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    Summary
    EudraCT Number:2020-003809-60
    Sponsor's Protocol Code Number:XPORT-MF-035
    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:2021-07-27
    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 number2020-003809-60
    A.3Full title of the trial
    A phase 2, randomized, open-label, multicenter study to evaluate safety and efficacy of single agent selinexor versus treatment of physician's choice in patients with previously treated myelofibrosis
    Studio multicentrico di fase 2, randomizzato, in aperto, per valutare la sicurezza e l’efficacia di selinexor come singolo agente rispetto al trattamento scelto dal medico in pazienti con mielofibrosi precedentemente trattata
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Studio per valutare la sicurezza e l'efficacia del selinexor vs. trattamento di scelta del medico in pazienti con mielofibrosi già precedentemente trattata.
    A Study to Evaluate Safety and Efficacy of Selinexor Versus Treatment of Physician's Choice in Participants With Previously Treated Myelofibrosis
    A.3.2Name or abbreviated title of the trial where available
    XPORT-MF-035
    XPORT-MF-035
    A.4.1Sponsor's protocol code numberXPORT-MF-035
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04562870
    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 SponsorKARYOPHARM THERAPEUTICS, 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 supportKaryopharm Therapeutics Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKaryopharm Therapeutics Inc.
    B.5.2Functional name of contact pointClinical Trial Information Desk.
    B.5.3 Address:
    B.5.3.1Street Address85 Wells Avenue
    B.5.3.2Town/ cityNewton
    B.5.3.3Post codeMA 02459
    B.5.3.4CountryUnited States
    B.5.4Telephone number000000000000
    B.5.5Fax number000000000000
    B.5.6E-mailclinicaltrials@karyopharm.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 Yes
    D.2.1.1.1Trade name Ondansetron tablet, Aurobindo Pharma Limited
    D.2.1.1.2Name of the Marketing Authorisation holderAurobindo Pharma Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameOndans etron
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Dispersible 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 INNONDANSETRON
    D.3.9.2Current sponsor codeOndansetron
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number8
    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: 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 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 nameSelinexor
    D.3.2Product code [KPT-330]
    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 INNSelinexor
    D.3.9.1CAS number 1393477-72-9
    D.3.9.2Current sponsor codeKPT-330
    D.3.9.4EV Substance CodeSUB177942
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Myelofibrosis
    Mielofibrosi
    E.1.1.1Medical condition in easily understood language
    Myelofibrosis
    Mielofibrosi
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10028537
    E.1.2Term Myelofibrosis
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10077161
    E.1.2Term Primary myelofibrosis
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10074689
    E.1.2Term Post polycythemia vera myelofibrosis
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10074691
    E.1.2Term Post polycythaemia vera myelofibrosis
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10074690
    E.1.2Term Post essential thrombocythemia myelofibrosis
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the clinical activity of selinexor monotherapy compared with physician's choice (PC) in patients with previously treated myelofibrosis (MF).
    Determinare l’attività clinica di selinexor in monoterapia rispetto alla PC in pazienti con MF precedentemente trattata
    E.2.2Secondary objectives of the trial
    Key Secondary
    • To evaluate additional measures of clinical activity of selinexor compared to physician's choice (PC) in patients with myelofibrosis (MF).
    Other Secondary
    • To assess the survival outcome of patients with myelofibrosis (MF) receiving selinexor compared with physician's choice (PC).
    • To evaluate additional measures of clinical activity of selinexor compared to physician's choice (PC) in patients with myelofibrosis (MF).
    • To determine the safety profile of selinexor and compare to physician's choice (PC) in patients with myelofibrosis (MF).
    • To characterize pharmacokinetics (PK) of selinexor in patients with myelofibrosis (MF).
    Exploratory:
    • To evaluate patient reported outcomes in patients with MF receiving selinexor compared to PC.
    • To identify predictive biomarkers of response to treatment and explore treatment mechanism of action in patients with MF.
    • Assess changes in transfusion requirements
    • Assess changes in serum LDH levels
    Secondario principale
    • Valutare misure aggiuntive dell’attività clinica di selinexor rispetto alla PC in pazienti con MF.
    Altri secondari
    • Valutare l’esito in termini di sopravvivenza dei pazienti con MF trattati con selinexor rispetto a quelli trattati con la PC.
    • Valutare misure aggiuntive dell’attività clinica di selinexor rispetto alla PC in pazienti con MF.
    • Determinare il profilo di sicurezza di selinexor e confrontarlo con quello della PC in pazienti affetti da MF.
    • Caratterizzare la farmacocinetica (PK) di selinexor in pazienti affetti da MF.
    Esplorativi
    • Valutare gli esiti riferiti dal paziente nei pazienti affetti da MF trattati con selinexor rispetto a quelli trattati con la PC.
    • Identificare biomarcatori predittivi di risposta al trattamento ed esplorare il meccanismo d’azione del trattamento in pazienti con MF.
    • Valutare le variazioni nel fabbisogno trasfusionale
    • Valutare le variazioni nei livelli sierici di LDH
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients are eligible to be included in the study only if they meet all of the following criteria:
    Main Inclusion Criteria
    1. A diagnosis of primary MF or post-ET or post-PV MF according to the 2016 WHO classification of MPN (Protocol Appendix 2), confirmed by the most recent local pathology report.
    2. Previous treatment with JAK inhibitors for at least 6 months.
    3. Measurable splenomegaly during the screening period as demonstrated by spleen volume of =450 cm3 by MRI or CT scan
    4. Relapsed, refractory or intolerant to JAK inhibitors as defined as meeting one of the criteria below:
    a. <35% spleen volume reduction by MRI or CT-scan (from baseline) or
    b. <50% decrease in spleen size by palpation (from baseline) or an increase of at least 3 cm with the spleen at least 5 cm below the left
    costal margin or
    c. Spleen volume increase >25% from nadir or a return to within 10% of baseline after any initial response or
    d. Treatment with JAK inhibitor was complicated by development of RBC transfusion requirement (2 units per month for 2 month); or grade 3
    thrombocytopenia, anemia, hematoma/hemorrhage; or Grade 2 nonhematologic toxicity while on JAK inhibitors
    5. Patients =18 years of age
    6. ECOG =2
    7. Platelet count =100 × 109/L
    8. Absolute neutrophil count (ANC) =1.5 × 109/L
    9. Serum direct bilirubin =1.5 × ULN; AST and ALT = 2.5 × ULN
    10. Calculated creatinine clearance (CrCl) >15 mL/min based on the
    Cockcroft and Gault formula.
    11. Patients with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is
    <100 IU/mL.
    12. Patients with untreated hepatitis C virus (HCV) are eligible if there is a documentation of negative viral load per institutional standard.
    13. Patients with history of human immunodeficiency virus (HIV) are eligible if they have CD4+ T-cell counts =350 cells/µL, negative viral
    load per institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
    14. Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective
    methods of contraception throughout the study and for one month following the last dose of study treatment. Childbearing potential excludes: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy.
    15. Male patients who are sexually active must use highly effective methods of contraception throughout the study and for one month following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period.
    16. Patients must sign written informed consent in accordance with federal, local and institutional guidelines.
    Il crossover dal braccio scelto dal medico (PC) al braccio selinexor (S) sarà consentito per i pazienti che sviluppano malattia progressiva (aumento> 25%) o per quelli con riduzione <35% alla settimana 36. I pazienti devono soddisfare tutti i criteri di inclusione ed esclusione prima del crossover. I pazienti che hanno superato il crossover a causa di PD (aumento> 25%) confermato da IRC o per riduzione <35% delle dimensioni della milza alla settimana 36, dovrebbero avere un wash-out di 10 giorni dall'ultima dose nel braccio PC.
    1. Diagnosi di MF primaria o MF post-trombocitemia essenziale (ET) o post-policitemia vera (PV) secondo la classificazione OMS 2016 delle MPN (Appendice 2), confermata dal più recente referto patologico locale.
    2. Precedente trattamento con inibitori di JAK per almeno 6 mesi.
    3. Splenomegalia misurabile durante il periodo di screening, come dimostrato dal volume splenico
    =450 cm3 mediante risonanza(MRI )o tomografia computerizzata (CT-scan)
    4. Il soggetto è recidivante, refrattario o intollerante agli inibitori di JAK, in base al soddisfacimento di uno dei seguenti criteri:
    a. riduzione (rispetto al basale) del volume splenico <35% mediante MRI o CT-scan, oppure
    b. riduzione (rispetto al basale) delle dimensioni della milza <50% mediante palpazione o aumento di almeno 3 cm con la milza ad almeno 5 cm sotto il margine costale sinistro, oppure
    c. aumento del volume della milza >25% rispetto al nadir o ritorno a entro il 10% del valore
    basale dopo qualsiasi risposta iniziale, oppure
    d. trattamento con un inibitore di JAK complicato dall’insorgenza della necessità di trasfusioni di globuli rossi -RBC- (2 unità al mese per 2 mesi); o trombocitopenia di grado 3, anemia, ematoma/emorragia; o tossicità non ematologica di grado 2 durante il trattamento con inibitori di JAK.
    5. Pazienti di età =18 anni
    6. Stato di validità secondo il Gruppo cooperativo orientale di oncologia (ECOG) =2
    7. Conta piastrinica =100 × 109/l
    8. Conta assoluta dei neutrofili (ANC) =1,5 × 109/l
    9. Bilirubina diretta sierica =1,5 × limite superiore alla norma (ULN); aspartato aminotransferasi (AST) e alanina aminotransferasi (ALT) =2,5 × ULN
    10. Clearance della creatinina calcolata (CrCl) >15 ml/min in base alla formula di Cockcroft e Gault.
    11. i pazienti con infezione attiva da virus dell’epatite B (HBV) sono idonei se la terapia antivirale per l’epatite B è stata somministrata per >8 settimane e la carica virale è <100 UI/ml.
    12. I pazienti con infezione da virus dell’epatite C (HCV) non trattata sono idonei in caso di documentata negatività della carica virale secondo lo standard istituzionale.
    13. I pazienti con anamnesi di infezione da virus dell’immunodeficienza umana (HIV) sono idonei se presentano conte delle cellule T CD4+ =350 cellule/µl, carica virale negativa secondo lo standard istituzionale e nessuna anamnesi di infezioni opportunistiche indicative di sindrome da immunodeficienza acquisita (AIDS) nel corso dell’ultimo anno.
    14. I pazienti di sesso femminile in età fertile devono presentare un test di gravidanza sul siero negativo allo screening e accettare di utilizzare metodi contraccettivi altamente efficaci per tutta la durata dello studio e per un mese dopo l’ultima dose del trattamento dello studio. L’età fertile esclude: età >50 anni e amenorrea per cause naturali per >1 anno, oppure pregressa salpingo- ovariectomia bilaterale o isterectomia.
    15. I pazienti di sesso maschile sessualmente attivi devono utilizzare metodi contraccettivi altamente efficaci per tutta la durata dello studio e per un mese dopo l’ultima dose di trattamento dello studio. I pazienti di sesso maschile devono acconsentire a non donare sperma durante il periodo di trattamento dello studio.
    16. I pazienti devono firmare il consenso informato scritto in conformità alle linee guida federali, locali e istituzionali.
    Crossover from physician's choice (PC) arm to selinexor (S) arm will be allowed for patients who develop progressive disease (>25% increase) or for those with <35% reduction at the Week 36. Patients should meet all inclusion and exclusion criteria prior to crossover. Patients who crossover due to PD (>25% increase) onfirmed by IRC or due to <35% reduction in spleen size at Week 36, should have a wash-out of 10 days from last dose in Arm PC.
    E.4Principal exclusion criteria
    Patients are excluded from the study if any of the following criteria apply:
    1. >5% blasts in peripheral blood or >10% blasts in bone marrow (i.e., accelerated phase).
    2. Previous treatment with selinexor or other XPO1 inhibitors.
    3. Use of any standard or experimental anti-MF therapy <21 days prior to Cycle 1 Day 1 (hydroxyurea is allowed).
    4. Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (Example: vomiting, or
    diarrhea that is CTCAE grade >1).
    5. Received strong cytochrome P450 3A (CYP3A) inhibitors =7 days prior o selinexor dosing OR strong CYP3A inducers =14 days prior to
    selinexor dosing (Protocol Appendix 3).
    6. Major surgery <28 days prior to C1D1.
    7. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
    8. Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, prevent the patient from giving informed consent, or being compliant with the study procedures.
    9. Female patients who are pregnant or lactating.
    1. Percentuale di blasti nel sangue periferico >5% o percentuale di blasti midollo osseo >10%
    (ovvero, fase accelerata).
    2. Precedente trattamento con selinexor o altri inibitori di XPO1.
    3. Uso di qualsiasi terapia anti-MF standard o sperimentale <21 giorni prima del Ciclo 1 Giorno 1 (è consentito l’uso di idrossiurea).
    4. Compromissione della funzione gastrointestinale (GI) o malattia GI che potrebbe alterare significativamente l’assorbimento di selinexor (esempio: vomito o diarrea di grado >1 secondo i Criteri di terminologia comuni per gli eventi avversi [CTCAE]).
    5. Pazienti che hanno ricevuto forti inibitori del citocromo P450 3A (CYP3A) =7 giorni prima della somministrazione di selinexor OPPURE forti induttori del CYP3A =14 giorni prima della somministrazione di selinexor (Appendice 3).
    6. Intervento di chirurgia maggiore <28 giorni prima del C1G1.
    7. Infezione non controllata (ovvero, clinicamente instabile) con necessità di antibiotici, antivirali o antifungini per via parenterale entro 7 giorni prima della prima dose di trattamento dello studio; tuttavia, l’uso profilattico di questi agenti è considerato accettabile (anche per via parenterale).
    8. Qualsiasi malattia, condizione medica o disfunzione d’organo pericolosa per la vita che, a giudizio dello sperimentatore, potrebbe compromettere la sicurezza del paziente, impedire al paziente di fornire il consenso informato o la sua aderenza alle procedure dello studio.
    9. Pazienti di sesso femminile in stato di gravidanza o allattamento
    E.5 End points
    E.5.1Primary end point(s)
    Rate of Spleen Volume Reduction of =35% (SVR35) based on the response assessment by the Independent Radiology Committee (IRC)
    Tasso di riduzione del volume splenico =35% (SVR35) in base alla valutazione della risposta da parte del Comitato di radiologia indipendente (IRC).
    E.5.1.1Timepoint(s) of evaluation of this end point
    From Baseline up to Week 48
    Dalla Baseline alla Settimana 48
    E.5.2Secondary end point(s)
    Key Secondary
    • Rate of Total Symptom Score reduction of =50% (TSS50) in the myelofibrosis symptom assessment form (MFSAF) V4.0, based on local assessment
    • Rate of Spleen Volume Reduction of =25% (SVR25) based on the response assessment by the Independent Radiology Committee (IRC)
    Other Secondary
    • Overall survival (OS)
    • Anemia response as defined per the IWG-MRT (International Working Group – Myeloproliferative Neoplasms Research and Treatment) criteria, based on local assessment
    • Duration of SVR35 and SVR25, based on IRC assessment
    • Duration of TSS50, based on local assessment
    • ORR (Complete Response [CR] + Partial Response [PR] + Clinical Improvement [CI]) by IWG-MRT criteria, based on local assessment
    The occurrence, nature, and severity of AEs
    Population PK derived parameters:
    • AUC
    • Cmax
    Secondario principale
    • Tasso di riduzione del punteggio totale dei sintomi =50% (TSS50) nel modulo di valutazione dei sintomi della mielofibrosi (MFSAF) V4.0, in base alla valutazione locale
    • Tasso di riduzione del volume splenico =25% (SVR25) in base alla valutazione della risposta da parte dell’IRC
    Altri secondari
    • Sopravvivenza complessiva (OS)
    • Risposta dell’anemia, definita in base ai criteri IWG-MRT, secondo la valutazione locale
    • Durata della SVR35 e SVR25, in base alla valutazione dell’IRC
    • Durata del TSS50 in base alla valutazione locale
    • ORR (risposta completa [CR] + risposta parziale [PR] + miglioramento clinico [CI]) secondo i criteri IWG-MRT, in base alla valutazione locale
    • Incidenza, natura e gravità degli AE
    Parametri derivati dalla PK di popolazione:
    • Area sotto la curva (AUC)
    • Cmax
    E.5.2.1Timepoint(s) of evaluation of this end point
    Key Secondary Endpoints
    • From Baseline up to end of last cycle (approximately 48 months)
    • From Baseline up to Week 48
    Other Secondary Endpoints
    • From Baseline up to 12 months after end of treatment (approximately 60 months)
    • From Baseline up to 28 Days after last dose (approximately 48 months)
    • From Baseline up to 28 Days after last dose (approximately 48 months)
    • From Baseline up to 28 Days after last dose (approximately 48 months)
    • From Baseline up to 28 Days after last dose (approximately 48 months)
    From first dose of study treatment up to 30 days after end of treatment (approximately 48 months) ]
    PK parameter: Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days)
    Endpoints secondari principali
    • Dalla Baseline alla fine dell'ultimo cilco (circa 48 mesi)
    • Dalla Baseline alla Settimana 48
    Altri Endpoints secondari
    • Dalla Baseline fino a 12 mesi dopo la fine del trattamento (circa 60 mesi)
    • Dalla Baseline fino a 28 giorni dopo l'ultima dose (circa 48 mesi)
    • Dalla Baseline fino a 28 giorni dopo l'ultima dose (circa 48 mesi)
    • Dalla Baseline fino a 28 giorni dopo l'ultima dose (circa 48 mesi)
    • Dalla Baseline fino a 28 giorni dopo l'ultima dose (circa 48 mesi)
    Dalla prima dose del trattamento di studio fino a 30 giorni dopo la fine del trattamento (circa 48 mesi) ]
    Parametri PK: Ciclo 2 Giorno 1: 1, 2, 4, 6, e 24 ore dopo la dose (ogni ciclo è di 28 giorni)
    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) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over Yes
    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 Yes
    E.8.2.3.1Comparator description
    Scelta del medico per pratica clinica
    physician's choice as per clinical practice
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA24
    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
    United States
    Austria
    France
    Hungary
    Italy
    Poland
    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
    The end of study (Last Patient, Last Visit) (EoS) will occur upon completion of the Survival Follow-up period for the last patient treated who remains on treatment in the study. Completion of follow-up for the last patient will occur when this patient has been followed for up to 1 year after the End of Treatment (EoT) visit (discontinuation of treatment, patient has withdrawn consent, has been withdrawn from the study, has died, or has been lost to follow-up, whichever occurs first).
    La fine dello studio (Ultimo paziente, ultima visita) (EoS) avverrà al termine del periodo di FU di sopravvivenza per l'ultimo paziente trattato che rimane in trattamento. Il completamento del FU per l'ultimo paziente avverrà quando questo paziente è stato seguito fino a 1 anno dopo la visita di fine trattamento (EoT) (interruzione del trattamento, il paziente ha ritirato il consenso, è stato ritirato dallo studio, è morto o è stato perso per il FU, a seconda di quale si verifica per primo).
    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 months4
    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 months4
    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: 23
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 89
    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 state21
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 92
    F.4.2.2In the whole clinical trial 112
    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)
    After the end of treatment visit each randomized patient will enter in a Survival Follow-up period. The Survival Follow-up period will last until the last patient will complete it. Completion of follow-up for the last patient will occur when this patient has been followed for up to 1 year after the End of Treatment (EoT) visit (discontinuation of treatment, patient has withdrawn consent, has been withdrawn from the study, has died, or has been lost to follow-up, whichever occurs first).
    Dopo la fine del trattamento ogni paziente randomizzato entrerà in un periodo di FU di sopravvivenza. Il periodo di FU di sopravvivenza durerà fino a quando l'ultimo paziente non lo completerà. Il completamento del FU per l'ultimo paziente avverrà quando questo paziente è stato seguito fino a 1 anno dopo la visita EoT (interruzione del trattamento, il paziente ha ritirato il consenso, è stato ritirato dallo studio, è morto o è stato perso per il FU, a seconda di quale si verifica per primo).
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-08-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-30
    P. End of Trial
    P.End of Trial StatusOngoing
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