Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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


    The EU Clinical Trials Register currently displays   40665   clinical trials with a EudraCT protocol, of which   6637   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2015-001327-23
    Sponsor's Protocol Code Number:ITP0815
    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:2015-04-29
    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 number2015-001327-23
    A.3Full title of the trial
    Eltrombopag as Second line Therapy in adult patients with primary Immune Thrombocytopenia (ESTIT study) in an attempt to achieve long-term remission: a single arm multicenter phase II clinical and biological study
    Eltrombopag come terapia di seconda linea in pazienti adulti con piastrinopenia immune primitiva (studio ESTIT) al fine di raggiungere la risposta a lungo termine: studio biologico e clinico di fase II multicentrico a singolo braccio
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study about the effect of a drug (Eltrombopag)which is administered in patients with thrombocytopenia primary Immune, a relative decrease of platelets in blood (small blood components that help the clotting process by sticking to the lining of blood vessels).
    Terapia con un farmaco denominato Eltrombopag successiva a quella di prima scelta per pazienti adulti con piastrinopenia, ovvero una diminuzione delle piastrine (piccole cellule circolanti nel sangue, che partecipano all'emostasi, cioè all'insieme di eventi che determinano l'arresto del sanguinamento quando un vaso viene leso) : studio biologico e clinico per valutare la sicurezza e l’efficacia che coinvolge più centri con un unico schema di trattamento per tutti i pazienti partecipanti.
    A.4.1Sponsor's protocol code numberITP0815
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02402998
    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 SponsorFondazione G.I.M.EM.A. Gruppo Italiano Malattie Ematologiche dell'Adulto
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGlaxoSmithKline S.P.A.
    B.4.2CountryItaly
    B.4.1Name of organisation providing supportA.I.L. Associazione Italiana contro le Leucemie
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationFondazione G.I.M.EM.A.
    B.5.2Functional name of contact pointCentro Dati GIMEMA
    B.5.3 Address:
    B.5.3.1Street Addressvia Casilina,5
    B.5.3.2Town/ cityRoma
    B.5.3.3Post code00182
    B.5.3.4CountryItaly
    B.5.4Telephone number+390670390526
    B.5.5Fax number+390670390540
    B.5.6E-mailgimema@gimema.it
    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 Yes
    D.2.1.1.1Trade name Revolade
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxoSmithKline Trading Services Limited
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/07/467
    D.3 Description of the IMP
    D.3.1Product nameRevolade
    D.3.4Pharmaceutical form 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 INNNA
    D.3.9.1CAS number 496775-62-3
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameELTROMBOPAG OLAMINE
    D.3.9.4EV Substance CodeSUB30141
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Revolade
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxoSmithKline Trading Services Limited
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/07/467
    D.3 Description of the IMP
    D.3.1Product nameRevolade
    D.3.4Pharmaceutical form 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 INNNA
    D.3.9.1CAS number 496775-62-3
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameELTROMBOPAG OLAMINE
    D.3.9.4EV Substance CodeSUB30141
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary Immune Thrombocytopenia
    Trombocitopenia immune primitiva
    E.1.1.1Medical condition in easily understood language
    Relative decrease of platelets in blood (small blood components that help the clotting process by sticking to the lining of blood vessels).
    Diminuzione delle piastrine (piccole cellule circolanti nel sangue, che partecipano all'emostasi, cioè all'insieme di eventi che determinano l'arresto del sanguinamento quando un vaso viene leso)
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10043554
    E.1.2Term Thrombocytopenia
    E.1.2System Organ Class 10005329 - Blood and lymphatic system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to investigate the long-term effect of Eltrombopag as a second line treatment in adult patients with primary ITP not responsive or in relapse after a full first line steroids treatment (prednisone or dexamethasone) ± IVIG (intravenous immunoglobulin).

    Valutare l’effetto a lungo termine di Eltrombopag come trattamento di seconda linea in pazienti adulti con ITP primitiva non responsiva o recidivata dopo un trattamento di prima linea completo con steroidi (prednisone o desametasone) ± IVIG (immunoglobuline intravenose).
    E.2.2Secondary objectives of the trial
    1.Evaluation of the duration of response (R) and complete response (CR) after Eltrombopag discontinuation;
    2. Evaluation of bleeding events;
    3. Evaluation of the modification of some immunological parameters during and after the treatment and their relationship with clinical outcome;
    4. Relationship between baseline TPO serum level and response to therapy.
    1. Valutazione della durata della risposta (R) e della risposta completa (CR) dopo l’interruzione di Eltrombopag;
    2. Valutazione degli eventi di sanguinamento;
    3. Valutazione della modifica di alcuni paramenti immunologici durante e dopo il trattamento e loro relazione con gli outcome clinici;
    4. Relazione tra i livelli di TPO sierico al basale e risposta alla terapia.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Diagnosis of primary ITP;
    2. Age ≥ 18 years;
    3. Patients are in the new diagnosis or persistent phase of disease (i.e. within month 12 from diagnosis);
    4. Patients not responsive or in relapse after a full course of steroid therapy (prednisone 1 mg/kg/d for at least 28 days or 3 cycles of dexamethasone 40 mg/day for consecutive 4 days, according to the GIMEMA ITP0207 trial) ± IVIG;
    5. Patients have a platelet count < 10 x 109/L documented in a single blood cell count;
    OR
    Patients have bleeding symptoms and a platelet count > 10 < 30 x 109/L documented in a single blood cell count; OR
    Patients have no bleeding symptoms and a platelet count >10 < 30 x 109/L in at least 2 blood cell counts at 3 days interval in the week preceding the enrolment with the last count at the day of enrolment;
    OR
    Patients have corticosteroids or IVIG dependence (the need for ongoing or repeated doses administration of corticosteroids or IVIG to maintain a platelet count ≥ 30 x 109/L and/or to avoid bleeding;
    6. Written informed consent obtained from the subject;
    7. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of enrolment randomization until 6 months after the last dose of study treatment;
    8. Female subjects of non-childbearing potential may be enrolled in the study; for this study population, non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause;
    OR
    Female subjects of childbearing potential may be enrolled in the study, if the subject has practiced adequate contraception for 30 days prior to start of Eltrombopag, has a negative pregnancy test within 14 days of first dose of Eltrombopag, and has agreed to continue adequate contraception during the entire treatment period and for 6 months after completion of the treatment.;
    Diagnosi di ITP primitiva;
    2. Età ≥ 18 anni;
    3. Pazienti di nuova diagnosi o nella fase persistente della patologia (entro il dodicesimo mese dalla diagnosi);
    4. Pazienti non responsivi o recidivati dopo un ciclo di terapia completo con steroidi (prednisone 1 mg/kg/die per almeno 28 giorni o 3 cicli di Desametasone 40 mg/die per 4 giorni consecutivi, in accordo allo studio ITP0207) ± IVIG;
    5. Pazienti con conta piastrinica < 10 x 109/L documentata con un singolo emocromo;
    6. Pazienti che mostrano sintomi di sanguinamento e una conta piastrinica > 10 < 30 x 109/L documentata in un singolo emocromo;
    7. Pazienti che non mostrino sintomi di sanguinamento e una conta piastrinica >10 < 30 x 109/L in almeno 2 conte delle cellule sanguigne in un intervallo di 3 giorni nella settimana precedente l’arruolamento e con l’ultima conta il giorno dell’arruolamento;
    8. Pazienti che necessitino di corticosteroidi o IVIG (necessità di somministrazione continua o ripetuta di corticosteroidi o IVIG per mantenere la conta piastrinica ≥ 30 x 109/L e/o evitare sanguinamento;
    9. Consenso informato scritto ottenuto dal soggetto;
    10. Uomini con una partner potenzialmente fertile devono aver effettuato una precedente vasectomia o devono dare il consenso ad utilizzare un metodo efficace di contraccezione dal momento dell’arruolamento fino a 6 mesi dopo l’ultima dose di trattamento in studio;
    11. Donne potenzialmente non fertili possono essere arruolate nello studio; per questa popolazione in studio, la potenziale non fertilità è definita come sterilizzazione tubarica, isterectomia, ovariectomia o post-menopausa; Oppure
    12. Donne potenzialmente fertili possono essere arruolate nello studio, se il soggetto ha praticato un’adeguata contraccezione per i 30 giorni precedenti all’inizio del trattamento con Eltrombopag, se ha un test di gravidanza negativo entro 14 giorni dalla prima dose di Eltrombopag e ha acconsentito all’utilizzo di un adeguato sistema di contraccezione durante l’intero periodo di trattamento e per 6 mesi dopo il completamento del trattamento.
    E.4Principal exclusion criteria
    1. Diagnosis of secondary ITP. As far as patients with immune thrombocytopenia and antiphospholipid antibodies positivity, individuals without a previous thromboembolic event are excluded only if lupus anticoagulant (LAC) is associated with the presence of anticardiolipin (aCL) and aβ2-Glycoprotein I (aβ2GPI) antibodies (triple positivity according to Pengo et al. Blood 2011) (10);
    2. Previous treatment with other anti-ITP second line therapies (i.e. Rituximab, Azathioprine, Cyclosporin-A or other); only patients with a previous full course of steroid (see inclusion criteria for definition) ± IVIG are admitted to the study;
    3. Previous treatment with any TPO-R agonists;
    4. Patients have life threatening bleeding complications;
    5. Patients had deep venous thrombosis (DVT) or arterial thrombosis in the 3 months preceding the enrolment;
    6. Patients are HIV, HCV, HBsAg positive;
    7. Patients with hepatic impairment (i.e. mild, moderate or severe hepatic impairment (Child-Pugh score > 6);
    8. Patients have a well established liver disease that represents a contraindication for the use of Eltrombopag;
    9. Patients are unable to respect the 4-hour interval between Eltrombopag and other medications (e.g. antacids), calcium-rich foods (e.g. dairy products and calcium fortified juices), or supplements containing polyvalent cations such as iron, calcium, aluminium, magnesium, selenium, and zinc;
    10. Patients are unable to stop medications that are known to cause a drug-drug interaction with Eltrombopag;
    11. Subjects meeting any of the following criteria must not be enrolled in an Eltrombopag study:
    a) Lactating female.
    b) History of another malignancy. Exception: subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
    c) Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance with the study procedures.
    d) Hormone replacement therapy. Subjects must discontinue hormone replacement therapy prior to study enrolment due to the potential for inhibition of Cytochrome P450 (CYP) enzymes that metabolize estrogens and progestins.
    e) Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
    f) Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Eltrombopag or excipients that contraindicate their participation.
    1. Diagnosi di ITP secondaria. I pazienti con piastrinopenia immune e positività ad anticorpi antifosfolipidici, senza eventi tromboembolici pregressi sono esclusi solo se l’anticoagulante lupico è associato alla presenza di anticorpi anticardiolipina (aCL) e aβ2-Glicoproteina I (aβ2GPI) (tripla positività secondo Pengo et al. Blood 2011);
    2. Trattamento pregresso con altre terapie anti-ITP di seconda linea (Rituximab, Azatioprina, Ciclosporina A o altri); i soli pazienti con un ciclo precedente completo di steroidi (vedi criteri di inclusione per la definizione) ± IVIG sono ammessi nello studio;
    3. Trattamento pregresso con qualsiasi agonista TPO-R;
    4. Pazienti che abbiano complicanze dovute a sanguinamento che mettano in pericolo la loro vita;
    5. Pazienti che abbiano trombosi venosa profonda o trombosi arteriosa nei 3 mesi precedenti l’arruolamento;
    6. Pazienti HIV, HCV, HBsAg positivi;
    7. Pazienti con insufficienza epatica (insufficienza epatica lieve, moderata o grave (Child-Pugh score > 6);
    8. Pazienti con patologie epatiche accertate in cui sia controindicato l’utilizzo di Eltrombopag;
    9. Pazienti che siano impossibilitati a rispettare l’intervallo di 4 ore tra Eltrombopag e altri trattamenti (come gli antiacidi), cibi ricchi di calcio (come prodotti giornalieri e succhi arricchiti di calcio), o altri integratori contenenti cationi polivalenti come ferro, calcio, alluminio, magnesio, selenio e zinco;
    10. Pazienti incapaci di interrompere i trattamenti per i quali sia noto l’effetto di interazione farmaco-farmaco con Eltrombopag;
    11. Soggetti che presentino uno qualsiasi dei seguenti criteri non devono essere arruolati in uno studio con Eltrombopag:
    a) Donne in allattamento.
    b) Storia di altra malignità. Eccezione: soggetti che hanno mostrato assenza di malattia per 5 anni, o soggetti con storia di carcinoma della pelle non-melanoma asportato completamente o con carcinoma in situ trattato con successo sono eleggibili.
    c) Qualsiasi patologia medica o psichiatrica pre-esistente, grave e/o instabile o altre condizioni che possono interferire con la sicurezza del soggetto, con l’ottenimento del consenso informato o con la compliance con le procedure dello studio.
    d) Terapia ormonale sostitutiva. I soggetti devono interrompere la terapia ormonale sostitutiva prima dell’arruolamento in studio a causa della potenziale inibizione degli enzimi del citocromo P450 (CYP) che metabolizzano gli estrogeni e i progestinici.
    e) Somministrazione di un farmaco sperimentale entro 30 giorni o 5 emivite, qualunque sia la più lunga, che preceda la prima dose del trattamento in studio.
    f) Nota reazione di ipersensibilità immediata o ritardata o idiosincrasia ai farmaci chimicamente correlati a Eltrombopag o eccipienti per i quali sia controindicato l’utilizzo nello studio.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of subjects who achieve long-term response (6 months sustained response) and able to taper down the dose. A patient will achieve this endpoint if at the end of the period of treatment he/she reaches to discontinue Eltrombopag and if, after discontinuation, has absence of bleeding and maintains a platelet count ≥ 30 x 109/L and at least a 2-fold increase from the baseline count in blood cell count performed in the 6 months of the period observation, during which no steroid, Eltrombopag, other anti TPO-R agonists and other anti-ITP medications are administered.
    Percentuale di soggetti che raggiungono la risposta a lungo termine (6 mesi di risposta sostenuta ) e in grado di ridurre gradualmente la dose. Un paziente raggiungerà questo endpoint se alla fine del periodo di trattamento interrompe Eltrombopag e se , dopo la sospensione, ha assenza di sanguinamento e mantiene la conta piastrinica ≥ 30 x 109 / L e aumenta almeno di 2 volte la conta al baseline delle cellule del sangue effettuata nei 6 mesi del periodo di osservazione, durante il quale non vengono somministrati steroidi, eltrombopag, altri agonisti TPO - R e altri farmaci anti- anti- ITP.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At the end of the study
    Al termine dello studio
    E.5.2Secondary end point(s)
    1. Duration of R and CR: duration of R and CR from Eltrombopag discontinuation to the last follow up according to the IWG criteria (11);
    2. Bleeding events: bleeding will be evaluated according to the SMOG bleeding scale (Appendix B).
    3. Modification of immunological parameters during treatment and their relationship with clinical outcome. This study will be performed and completed in all patients enrolled into the study (responders and no-responders). The following biological markers will be evaluated from peripheral blood at baseline, week 24, 36 and 52:
    a) Cytokine serum levels (IL-1, IL-8, TNFa, IL-6, IL-4, IL-10, IL-17, IL-22, IFNγ, osteopontin);
    b) Lymphocyte subpopulations: B (CD19+), marginal zone B (CD19+ CD27+ IgD+), switching memory B (CD19+ CD27+ IgD+), T (CD3+), T helper (CD4+) T cytotoxic (CD8+), Th effector memory (CD4+CD45R0+CCR7-), Th central memory (CD4+ CD45R0+ CCR7+) and Th naïve (CD4+ CD45RA+), T cytotoxic memory and naïve (CD45RA+/R0+), effector T cytotoxic (CD8+ perforin+), regulatory T cells (CD4+ CD25+Foxp3+), Tgamma/delta (TCRγδ+), NK (CD16+ CD56+), NKT (TCRαv24+ β11+), myeloid dendritic cells (HLA-DR+ CD11c+), plasmacytoid dendritic cells (Lin-HLA-DR+ CD123+).
    c) Cytokine production by T cells ex vivo (ELISA and intracytoplasmic staining): IL-4 (TH2 cells), IFNγ (TH1), IL-17 (TH17), IL-10 (Treg), IL-9 (TH9), IL-22 (TH22)
    d) Cytokine production by myeloid dendritic cells (intracytoplasmic staining): IL-10, IL-12.
    4. Relationship between baseline TPO serum level and response to therapy: TPO will be measured using a Human TPO duo-set assay (R&D System). This assay employs the quantitative sandwich enzyme immunoassay technique to evaluate the concentration of TPO in plasma or serum
    1. Durata di R e CR: durata R e CR dalla sospensione di Eltrombopag all'ultimo follow-up secondo i criteri IWG (11);
    2. Gli eventi di sanguinamento: il sanguinamento sarà valutata in base alla scala di sanguinamento SMOG;
    3. Modifica dei parametri immunologici durante il trattamento e la loro relazione con l'outcome clinico. Questo studio sarà eseguito e completato in tutti i pazienti arruolati nello studio (responders e non-responders). I seguenti marcatori biologici saranno valutati su sangue periferico al basale, settimana 24, 36 e 52:
    a) i livelli sierici di citochine (IL-1, IL-8, TNFa, IL-6, IL-4, IL-10, IL-17, IL-22, IFNγ, osteopontina);
    e) b) sottopopolazioni linfocitarie: B (CD19+), marginal zone B (CD19+ CD27+ IgD+), switching memory B (CD19+ CD27+ IgD+), T (CD3+), T helper (CD4+) T cytotoxic (CD8+), Th effector memory (CD4+CD45R0+CCR7-), Th central memory (CD4+ CD45R0+ CCR7+) and Th naïve (CD4+ CD45RA+), T cytotoxic memory and naïve (CD45RA+/R0+), effector T cytotoxic (CD8+ perforin+), regulatory T cells (CD4+ CD25+Foxp3+), Tgamma/delta (TCRγδ+), NK (CD16+ CD56+), NKT (TCRαv24+ β11+), myeloid dendritic cells (HLA-DR+ CD11c+), plasmacytoid dendritic cells (Lin-HLA-DR+ CD123+).

    c) la produzione di citochine da parte delle cellule T ex vivo (ELISA e colorazione intracitoplasmatica): IL-4 (le cellule TH2), IFNγ (TH1), IL-17 (TH17), IL-10 (Treg), IL-9 (TH9), IL-22 (Th22)
    d) la produzione di citochine da parte delle cellule dendritiche mieloidi (colorazione intracitoplasmatica): IL-10, IL-12.
    4. Relazione tra livelli sierici basali TPO e la risposta alla terapia: TPO sarà misurata con un test TPO umano duo-set (R & S System). Questo test utilizza la tecnica enzimatica quantitativa a sandwich immunoassay per valutare la concentrazione di TPO nel plasma o nel siero
    E.5.2.1Timepoint(s) of evaluation of this end point
    At the end of the study
    Al termine dello studio
    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 No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned12
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial 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: 32
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 state52
    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)
    The patients will continue to be treated according to current clinical practice
    I pazienti continueranno ad essere trattati secondo normale pratica clinica
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation G. I. M. EM. A. Gruppo Italiano Malattie Ematologico dell’Adulto
    G.4.3.4Network Country Italy
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-06-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-06-23
    P. End of Trial
    P.End of Trial StatusCompleted
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA