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    Summary
    EudraCT Number:2018-002551-15
    Sponsor's Protocol Code Number:8951-CL-5201
    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:2021-02-04
    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 number2018-002551-15
    A.3Full title of the trial
    A Phase 2, Open-Label, Randomized Study to Assess the Antitumor Activity and Safety of Zolbetuximab (IMAB362) in Combination with Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects with Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma
    Studio di fase 2, in aperto, randomizzato, volto a valutare l'attività antitumorale e la sicurezza di zolbetuximab (IMAB362) in combinazione con nab-paclitaxel e gemcitabina (Nab-P + GEM) come trattamento di prima linea in soggetti con adenocarcinoma pancreatico metastatico con positività a Claudina 18.2 (CLDN18.2)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial to evaluate a new medicine (Zolbetuximab) for the treatment of pancreatic cancer
    Sperimentazione clinica per valutare un nuovo farmaco (Zolbetuximab) per il trattamento del cancro del pancreas
    A.3.2Name or abbreviated title of the trial where available
    NA
    NA
    A.4.1Sponsor's protocol code number8951-CL-5201
    A.5.4Other Identifiers
    Name:INDNumber:129598
    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 SponsorASTELLAS PHARMA GLOBAL DEVELOPMENT, 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 supportAstellas Pahrma Global Develpment, Inc. (APGD)
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma Europe B.V.
    B.5.2Functional name of contact pointService Desk - Global Clinical Dev.
    B.5.3 Address:
    B.5.3.1Street AddressSylviusweg 62
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333 BE
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031715455878
    B.5.5Fax number0031715455224
    B.5.6E-mailcontacts@nl.astellas.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.2.1.1.1Trade name NA
    D.2.1.1.2Name of the Marketing Authorisation holderNA
    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/3/13/1177
    D.3 Description of the IMP
    D.3.1Product nameZolbetuximab
    D.3.2Product code [IMAB362]
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNZolbetuximab
    D.3.9.1CAS number 1496553-00-4
    D.3.9.2Current sponsor codeIMAB362
    D.3.9.3Other descriptive nameIMAB362
    D.3.9.4EV Substance CodeSUB190351
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number105
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeAnticorpo monoclonale
    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
    First Line Treatment in Subjects with Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma
    Trattamento di prima linea in soggetti con Claudin 18.2 (CLDN18.2) Adenocarcinoma del pancreas positivo e metastatico
    E.1.1.1Medical condition in easily understood language
    Pancreatic cancer
    Cancro del pancreas
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10033599
    E.1.2Term Pancreatic adenocarcinoma metastatic
    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
    -To confirm the recommended phase 2 dose (RP2D) of zolbetuximab in combination with Nab-P + GEM for subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma (Safety Lead-in Phase)
    -To determine antitumor activity of zolbetuximab measured by the OS in combination with Nab-P + GEM for subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma (Randomization Phase)
    -To assess the safety and tolerability of zolbetuximab in combination with Nab-P + GEM
    • Confermare la dose raccomandata della fase 2 (Recommended Phase 2 Dose, RP2D) di zolbetuximab in combinazione con Nab-P + GEM per i soggetti con adenocarcinoma pancreatico metastatico con positività a CLDN18.2 (fase preliminare di sicurezza).
    • Determinare l'attività antitumorale di zolbetuximab misurata tramite sopravvivenza globale (Overall Survival, OS) in combinazione con Nab-P + GEM per i soggetti con adenocarcinoma pancreatico metastatico con positività a CLDN18.2 (fase di randomizzazione).
    • Valutare la sicurezza e tollerabilità di zolbetuximab in combinazione con Nab-P + GEM.
    E.2.2Secondary objectives of the trial
    Key Secondary:
    ¿ To evaluate additional antitumor activities of zolbetuximab in combination with Nab-P + GEM measured by PFS and ORR
    (Randomization Phase)
    Secondary:
    ¿ To evaluate pharmacokinetics of Nab-P + GEM in combination with zolbetuximab (Randomization Phase)
    ¿ To evaluate additional antitumor activities measured by disease control rate (DCR) and duration of response (DOR) (Randomization Phase)
    ¿ To evaluate the change in serum CA19-9 (Randomization Phase)
    ¿ To evaluate pharmacokinetics and immunogenicity of zolbetuximab in combination with Nab-P + GEM
    Secondario principale:
    • Valutare le ulteriori attività antitumorali di zolbetuximab in combinazione con Nab-P + GEM tramite misurazione della sopravvivenza senza progressione (Progression Free Survival, PFS) e del tasso di risposta obiettiva (Objective Response Rate, ORR) (fase di randomizzazione).
    Secondari:
    • Valutare la farmacocinetica di Nab-P + GEM in combinazione con zolbetuximab (fase di randomizzazione).
    • Valutare le ulteriori attività antitumorali tramite misurazione del tasso di controllo della malattia (Disease Control Rate, DCR) e della durata della risposta (Duration of Response, DOR) (fase di randomizzazione).
    • Valutare la risposta del CA19-9 sierico (fase di randomizzazione).
    • Valutare la farmacocinetica e immunogenicità di zolbetuximab in combinazione con Nab P + GEM.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. written informed consent and privacy language as per national regulations (must be obtained from the subject or legally authorized representative prior to any study related procedures (including withdrawal of prohibited medication, if applicable).
    2. Subject is considered an adult according to local regulation at the time of signing informed consent.
    3. Subject agrees not to participate in another interventional study while receiving study drug in present study.
    4. A female subject is eligible to participate if she is not pregnant or lactating and at least 1 of the following conditions applies:
    ¿ Not a woman of childbearing potential (WOCBP) as defined in the Protocol.
    OR
    ¿ WOCBP who agrees to follow the contraceptive guidance as defined in the Protocol throughout the treatment period and for at least 6 months after the final study drug administration.
    5. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
    6. Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
    7. A male subject with female partner(s) of child-bearing potential must agree to use contraception as detailed in the Protocol during the treatment period and for at least 6 months after the final study drug administration.
    8. A male subject must not donate sperm during the treatment period and for at least 6 months after the final study drug administration.
    9. Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
    10. Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
    11. Subjects must have metastatic pancreatic cancer that has not been previously treated with chemotherapy.
    ¿ Prior treatment with 5-FU or GEM administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed (if there is lingering toxicity, then the sponsor should be consulted).
    ¿ If a subject received therapy in the adjuvant setting, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of adjuvant therapy.
    12. Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measureable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
    13. Subject's tumor sample has CLDN18.2 expression in = 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
    14. Subject has ECOG performance status of 0 or 1.
    15. Subject has predicted life expectancy = 12 weeks in the opinion of the investigator.
    16. Subject must meet all of the following criteria on the laboratory tests that will be analyzed centrally within 14 days prior to the first dose of study drug. In case of multiple laboratory data within this period, the most recent data should be used.
    •Hemoglobin = 9 g/dl (no transfusion within 14 days of start of study
    treatment)
    •Absolute neutrophil count = 1.5 x 109 /L
    •Platelets = 100 x 109 /L
    •Albumin = 2.5 g/dL
    •Total bilirubin = 1.5 x upper limit of normal (ULN)
    •Aspartate aminotransferase and alanine aminotransferase = 2.5 x ULN without liver metastases (= 5 x ULN if liver metastases are present)
    •Estimated creatinine clearance = 30 mL/min
    •Prothrombin time/international normalized ratio and partial thromboplastin time = 1.5 x ULN (except for subjects receiving
    anticoagulation therapy)
    1. Prima che venga eseguita una qualunque procedura correlata allo studio deve essere ottenuto dal soggetto o dal suo rappresentante legalmente autorizzato il consenso informato scritto e deve essere stata firmata l'informativa sulla privacy
    2. Al momento della firma del consenso informato, il soggetto è considerato adulto ai sensi della normativa locale.
    3. I soggetti devono accettare di non partecipare ad altri studi interventistici mentre ricevono il farmaco in studio nell'ambito del presente studio.
    4. Un soggetto di sesso femminile è idoneo a partecipare se non è in gravidanza o in allattamento [consultare l'Appendice 12.3 Requisiti sulla contraccezione] ed è applicabile almeno 1 delle condizioni seguenti:
    • Non è una donna in grado di procreare (Woman Of ChildBearing Potential, WOCBP) come definito nella [Appendice 12.3 Requisiti sulla contraccezione] oppure:
    • Si tratta di una WOCBP che accetta di utilizzare un metodo contraccettivo come definito nella [Appendice 12.3 Requisiti sulla contraccezione] durante l'intero periodo di trattamento e per almeno 6 mesi dopo la somministrazione finale del farmaco in studio.
    5. I soggetti di sesso femminile devono accettare di non allattare al seno a partire dallo screening, per l'intero periodo dello studio e per i 6 mesi successivi alla somministrazione finale del farmaco in studio.
    6. I soggetti di sesso femminile non devono donare gli ovuli partire dallo screening, per l'intero periodo dello studio e per i 6 mesi successivi alla somministrazione finale del farmaco in studio.
    7. Un soggetto di sesso maschile, assieme alla/e propria/e partner di sesso femminile in grado di procreare, deve accettare di utilizzare dei metodi contraccettivi,
    8. I soggetti di sesso maschile non devono donare lo sperma durante il periodo di trattamento e per i 6 mesi successivi alla somministrazione finale del farmaco in studio.
    9. I soggetti di sesso maschile, assieme alla/e propria/e partner di sesso femminile in gravidanza o in allattamento, devono accettare di praticare l'astinenza o di utilizzare un preservativo per l'intera durata della gravidanza o dell'allattamento, per l'intero periodo dello studio e per 6 mesi successivi alla somministrazione finale del farmaco in studio
    10. Soggetti con adenocarcinoma del pancreas confermato tramite esami istologici o citologici.
    11. I soggetti devono avere un cancro metastatico del pancreas che non sia stato precedentemente trattato con chemioterapia.
    • È ammesso un trattamento precedente con 5-FU o gemcitabina (GEM) somministrate come sensibilizzante alle radiazioni durante e fino a 4 settimane dopo la radioterapia (in caso di tossicità persistente, consultare lo Sponsor).
    • Se un soggetto è stato sottoposto a terapia come trattamento adiuvante, la recidiva tumorale o la progressione della malattia devono essere avvenute almeno 6 mesi dopo il completamento dell'ultima dose di terapia adiuvante.
    12. I soggetti devono presentare lesione/i misurabile/i in almeno 1 sede metastatica, Per i soggetti con una sola lesione misurabile e che siano stati sottoposti in precedenza a radioterapia, la lesione deve essere al di fuori dell'area sottoposta in precedenza a radioterapia o deve avere una progressione documentata dopo la radioterapia.
    13. Il campione di tumore del soggetto presenta espressione di CLDN18.2 nel = 75% delle cellule tumorali, con colorazione membranosa da moderata a forte, come determinato dal test IHC condotto a livello centrale.
    14. Il soggetto ha un performance status ECOG di 0 o 1.
    15. Il soggetto ha una previsione di aspettativa di vita = 12 settimane, secondo il parere dello Sperimentatore.
    16. Il soggetto deve soddisfare tutti i seguenti criteri relativi agli esami di laboratorio che saranno analizzati a livello centrale
    E.4Principal exclusion criteria
    Subject will be excluded from participation if any of the following apply:
    Prohibited Treatment or Therapies
    1. Subject has received other investigational treatment within 28 days
    prior to screening.
    2. Subject has received radiotherapy for metastatic pancreatic adenocarcinoma within 28 days prior to the first dose of study
    treatment. Subject who received palliative radiotherapy to peripheral bone metastases = 14 days prior to first dose of study treatment and has recovered from all acute toxicities is eligible.
    3. Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment.
    Subject using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) or a single dose of systemic corticosteriods is eligible.
    4. Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibody, including humanized or chimeric antibodies.
    5. Subject has known immediate or delayed hypersensitivity, intolerance
    or
    contraindication to any component of study treatment.
    6. Subject has a known history of a positive test for human immunodeficiency virus infection or known active Hepatitis B (positive HBs antigen [Ag]) or Hepatitis C infection. For subjects who are negative for HBs Ag, but Hepatitis B core antibody positive, a Hepatitis B virus DNA test will be performed and if positive, the subject will be excluded. Subjects with
    positive serology but negative Hepatitis C virus RNA test results are eligible.
    7. Subject has a history of interstitial pneumonia or pulmonary fibrosis.
    8. Subject has pleural effusion or ascites = Grade 3 per CTCAE v 4.0.
    9. Subject has an active autoimmune disease that has required systemictreatment in the past 2 years.
    10. Subject has active infection requiring systemic therapy that has not completely resolved per investigator judgment within 14 days prior to first dose of study treatment.
    11. Subject has significant cardiovascular disease, including:
    ¿ Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to administration of first dose of study treatment;
    ¿ History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
    ¿ QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects;
    ¿ Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects
    with rate controlled atrial fibrillation for > 1 month prior to first dose of study
    treatment are eligible.)
    12. Subject has known active or treated central nervous system metastases and/or carcinomatous meningitis.
    13. Subject has known peripheral sensory neuropathy = Grade 2 per CTCAE v.4.0 unless the absence of deep tendon reflexes is the sole neurological abnormality.
    14. Subject has had a major surgical procedure = 28 days prior to the first dose of study drug.
    15. Subject without complete recovery from a major surgical procedure = 14 days prior to the first dose of study treatment.
    16. Psychiatric illness or social situations that would preclude study compliance per investigator's judgment.
    17. Subject has another malignancy for which treatment is required per investigator's clinical judgment.
    18. Subject has any concurrent disease, infection or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.
    1. Soggetti che abbiano ricevuto un altro trattamento sperimentale nei 28 giorni antecedenti allo screening.
    2. Soggetti sottoposti a radioterapia per l'adenocarcinoma metastatico del pancreas nei 28 giorni antecedenti la somministrazione della prima dose del trattamento dello studio.
    3. Soggetti sottoposti a terapia immunosoppressiva sistemica, compreso l'uso di corticosteroidi sistemici nei 14 giorni antecedenti la somministrazione della prima dose del trattamento dello studio. I soggetti che utilizzano una dose sostitutiva fisiologica di idrocortisone o un suo equivalente (definita come max 30 mg/die di idrocortisone o max 10 mg/die di prednisone) o una singola dose di corticosteroidi sistemici sono idonei.
    4. Soggetti che abbiano avuto in precedenza gravi reazioni allergiche o intolleranze agli ingredienti noti di zolbetuximab o ad altri anticorpi monoclonali, compresi anticorpi umanizzati o chimerici.
    5. Soggetti con ipersensibilità a insorgenza immediata o tardiva, intolleranza, o controindicazione note a qualsiasi componente del trattamento di studio.
    6. Soggetti con anamnesi nota di positività al test per l'infezione da virus dell'immunodeficienza umana o infezione nota attiva da epatite B (positività all'antigene HBsAg) o Epatite C. Per i soggetti con negatività all’HBsAg, ma con positività all’anticorpo contro l'antigene del core virale dell’epatite B, verrà eseguito un test del DNA del virus dell'epatite B e, se positivo, i soggetti saranno esclusi. I soggetti con sierologia positiva ma risultati negativi del test dell'RNA del virus dell'Epatite C sono idonei.
    7. Soggetti con precedenti episodi di polmonite interstiziale o fibrosi polmonare.
    8. Soggetti con versamento pleurico o ascite di grado = 3 secondo i criteri CTCAE v4.0.
    9. Soggetti con malattia autoimmune attiva per cui negli ultimi 2 anni sia stato necessario un trattamento sistemico.
    10. Soggetti affetti da infezione attiva che richiede una terapia sistemica e che, secondo il parere dello Sperimentatore, non si sia completamente risolta nei 14 giorni antecedenti la somministrazione della prima dose del trattamento dello studio.
    11. Soggetti con cardiovasculopatie significative, tra cui:
    a. Scompenso cardiaco congestizio (definito come di Classe III o IV secondo la New York Heart Association), infarto del miocardio, angina instabile, angioplastica coronarica, stent coronarico, innesto di bypass coronarico, accidente cerebrovascolare o crisi ipertensiva nei 6 mesi antecedenti la somministrazione della prima dose di trattamento dello studio.
    b. Precedenti aritmie ventricolari significative da un punto di vista clinico (ossia tachicardia ventricolare sostenuta, fibrillazione ventricolare o torsione di punta).
    c. Intervallo QTc > 450 msec per i soggetti di sesso maschile; intervallo QTc > 470 msec per i soggetti di sesso femminile.
    d. Aritmie cardiache che richiedano farmaci antiaritmici (soggetti con fibrillazione atriale con frequenza controllata per > 1 mese prima della somministrazione della prima dose del trattamento dello studio sono idonei).
    12. Soggetti con metastasi note attive o trattate del sistema nervoso centrale e/o meningite carcinomatosa.
    13. Soggetti con neuropatia sensoriale periferica nota di grado = 2 come da criteri CTCAE v.4.0 a meno che l'assenza di riflessi tendinei profondi sia l'unica anomalia neurologica.
    14. Soggetti sottoposti a procedura chirurgica importante = 28 prima della somministrazione della prima dose del farmaco in studio.
    15. Soggetti che non hanno avuto un recupero completo da una procedura chirurgica importante = 14 prima della somministrazione della prima dose del trattamento dello studio
    16. Malattie psichiatriche o situazioni sociali che, secondo il parere dello Sperimentatore, precluderebbero l'osservanza dei requisiti dello studio.
    17. Soggetti con un'altra patologia maligna per la quale, secondo il parere clinico dello Sperimentatore, sia necessario un trattamento.
    E.5 End points
    E.5.1Primary end point(s)
    ¿ Confirm RP2D as assessed by DLTs (Safety Lead-in Phase)
    ¿ Safety and tolerability as measured by AEs, laboratory test results, vital signs, ECGs and ECOG performance status.
    ¿ OS, defined as the time from the date of randomization until the date of death from any cause
    • Conferma della RP2D, come valutato dalle DLT (fase preliminare di sicurezza).
    • Sicurezza e tollerabilità, misurate tramite EA, risultati delle analisi di laboratorio, parametri vitali, ECG e performance status ECOG.
    • OS, definita come il periodo di tempo che intercorre tra la data di randomizzazione e il decesso per qualsiasi causa.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoints will be evaluated at the time of interim analysis.
    All endpoints will be evaluated at primary analysis. A futility analysis will be conducted by the IDMC when 42 OS events are observed. The primary analysis will occur once 83 OS events have been observed.
    Gli endpoint primari saranno valutati al momento dell'analisi provvisoria.
    Tutti gli endpoint saranno valutati all'analisi primaria. Un'analisi della futilità sarà condotto da IDMC quando verranno osservati 42 eventi del sistema operativo. Il l'analisi primaria si verificherà una volta che siano stati osservati 83 eventi del sistema operativo.
    E.5.2Secondary end point(s)
    PFS, defined as the time from the date of randomization until the date of radiological PD per RECIST 1.1 by local investigator evaluation, or
    death from any cause, whichever is earliest
    ¿ ORR, defined as the proportion of subjects who have a best overall
    response of CR or PR as assessed by local investigator evaluation per
    RECIST 1.1
    Secondary:
    ¿ Pharmacokinetic parameters of zolbetuximab, Nab-P (measured as
    PTX) and GEM (AUCinf, AUCinf [%extrap], AUClast, Cmax, Ctrough,
    tmax, t1/2, , tlast,
    CL, Vz, as appropriate)
    ¿ DCR, defined as the proportion of subjects who have a best overall
    response of CR, PR or stable disease (SD) as assessed by local
    investigator evaluation per
    RECIST 1.1
    ¿ DOR, defined as the time from the date of the first response (CR/PR)
    until the date of PD as assessed by local investigator evaluation per
    RECIST 1.1 or date of
    death from any cause, whichever is earliest
    ¿ Serum CA19-9 change from baseline
    ¿ Immunogenicity of zolbetuximab as measured by the frequency of
    anti-drug antibody (ADA) positive subjects
    The primary and key secondary endpoints will be evaluated at the time
    of interim analysis.
    All endpoints will be evaluated at primary analysis.
    • PFS, definita come il periodo di tempo che intercorre tra la data di randomizzazione e la data di progressione radiologica della malattia (PD) secondo i criteri RECIST 1.1 mediante valutazione dello Sperimentatore locale, oppure fino alla data del decesso per qualsiasi causa, a seconda di quale dei due eventi si verifichi per primo.
    • ORR, definito come la percentuale di soggetti che presenta, come migliore risposta globale, una risposta completa (CR) o una PR, come valutato da parte dello Sperimentatore locale secondo i criteri RECIST 1.1.
    Secondari:
    • Parametri farmacocinetici di zolbetuximab, Nab-P (misurati come paclitaxel, (PTX)) e GEM (AUCinf, AUCinf [%extrap], AUCult.con.mis., Cmax, Cmin, tmax, t1/2, tult.con.mis., CL, Vz, come appropriato).
    • DCR, definito come la percentuale di soggetti che presenta una migliore risposta globale di malattia stabile, CR o PR, come valutato dallo Sperimentatore locale secondo i criteri RECIST 1.1.
    • DOR, definita come il periodo di tempo che intercorre tra la prima risposta (CR/PR) e la data di PD, come valutato dallo Sperimentatore locale secondo i criteri RECIST 1.1, oppure fino alla data del decesso per qualsiasi causa, a seconda di quale dei due eventi si verifichi per primo.
    • Variazione rispetto al basale del CA19-9 sierico.
    • Immunogenicità di zolbetuximab misurata in base alla frequenza dei soggetti positivi agli anticorpi anti-farmaco (ADA, anti-drug antibodies)
    E.5.2.1Timepoint(s) of evaluation of this end point
    The key secondary endpoints will be evaluated at the time of interim
    analysis.
    All endpoints will be evaluated at primary analysis. A futility analysis will be conducted by the IDMC when 42 OS events are observed. The primary analysis will occur once 83 OS events have been observed
    Gli endpoint secondari chiave verranno valutati al momento dell'intermedio
    analisi.
    Tutti gli endpoint saranno valutati all'analisi primaria. Un'analisi della futilità sarà condotto da IDMC quando verranno osservati 42 eventi del sistema operativo. Il l'analisi primaria si verificherà una volta che siano stati osservati 83 eventi del sistema operativo
    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 No
    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) 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 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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA44
    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
    France
    Germany
    Ireland
    Italy
    Japan
    Korea, Democratic People's Republic of
    Spain
    Taiwan
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The last visit or scheduled procedure for the last study participant in the study
    L'ultima visita o la procedura programmata per l'ultimo partecipante allo studio
    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: 47
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 94
    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 state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 61
    F.4.2.2In the whole clinical trial 132
    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)
    Zolbetuximab may be made available after the conclusion of the study to subjects who are still receiving and benefiting from study treatment until study defined treatment discontinuation criterion is met.
    Zolbetuximab può essere reso disponibile dopo la conclusione dello studio ai soggetti che stanno ancora ricevendo e beneficiando del trattamento di studio fino a quando lo studio ha definito che il criterio di sospensione del trattamento è soddisfatto.
    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 Decision2019-11-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-12-11
    P. End of Trial
    P.End of Trial StatusOngoing
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