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    Summary
    EudraCT Number:2020-005234-15
    Sponsor's Protocol Code Number:BLU-285-3101
    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:2022-01-26
    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 number2020-005234-15
    A.3Full title of the trial
    A Phase 1/2, Single-arm Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of Avapritinib in Pediatric Patients with Solid Tumors Dependent on KIT or PDGFRA Signaling
    Studio di fase 1/2 single-arm, volto a valutare la sicurezza, la farmacocinetica e l’attività antitumorale di Avapritinib in pazienti pediatrici con tumori solidi dipendenti dalle vie di segnalazione di KIT o PDGFRA
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Avapritinib in Pediatric Patients with Solid Tumors Dependent on KIT or PDGFRA Signaling
    Studio di Avapritinib in pazienti pediatrici con tumori solidi dipendenti dalle vie di segnalazione di KIT o PDGFRA
    A.3.2Name or abbreviated title of the trial where available
    not applicable
    non applicabile
    A.4.1Sponsor's protocol code numberBLU-285-3101
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04773782
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/007/2020
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBLUEPRINT MEDICINES CORPORATION
    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 supportBlueprint Medicines Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBlueprint Medicines Corporation
    B.5.2Functional name of contact pointMedical Information
    B.5.3 Address:
    B.5.3.1Street Address45 Sidney Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number0016173747580
    B.5.5Fax number0000000000000
    B.5.6E-mailmedinfo@blueprintmedicines.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 nameAvapritinib
    D.3.2Product code [BLU-285]
    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 INNAVAPRITINIB
    D.3.9.2Current sponsor codeBLU-285
    D.3.9.4EV Substance CodeSUB192781
    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 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 nameAvapritinib
    D.3.2Product code [BLU-285]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Yes
    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 INNAVAPRITINIB
    D.3.9.2Current sponsor codeBLU-285
    D.3.9.4EV Substance CodeSUB192781
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 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 nameAvapritinib
    D.3.2Product code [BLU-285]
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation Yes
    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 INNAVAPRITINIB
    D.3.9.2Current sponsor codeBLU-285
    D.3.9.4EV Substance CodeSUB192781
    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.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
    Solid Tumors Dependent on KIT or PDGFRA Signaling
    Tumori solidi dipendenti dalle vie di segnalazione di KIT o PDGFRA
    E.1.1.1Medical condition in easily understood language
    Certain genetically defined pediatric solid tumors
    Alcuni tumori solidi pediatrici geneticamente definiti
    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 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
    Part 1
    - To determine the Part 2 recommended dose of avapritinib as a single agent in pediatric patients 2 to <18 years of age with advanced solid tumors, including CNS tumors, harboring mutations (including nonsynonymous point mutations, insertions, and deletions) in KIT or PDGFRA, or gliomas harboring the H3K27M mutation
    - To assess the safety and tolerability of avapritinib in pediatric patients.

    Part 2
    - To assess anti-tumor activity of avapritinib in pediatric patients by response evaluation criteria in solid tumors (RECIST v1.1 or Response Assessment in Neuro-Oncology [RANO]).
    Parte 1
    • Determinare la dose raccomandata della Parte 2 di avapritinib come agente singolo in pazienti pediatrici di età compresa tra 2 e <18 anni affetti da tumori solidi in stadio avanzato, inclusi tumori del SNC, portatori di mutazioni (tra cui mutazioni puntiformi non sinonime, inserzioni e delezioni) in KIT o PDGFRA, o gliomi che presentano la mutazione H3K27M.
    • Valutare la sicurezza e la tollerabilità di avapritinib in pazienti pediatrici.

    Parte 2
    • Valutare l’attività antitumorale di avapritinib in pazienti pediatrici in base ai criteri di valutazione della risposta nei tumori solidi (RECIST v1.1 o Valutazione della risposta in neuro-oncologia [RANO]).
    E.2.2Secondary objectives of the trial
    Part 1
    - To assess anti-tumor activity of avapritinib in pediatric patients by RECIST v1.1 or RANO.
    Part 1 and Part 2
    - To assess the safety and tolerability of avapritinib in pediatric patients (Part 2).
    - To assess the anti-tumor activity of avapritinib in pediatric patients by Response Assessment in Pediatric Neuro-Oncology (RAPNO) in patients with diffuse intrinsic pontine glioma (DIPG) and HGG, at institutions where assessment by RAPNO is performed.
    - To assess duration of response (DOR), progression-free survival, and disease control rate (DCR) of avapritinib in pediatric patients.
    - To characterize the pharmacokinetic (PK) profile of avapritinib and any clinically-relevant metabolites in pediatric patients.
    - To characterize pharmacodynamic markers.
    Obiettivi secondari
    Parte 1
    • Valutare l’attività antitumorale di avapritinib in pazienti pediatrici in base ai criteri RECIST v1.1 o RANO.
    Parte 1 e Parte 2
    • Valutare la sicurezza e la tollerabilità di avapritinib in pazienti pediatrici (Parte 2).
    • Valutare l’attività antitumorale di avapritinib in pazienti pediatrici mediante valutazione della risposta in neuro-oncologia pediatrica (RAPNO) in pazienti affetti da glioma pontino intrinseco diffuso (DIPG) e HGG, presso istituti in cui venga eseguita la valutazione RAPNO.
    • Valutare la durata della risposta (DOR), la sopravvivenza libera da progressione e il tasso di controllo della malattia (DCR) di avapritinib in pazienti pediatrici.
    • Caratterizzare il profilo farmacocinetico (PK) di avapritinib e di qualsiasi metabolita clinicamente rilevante in pazienti pediatrici.
    • Caratterizzare i marcatori farmacodinamici.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Patient is 2 to <18 years of age at the time the parent/guardian signs the Informed Consent Form.
    - Confirmed diagnosis of a R/R solid tumor with a mutation (including non-synonymous point mutations, insertions, and deletions) in KIT or PDGFRA that has progressed despite standard therapy and no alternative treatment options are available OR Confirmed diagnosis of H3K27M mutant glioma that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the Investigator.
    - Disease extent:
    -Part 1: All patients must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated.
    -Part 2: All patients must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For patients with H3K27M mutant glioma or KIT/PDGFRA mutant solid tumors, including CNS tumors, that have progressed despite prior therapy who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated. For patients with H3K27M mutant gliomas where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
    - Patients with CNS disease should be on a stable dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
    - Patients must have a Lansky (=16 years of age) or Karnofsky (>16 years of age) score of at least 50.
    • Il/La paziente ha un’età compresa tra 2 e <18 anni al momento della firma del modulo di consenso informato da parte del genitore/tutore.
    • Diagnosi confermata di un tumore solido R/R con una mutazione (comprese mutazioni puntiformi non sinonime, inserzioni e delezioni) nei geni KIT o PDGFRA che sia progredito nonostante la terapia standard e non siano disponibili opzioni terapeutiche alternative OPPURE Diagnosi confermata di glioma mutante H3K27M che non abbia risposto alla terapia standard o per il quale non esista alcuna terapia standard che possa fornire un beneficio clinico, secondo il giudizio dello sperimentatore.
    • Estensione della malattia:
    o Parte 1: tutti/e i/le pazienti devono presentare almeno 1 lesione misurabile secondo i criteri RECIST v1.1, RANO o RAPNO (per i tumori del SNC). Se è stata somministrata radioterapia, almeno 1 lesione misurabile non deve essere stata irradiata o deve essere chiaramente progredita dal momento dell’irradiazione.
    o Parte 2: tutti/e i/le pazienti devono presentare almeno 1 lesione misurabile secondo i criteri RECIST v1.1, RANO o RAPNO (per i tumori del SNC). Per i/le pazienti con glioma H3K27M mutante o tumori solidi KIT/PDGFRA mutanti, compresi i tumori del SNC, che abbiano mostrato progressione nonostante la precedente terapia e che abbiano ricevuto radioterapia, almeno 1 lesione misurabile non deve essere stata irradiata o deve avere manifestato una chiara progressione dal momento dell’irradiazione. Per i/le pazienti con gliomi H3K27M mutanti per cui non esista una terapia standard che possa trasmettere un beneficio clinico secondo il giudizio dello sperimentatore, non è necessaria la progressione della malattia di una lesione misurabile in seguito all’irradiazione.
    • I/Le pazienti con malattia del SNC devono assumere una dose stabile di corticosteroidi per almeno 7 giorni prima della prima dose di avapritinib, senza alcun piano di incremento della dose.
    • I/Le pazienti devono presentare un punteggio di Lansky (=16 anni di età) o Karnofsky (>16 anni di età) almeno pari a 50.
    E.4Principal exclusion criteria
    1. Pt has any of the following within 14 days before the first dose of study treatment: a. Platelet count <75 × 109/L (<100 × 109/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement. b. Absolute neutrophil count <1.0 × 109/L. c. Hemoglobin <8.0 g/dL with no RBC transfusion minor/=7 days prior to the measurement. d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × the upper limit of normal (ULN) for age; except in patients with tumor involvement of the liver who must not have AST and ALT >5 × ULN for age. e. Total bilirubin >1.5 mg/dL for age; and in presence of Gilbert's syndrome, total bilirubin >3 × ULN or direct bilirubin > 1.5 × ULN. f. Serum creatinine >1.5 × ULN for age. g. International normalized ratio or prothrombin time >ULN (>1.5 × ULN if on prophylactic reversible anticoagulants). 2. Pt has a QT interval corrected using Fridericia's formula (QTcF) >470 msec. Pt has a familial or personal history of prolonged QT syndrome or Torsades de pointes. 3. Pt has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the NYHA classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation. 4. Pt received the following systemic antineoplastic therapies: a. Systemic antineoplastic therapy. b. Focal external beam radiotherapy. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery. Craniospinal irradiation. c. All AEs related to other antineoplastic therapies must have resolved to Grade 1 (Grade = 2 for peripheral neuropathy and/or ototoxicity) prior to the first dose of avapritinib. 5. Pt has previously received treatment with avapritinib. 6. Pt received autologous stem cell transplant (SCT) following myeloablative therapy or chimeric antigen receptor T cell (CAR-T) therapy within 3 months prior to the first dose of avapritinib or prior allogeneic SCT at any time. Patients who received stem cell reinfusion following non-myeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1. 7. Pt requires ongoing treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers. 8. Pt has had a major surgical procedure within 14 days of the first dose of study treatment. 9. Pt has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. 10. Female subjects of childbearing potential who are unwilling, if not post-menopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Refer to Section 5.4.2 for acceptable methods of contraception. Please Refer to protocol for further information.
    1. Il paz presenta una qualsiasi delle seguenti condizioni nei 14 giorni precedenti la prima dose del trattamento dello studio: a. Conta piastrinica <75 × 109/l (<100 × 109/l in caso di tumore del SNC) senza trasfusione piastrinica nei 14 giorni precedenti la misurazione. b. Conta assoluta dei neutrofili <1,0 × 109/l. c. Emoglobina <8,0 g/dl senza trasfusione di globuli rossi minore/=7 giorni prima della misurazione. d. Aspartato aminotransferasi (AST) o alanina aminotransferasi (ALT) >3 × il limite superiore dell’intervallo normale (ULN) per età; tranne nei pazienti con coinvolgimento tumorale del fegato che non devono presentare AST e ALT >5 × ULN per età. e. Bilirubina totale >1,5 mg/dl per l’età e in presenza di sindrome di Gilbert, bilirubina totale >3 × ULN o bilirubina diretta >1,5 × ULN. f. Creatinina sierica >1,5 × ULN per età. g. Rapporto normalizzato internazionale o tempo di protrombina >ULN (>1,5 × ULN se in terapia profilattica con anticoagulanti reversibili). 2. Il paz ha un intervallo QT corretto utilizzando la formula di Fridericia (QTcF) >470 msec. Il paz presenta un’anamnesi familiare o personale di sindrome del QT lungo o torsione di punta. 3. Il paz presenta malattia cardiovascolare clinicamente significativa non controllata, inclusa insufficienza cardiaca congestizia di grado III o IV secondo la classificazione NYHA; infarto miocardico o angina instabile nei 6 mesi precedenti, ipertensione non controllata o aritmie clinicamente significative non controllate, comprese bradiaritmie che possono causare un prolungamento del QT. 4. Il paz ha ricevuto le seguenti terapie antineoplastiche sistemiche: a. Terapia antineoplastica sistemica. b. Radioterapia focale a fasci esterni, inclusa radiochirurgia stereotassica. Radiofarmaci sistemici, tra cui radiochirurgia non stereotassica. Irradiazione craniospinale. c. Tutti gli AE correlati ad altre terapie antineoplastiche devono essersi risolti al Grado 1 (Grado =2 per neuropatia periferica e/o ototossicità) prima della prima dose di avapritinib. 5. Il paz ha precedentemente ricevuto un trattamento con avapritinib. 6. Il paz è stato sottoposto a trapianto autologo di cellule staminali (SCT) dopo terapia mieloablativa o terapia con cellule T del recettore chimerico dell’antigene (CAR-T) nei 3 mesi precedenti la prima dose di avapritinib o precedente SCT allogenico in qualsiasi momento. I pazienti che hanno ricevuto una reinfusione di cellule staminali dopo la terapia non mieloablativa sono idonei una volta soddisfatti i criteri di conta ematica periferica nel Criterio di esclusione n. 1. 7. Il paz richiede un trattamento in corso o ha ricevuto un trattamento nei 28 giorni precedenti l’inizio della somministrazione di avapritinib con farmaci o alimenti che sono forti inibitori o induttori del CYP3A. 8. Il paz è stato sottoposto a una procedura chirurgica maggiore entro 14 giorni dalla prima dose del trattamento dello studio. 9. Il paz presenta un’anamnesi di un altro tumore maligno primario che è stato diagnosticato o ha richiesto una terapia nei 3 anni precedenti la prima dose di avapritinib. 10. Soggetti di sesso femminile in età fertile non disposti, se non in post-menopausa o chirurgicamente sterili, ad astenersi dai rapporti sessuali o ad adottare metodi contraccettivi altamente efficaci dal momento del consenso informato e per almeno 6 settimane dopo l’ultima dose del trattamento dello studio. Soggetti di sesso maschile non disposti, se non chirurgicamente sterili, ad astenersi dai rapporti sessuali o ad adottare metodi contraccettivi altamente efficaci dal momento del consenso informato e per almeno 6 settimane dopo l’ultima dose del trattamento dello studio. Fare riferimento alla Sezione 5.4.2 per i metodi contraccettivi accettabili. Per ulteriori informazioni fare riferimento al protocollo.
    E.5 End points
    E.5.1Primary end point(s)
    Determination of recommended Part 2 dose (Part 1)
    Objective Response Rate (Part 2)
    Determinazione della dose raccomandata per la Parte 2 (Parte 1)
    Tasso di risposta obiettiva (Parte 2)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Determination of recommended Part 2 dose (Part 1): up to 8 months
    2. Objective Response Rate (Part 2): up to 36 months
    1. Determinazione della dose raccomandata per la Parte 2 (Parte 1): fino a 8 mesi
    2. Tasso di risposta obiettiva (Parte 2): fino a 36 mesi
    E.5.2Secondary end point(s)
    1. Objective Response Rate (ORR) (Part 1 and 2)
    2. Rate and severity of adverse events (Part 1 and Part 2)
    3. Duration of Response (Part 2)
    4. Progression-free survival (Part 2)
    5. Disease control rate (Part 2)
    6. Cmax (Part 1 and Part 2)
    7. AUC(0-24) (Part 1 and Part 2)
    8. Tmax (Part 1)
    9. T 1/2 (Part 1)
    10. Ctrough (Part 2)
    1. Tasso di risposta obiettiva (ORR) (Parte 1 e Parte 2)
    2. Tasso e gravità di eventi avversi (Parte 1 e Parte 2)
    3. Durata della risposta (Parte 2)
    4. Sopravvivenza libera da progressione (Parte 2)
    5. Tasso di controllo della malattia (Parte 2)
    6. Concentrazione plasmatica massima (Cmax) (Parte 1 e Parte 2)
    7. Area sotto la curva di concentrazione plasmatica in funzione del tempo da 0 a 24 ore (AUC0-24) (Parte 1 e Parte 2)
    8. Tmax (Parte 1)
    9. T 1/2 (Parte 1)
    10. Ctrough (Parte 2)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Objective Response Rate (ORR) (Part 1 and 2) up to 42 months
    2. Rate and severity of adverse events (Part 1 and Part 2) up to 42 months
    3. Duration of Response (Part 2) : up to 42 months
    4. Progression-free survival (Part 2) up to 42 months
    5. Disease control rate (Part 2) : up to 42 months
    6. Cmax (Part 1 and Part 2) : up to 36 months
    7. AUC(0-24) (Part 1 and Part 2) : up to 36 months
    8. Tmax (Part 1): up to 36 months
    9. T 1/2 (Part 1): up to 36 months
    10. Ctrough (Part 2) : up to 36 months
    1. Tasso di risposta obiettiva (ORR) (Parte 1 e Parte 2) fino a 42 mesi
    2. Tasso e gravità di eventi avversi (Parte 1 e Parte 2) fino a 42 mesi
    3. Durata della risposta (Parte 2):fino a 42 mesi
    4. Sopravvivenza libera da progressione (Parte 2): fino a 42 mesi
    5. Tasso di controllo della malattia (Parte 2): fino a 42 mesi
    6. Concentrazione plasmatica massima (Cmax) (Parte 1 e Parte 2): fino a 36 mesi
    7. Area sotto la curva di concentrazione plasmatica in funzione del tempo da 0 a 24 ore (AUC0-24) (Parte 1 e Parte 2): fino a 36 mesi
    8. Tmax (Parte 1) fino a 36 mesi
    9. T 1/2 (Parte 1) fino a 36 mesi
    10. Ctrough (Parte 2) fino a 36 mesi
    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 No
    E.6.11Pharmacogenomic No
    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
    First in children study
    Studio prima somministrazione bambini
    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 No
    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 Yes
    E.8.1.7.1Other trial design description
    in aperto
    Open
    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 No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    Austria
    Canada
    Denmark
    France
    Germany
    Italy
    Korea, Republic of
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LPLV
    Ultima visita dell'ultimo soggetto
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years3
    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 Yes
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 26
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 11
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 No
    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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Minors
    Minori
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 9
    F.4.2.2In the whole clinical trial 37
    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)
    There is no limit to the duration of treatment in this study. Patients who discontinue treatment will be offered follow-up approximately every 3 months until death or loss to follow-up
    Non vi è alcun limite alla durata del trattamento in questo studio. Ai pazienti che interrompono il trattamento verrà offerto un follow-up circa ogni 3 mesi fino alla morte o alla perdita al follow-up
    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 Decision2022-03-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-12-21
    P. End of Trial
    P.End of Trial StatusOngoing
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