrà una Ricerca Biomedica Futura su campioni di DNA (estratti dal sangue e da tessuti) 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 verrà condotta solo su campioni di soggetti che abbiano rilasciato apposito consenso. L'obiettivo della raccolta dei campioni per la Ricerca Biomedica Futura è quello di esplorare e identificare biomarcatori che contribuiscano scientificamente alla comprensione delle malattie e/o delle relative terapie. L'obiettivo ultimo è quello di utilizzare tali informazioni per sviluppare farmaci più sicuri e più efficaci, e/o per garantire che i soggetti ricevano la dose giusta del giusto farmaco al momento giusto.
    E.3Principal inclusion criteria
    1. Have a histologically confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma or a histologically or cytologically-documented locallyadvanced or metastatic solid malignancy, and have at least one measurable lesion as defined by RECIST 1.1 on imaging studies (CT or MRI). Cutaneous lesions and other superficial lesions that are detectable only by physical examination and subcutaneous lesions detectable by CT are not considered measurable lesions for the purposes of this protocol, but may be considered as nontarget lesions
    - Mucosal or ocular melanoma are excluded
    - For solid tumors other than melanoma, the subject must be a participant in Part 4 or 5 (dose confirmation only), have a malignancy that is incurable and has either: (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician. There is no limit to the number of prior treatment regimens, but prior treatment(s) should not include compounds targeting PD-1, PD-L1, BRAF, or MEK. Treatment must end at least 4 weeks prior to randomization.
    2. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for FBR. However, the subject may participate in the main trial without participating in FBR
    3. Be >= 18 years of age on day of signing the informed consent
    4.Have BRAF mutation testing as determined at a local laboratory and either:
    a. Have a BRAF mutation-positive (V600 E or K) tumor to be eligible for treatment with pembrolizumab+trametinib+dabrafenib, trametinib+dabrafenib or pembrolizumab+dabrafenib (if this part of the study is performed). If a subject's initial specimen does not test BRAF mutation-positive, a newly obtained specimen (different from the sample previously submitted) may be submitted for testing. If the newer specimen tests BRAF mutationpositive,
    the subject meets this eligibility criterion.
    b. Have a BRAF mutation-negative (wild type) tumor to be eligible for treatment with pembrolizumab+trametinib.
    - Criterion 4a is applicable only to enrollment of melanoma subjects in Parts 1, 2, and 3 of the trial design. Criterion 4b is applicable only to enrollment of melanoma subjects in Parts 1, 2, 4, and 5 of the trial design. The inclusion criterion does not apply to solid tumor subjects in Parts 4 and 5 (dose confirmation only).
    5. For BRAF mutation-negative (wild type) subjects who have received prior therapy for metastatic or advanced melanoma, must have documented progression of at least one measurable lesion by RECIST 1.1 on imaging studies (CT or MRI).
    6. Have a performance status of 0 or 1 on the ECOG Performance Scale
    .........
    11. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the subject to be eligible.
    12. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
    a. Not a woman of childbearing potential (WOCBP)
    OR
    b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study
    treatment.
    Please refer to protocol for the rest of inclusion criteria
    1. Presentare una diagnosi confermata istologicamente di melanoma avanzato (non resecabile di Stadio III) o metastatico (di Stadio IV) e avere almeno una lesione misurabile secondo quanto definito dai criteri RECIST 1.1 sugli studi di diagnostica per immagini (TC o RM). Le lesioni cutanee e altre lesioni superficiali che possono essere rilevate solo da un esame obiettivo e le lesioni sottocutanee rilevabili con TC non sono considerate lesioni misurabili ai fini di questo protocollo, ma possono essere considerate come lesioni non-target.
    - Il soggetto non può avere una diagnosi di melanoma, mucosale od oculare.
    - Per tumori solidi diversi dal melanoma il soggetto deve essere un partecipante della parte 4 o 5 (solamente conferma della dose), avere un tumore incurabile e per il quale:
    a) è fallita una precedente terapia standard, oppure b) non esiste una terapia standard, oppure c) la terapia standard non è considerata appropriata dal paziente e dal medico.
    Non c’è limite di numero di regimi di trattamento precedenti, ma essi non dovrebbero includere composti diretti contro PD-1, PD-L1, BRAF o MEK. Il trattamento deve terminare almeno 4 settimane prima della randomizzazione.
    2. Essere disposto e in grado di fornire un consenso informato scritto alla sperimentazione. Il soggetto può inoltre decidere di fornire il consenso per la ricerca biomedica futura. Tuttavia, il soggetto può partecipare alla sperimentazione principale senza prendere parte alla ricerca biomedica futura.
    3. Avere maggiore= 18 anni il giorno in cui firma il consenso informato.
    4. Avere un’analisi della mutazione di BRAF determinata presso un laboratorio locale e:
    a. Avere un tumore positivo alla mutazione di BRAF (V600 E/K) per essere eleggibile al trattamento con pembrolizumab+trametinib+dabrafenib, trametinib+dabrafenib o pembrolizumab+dabrafenib (se viene effettuata questa parte dello studio). Se il campione iniziale del soggetto non si rivela positivo per la mutazione di BRAF, può essere presentato all’analisi un campione nuovamente prelevato (diverso dal campione presentato precedentemente). Se il nuovo campione si rivela positivo per la mutazione di BRAF, il soggetto risponde ai criteri di eleggibilità.
    b. Avere un tumore negativo alla mutazione di BRAF (wild type) per essere eleggibile al trattamento con pembrolizumab+trametinib.
    - Il criterio 4a si applica solo per l’arruolamento di soggetti con melanoma in parti 1, 2 e 3 del disegno della sperimentazione.Il criterio 4b si applica solo per l’arruolamento delle Parti 1, 2, 3, 4 e 5 del disegno della sperimentazione. Il criterio di inclusione non si applica a soggetti con tumore solido coinvolti nelle parti 4 e 5 (solamente conferma della dose).
    5. I soggetti negativi alla mutazione di BRAF (wild type) che hanno ricevuto una terapia pregressa per melanoma metastatico o avanzato, devono presentare una progressione documentata di almeno una lesione misurabile secondo i criteri RECIST 1.1 sugli studi di diagnostica per immagini (TC o RM).
    6. Avere uno stato di validità di 0 o 1 in base alla scala dello stato di validità dell’Eastern Cooperative Oncology Group (ECOG).
    ........
    11. I soggetti di sesso femminile potenzialmente fertili devono presentare un test di gravidanza sulle urine o sul siero negativo entro 72 ore prima di assumere la prima dose del medicinale in studio. In caso di test sulle urine positivo o non confermato come negativo, sarà richiesto un test di gravidanza sul siero. Il test di gravidanza sul siero deve essere negativo perché il soggetto possa essere considerato eleggibile.
    12. Un soggetto di sesso femminile può partecipare se non è incinta, se non sta allattando al seno e se applica almeno una delle seguenti condizioni:
    a. non è una donna potenzialmente fertile (WOCBP)
    OR
    b. è una WOCBP che utilizza metodi contraccettivi durante il periodo di trattam e fino a 120 giorni dopo l’ultima dose del trattam sperim
    Si prega di fare riferimento al protocollo per i criteri di inclusione rimanenti
    E.4Principal exclusion criteria
    1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
    2. Is either:
    1) BRAF mutation-positive and has received prior systemic therapy for metastatic or advanced melanoma or
    2) BRAF mutation-negative and has received >1 prior systemic therapy for metastatic melanoma. The BRAF exclusion criterion does not apply to solid tumour subjects in Parts 4 and 5 (dose confirmation only).
    3. Has received prior therapy with compounds targeting the PD-1, PD-L1, BRAF, MEK or other molecules in the MAPK pathway.
    4. Is BRAF mutation-positive and has received prior systemic therapy with ipilimumab or other CTLA-4 blocking antibodies.
    5. Has had chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of trial treatment, or who has not recovered to CTCAE Grade 1 or better from the clinically significant AEs due to cancer therapeutics administered more than four weeks prior to the first dose of trial treatment.
    6. Is expected to require any other form of systemic or localized antineoplastic therapy while in study.
    7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy. For dabrafenib-containing treatment regimens in this study, subjects with any malignancy with confirmed activating RAS mutation are excluded.
    8. Has known active central nervous metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are off systemic steroids for at least two weeks.
    9. Has an active infection requiring systemic therapy.
    10. Has an active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from the study.
    11. Has previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
    12. Is on chronic systemic steroid therapy (>10 mg/day prednisone or equivalent) within two weeks before the planned date for first dose of study treatment or on any other form of immunosuppressive medication.
    13. Currently uses a prohibited medication as described in Section 5.5.2.
    14. Has history or evidence of cardiovascular risk. Refer to protocol for the complete list
    15. Has uncorrectable electrolyte abnormalities long QT syndrome or taking medicinal products known to prolong the QT interval.

    Please refer to protocol for the rest of exclusion criteria
    1) Sta partecipando o ha partecipato a uno studio condotto su un agenti sperimentali o tramite l’utilizzo di un dispositivo sperimentale nei 30 giorni dalla prima dose del trattamento sperimentale.
    2) È positivo alla mutazione di BRAF e ha ricevuto una terapia sistemica pregressa per melanoma metastatico o avanzato. Il criterio di esclusione relativo a BRAF non si applica ai soggetti con tumore solido partecipanti alle parti 4 e 5 del trial (solamente conferma della dose).
    3) Ha ricevuto una terapia pregressa con composti diretti verso/contro a PD-1, PD-L1, BRAF, MEK o altre molecole nel percorso MAPK.
    4) È positivo alla mutazione di BRAF e ha ricevuto una terapia sistemica pregressa con ipilimumab o altri anticorpi bloccanti CTLA-4.
    5) Ha ricevuto chemioterapia, radioterapia o terapia antitumorale biologica nelle 4 settimane precedenti la prima dose del trattamento sperimentale, o non è passato al Grado 1 o migliore dei criteri CTCAE dagli AE clinicamente significativi dovuti agli agenti terapeutici antitumorali somministrati più di 4 settimane prima della prima dose del trattamento sperimentale.
    6) È previsto che richieda qualsiasi altra forma di terapia antineoplastica sistemica o localizzata durante lo studio.
    7) Ha un’anamnesi nota di malignità addizionale che sta progredendo o richiede trattamento attivo. Eccezioni includono i tumori a stadi precoci (carcinoma in situ o di stadio 1) trattati con intento curativo, carcinoma della pelle a cellule basali o squamose, carcinoma vescicale superficiale, carcinoma in situ della cervice uterina, carcinoma mammario in situ che è stato sottoposto a terapia potenzialmente curativa Per i regimi di trattamento che contengono dabrafenib in questo studio, sono esclusi i sogg con una malignità qualsiasi con mutazione attivante di RAS.
    8) Presenta metastasi attive note al sistema nervoso centrale (SNC) e/o meningite carcinomatosa. I sogg con metastasi cerebrali già trattate in precedenza possono partecipare purché siano stabili (senza evidenza di progressione alla RM da almeno 4 settimane prima della prima dose del trattamento sperimentale e purché qualsiasi sintomo neurologico sia tornato al valore basale), non abbiano evidenze di metastasi cerebrali nuove o ingrossate e non assumano steroidi sistemici da almeno 2 settimane.
    9) Presenta un’infezione attiva che richiede una terapia per via sistemica.
    10) Presenta una malattia autoimmune attiva, o un’anamnesi documentata di malattia autoimmune, oppure una sindrome che richiede una terap con steroidi sistemici o agenti immunosoppressori. I sogg affetti da vitiligine o asma/atopia risolta nell’infanzia costituiscono un’eccezione a tale regola. I sogg che necessitano di un uso intermittente di broncodilatatori o iniezioni locali di steroidi non saranno esclusi dallo studio. I sogg con ipotiroidismo stabile in terapia di sostituzione ormonale non saranno esclusi dallo studio.
    11) Ha avuto in precedenza una reazione grave di ipersensibilità al trattamento con un altro mAb.
    12) Sta seguendo una terapia steroidea sistemica (> 10 mg/giorno di prednisone o equivalente) nelle 2 sett prima della data prevista per la prima dose del trattamento dello studio o qualsiasi altra forma di medicinale immunosoppressore (i sogg per i quali si prevede una pre-medicazione con corticosteroidi per MK-3475 non saranno eleggibili a questo stud).
    13) Utilizza attualmente un farmaco vietato, come descritto nella Sez 5.5.2 del protocollo.
    14) Presenta un’anamnesi o evidenza di rischio cardiovascolare. Si faccia riferimento al protocollo per la lista completa.
    15) Presenta anomalie elettrolitiche incorreggibili (ad es. ipocaliemia, ipomagnesiemia, ipocalcemia), sindrome da QT prolungato o assume prodotti medicinali noti per prolungare l’intervallo QT.

    Si prega di fare riferimento al protocollo per i criteri di esclusione rimanenti
    E.5 End points
    E.5.1Primary end point(s)
    The primary safety endpoint in Parts 1, 2, 4, and 5 of the study is DLT. In Part 3, there will be no Tier 1 safety endpoints; Tier 2 and Tier 3 safety endpoints will be evaluated as described in 8.2.5.4. Safety will be monitored by cumulative data reviews throughout the trial. The toxicities and grades experienced by subjects who have received study treatment, including adverse events (AEs), serious adverse events (SAEs) and events of clinical interest (ECIs) will be summarized. Other safety measures evaluated in all parts of the study include laboratory
    safety assessments, ECGs, vital signs, and physical examinations.
    The primary efficacy endpoint in Part 3 will be progression-free survival (PFS), and defined as the time from randomization in Part 3 (or the start of treatment in other Parts) to progressive disease (PD) or death, whichever occurs earlier, based upon RECIST 1.1 by the investigator review. Subjects without documented PD/death will be censored at the last disease assessment date.
    L'endpoint primario di sicurezza nelle parti 1, 2, 3, 4 e 5 dello studio è DLT. Nella Parte 3, non vi sarà Tier 1 endpoint di sicurezza, così come endpoint Tier 2 e Tier 3 di sicurezza saranno valutati come descritto nel protocollo, sezione 8.2.5.4). La tossicità e i gradi evidenziati dai soggetti che hanno ricevuto il trattamento in studio, inclusi gli eventi avversi (EA), eventi avversi seri(SAE) e gli eventi di interesse clinico (ECI) saranno riassunti. Altre misure di sicurezza valutati in tutte le parti dello studio comprendono valutazioni di sicurezza di laboratorio, ECG, segni vitali e esami fisici.
    L'endpoint primario di efficacia nella parte 3 sarà la sopravvivenza libera da progressione (PFS), e definita come il tempo dalla randomizzazione nella parte 3 (o l'inizio del trattamento, nelle altre parti ) alla progressione della malattia (PD) o il decesso, a seconda di quale si verifica per primo, basato sui criteri del RECIST 1.1 dalla revisione da parte dello sperimentatore. Soggetti senza documentata PD / decesso saranno censiti all’ultima data di valutazione della malattia.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At each cycle, and as clinically deemed.
    Ad ogni ciclo e come clinicamente ritenuto.
    E.5.2Secondary end point(s)
    Secondary endpoints include objective response rate (ORR) per RECIST 1.1, response duration per RECIST 1.1, overall survival (time to death), and the evaluation of pharmacokinetic properties of MK-3475, dabrafenib, and/or trametinib, when used in combination.
    Objective Response Rate (ORR) is defined as the percentage of subjects who have achieved confirmed complete response (CR) or partial response (PR) according to RECIST 1.1 by the investigator review.
    Subjects with missing outcome on objective response will be considered non-responders.
    Response Duration: is defined as the time interval between the date of the first confirmed response (CR/PR) (the response prior to confirmation) and the date of first documented disease progression
    based upon RECIST 1.1 by the investigator review. Response duration will be only determined for confirmed responses.
    Overall survival (OS): is defined as the time from randomization (or the start of treatment when there is no randomization) to death due to any cause. Subjects without documented death at the time of analysis will be censored at the date last known to be alive.
    Gli endpoint secondari comprendono il tasso di risposta obiettiva (ORR) per RECIST 1.1, durata della risposta per RECIST 1.1, la sopravvivenza globale (tempo fino a decesso), e la valutazione delle proprietà farmacocinetiche di MK-3475, Dabrafenib, e / o trametinib, se usati in combinazione. Il tasso di risposta obiettiva (ORR) è definito come la percentuale di soggetti che hanno raggiunto la risposta completa confermata (CR) o la risposta parziale (PR) secondo i criteri del RECIST 1.1 sulla base della revisione da parte dello sperimentatore. I soggetti con esito mancante della risposta obiettiva saranno considerati non-responder. Durata della risposta definita come l'intervallo di tempo tra la data della prima risposta confermata (CR / PR) (la risposta precedente la conferma), e la data della prima progressione documentata di malattia sulla base dei criteri del RECIST 1.1 sulla base della revisione da parte dello sperimentatore. La durata della risposta sarà determinata solo dalle risposte confermate.
    La sopravvivenza globale (OS): è definita come il tempo dalla randomizzazione (o l'inizio del trattamento, quando non c'è randomizzazione) al decesso per qualsiasi causa. Soggetti senza decesso documentato al momento dell'analisi saranno censiti all’ultima data in cui si è a conoscenza del soggetto in vita.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At each cycle, and as clinically deemed.
    Ad ogni ciclo e come clinicamente ritenuto.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Parts 1,2,4,5 of the study are Phase I dose confirmation of combination treatment
    Conferma dose trattamento combinato per parti 1,2, 4 e 5 Fase I
    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 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
    Parti 1 e 2 sono non-rand, in aperto (non EU); parte 3 doppio cieco; parti 4 e 5 (tutti) non rand, i
    Part 1,2(non-EU) 4,5 (all)non-randomized,open-label;Part3-double-blind
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    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
    Canada
    Israel
    New Zealand
    United States
    Denmark
    Italy
    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 years0
    E.8.9.1In the Member State concerned months48
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months48
    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: 134
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 56
    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 state57
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 190
    F.4.2.2In the whole clinical trial 219
    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)
    Once the subject has achieved the study objective or the study has ended, the subject is discontinued from this study and may be enrolled in an extension study to continue protocol-defined assessments and treatment.
    Una volta che il soggetto ha raggiunto l’obiettivo dello studio o lo studio è terminato, il soggetto interrompe lo studio e può essere arruolato in uno studio di estensione per proseguire con il trattamento e le valutazioni definite dal protocollo.
    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 Decision2015-11-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-07-22
    P. End of Trial
    P.End of Trial StatusCompleted
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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