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    Summary
    EudraCT Number:2015-000319-41
    Sponsor's Protocol Code Number:RPC01-3101
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-01-29
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-000319-41
    A.3Full title of the trial
    A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Oral RPC1063 as Induction and Maintenance Therapy for Moderate to Severe Ulcerative Colitis.
    Studio di fase 3, multicentrico, randomizzato, in doppio cieco, controllato con placebo, di RPC1063 per uso orale come terapia di induzione e mantenimento per la colite ulcerosa da moderata a grave.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The purpose of this study is to determine whether RPC1063 is safe and effective in the treatment of ulcerative colitis (UC).
    Sperimentazione per valutare la sicurezza e l¿efficacia di RPC1063 per la colite ulcerosa da moderata a grave
    A.3.2Name or abbreviated title of the trial where available
    Efficacy and Safety Study of RPC1063 in Ulcerative Colitis
    Sperimentazione per valutare la sicurezza e l¿efficacia di RPC1063 per la colite ulcerosa
    A.4.1Sponsor's protocol code numberRPC01-3101
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01647516
    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 SponsorCELGENE INTERNATIONAL II SàRL
    B.1.3.4CountrySwitzerland
    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 supportCelgene International II S¿rl (CIS II)
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCelgene International II Sàrl
    B.5.2Functional name of contact pointTruenorth Study Information Center
    B.5.3 Address:
    B.5.3.1Street Address3033 Science Park Road, Suite 300
    B.5.3.2Town/ citySan Diego, California
    B.5.3.3Post code92121
    B.5.3.4CountryUnited States
    B.5.4Telephone number0018586255705
    B.5.5Fax number0018586255705
    B.5.6E-mailtruenorth@quintiles.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 name0.25 mg RPC103
    D.3.2Product code RPC1063
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOzanimod
    D.3.9.2Current sponsor codeRPC1063
    D.3.9.3Other descriptive name(S)-5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride
    D.3.9.4EV Substance CodeSUB175614
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    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 name1.0 mg RPC103
    D.3.2Product code RPC1063
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNA
    D.3.9.2Current sponsor codeRPC1063
    D.3.9.3Other descriptive name(S)-5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride
    D.3.9.4EV Substance CodeSUB175614
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number1000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Ulcerative Colitis
    Colite Ulcerosa
    E.1.1.1Medical condition in easily understood language
    Ulcerative Colitis
    Colite Ulcerosa
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10045365
    E.1.2Term Ulcerative colitis
    E.1.2System Organ Class 100000004856
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    INDUCTION THERAPY
    Demonstrate the efficacy of RPC1063 versus placebo on induction of clinical remission.
    MAINTENANCE THERAPY
    To demonstrate the efficacy of RPC1063 versus placebo maintenance therapy on clinical remission.
    PERIODO DI INDUZIONE: Dimostrare l¿efficacia di RPC1063 rispetto al placebo sull¿induzione della remissione clinica.
    PERIODO DI MANTENIMENTO: Dimostrare l¿efficacia di RPC1063 rispetto alla terapia di mantenimento con placebo sulla remissione clinica.
    E.2.2Secondary objectives of the trial
    INDUCTION THERAPY
    Demonstrate
    -the efficacy of RPC1063 versus placebo on induction of clinical response
    -the efficacy of RPC1063 versus placebo on achieving endoscopic improvement
    -the efficacy of RPC1063 versus placebo on achieving histologic remission
    -the safety and tolerability of RPC1063 induction therapy
    MAINTENANCE THERAPY
    Demonstrate
    -the efficacy of RPC1063 versus placebo in maintaining clinical response
    -the efficacy of RPC1063 versus placebo on achieving endoscopic improvement
    -the efficacy of RPC1063 versus placebo on durability of clinical remission
    -the efficacy of RPC1063 versus placebo on maintaining clinical remission among patients who achieved remission during induction therapy
    -the efficacy of RPC1063 versus placebo, in achieving corticosteroid-free remission among patients receiving corticosteroids at entry into the
    Maintenance Period
    -the safety and tolerability of RPC1063 maintenance therapy
    PERIODO DI INDUZIONE DIMOSTRARE:
    -l¿efficacia di RPC1063 rispetto al placebo sull¿induzione della risposta clinica
    -l¿efficacia di RPC1063 rispetto al placebo sul raggiungimento del miglioramento endoscopico
    -l¿efficacia di RPC1063 rispetto al placebo sul raggiungimento della remissione istologica
    -la sicurezza e la tollerabilit¿ della terapia di induzione con RPC1063
    PERIODO DI MANTENIMENTO DIMOSTRARE:
    -l¿efficacia di RPC1063 rispetto al placebo nel mantenere la risposta clinica
    -l¿efficacia di RPC1063 rispetto al placebo sul raggiungimento del miglioramento endoscopico
    -l¿efficacia di RPC1063 rispetto al placebo sulla durata della remissione clinica
    -l¿efficacia di RPC1063 rispetto al placebo nel mantenere la remissione clinica tra i pazienti che hanno raggiunto la remissione durante l'induzione
    -efficacia di RPC1063 rispetto al placebo, nel raggiungere la remissione senza corticosteroidi al momento dell¿ingresso nel mantenimento
    -sicurezza e tollerabilit¿ del mantenimeto con RPC1063
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female patients aged 18 to 75 years (at screening), inclusive
    2. Have had UC diagnosed at least 3 months prior to first investigational
    drug administration. The diagnosis should be confirmed by clinical and
    endoscopic evidence and corroborated by a histopathology report (note:
    endoscopy and histopathology may be performed at Screening if no prior
    report is readily available)
    3. Evidence of UC extending = 15 cm from the anal verge as determined
    by Baseline endoscopy (flexible sigmoidoscopy or colonoscopy)
    4. Have active UC defined as Mayo score of 6 to 12 inclusive, with
    endoscopic subscore of = 2, a rectal bleeding score of = 1, and a stool
    frequency score = 1
    5. Must be currently receiving treatment with at least 1 of the following
    therapies and must continue on these therapies during Induction:
    - Oral aminosalicylates at a therapeutic dose for their disease (eg,
    mesalamine, sulfasalazine, olsalazine, balsalazide), with the dose stable
    for at least 3 weeks, prior to Screening endoscopy
    - Prednisone (doses = 20 mg per day) or equivalent receiving a stable
    dose for at least 2 weeks prior to Screening endoscopy
    - Budesonide MMX therapy receiving a stable dose for at least 2 weeks
    prior to Screening endoscopy
    6. Have undergone colonoscopy (or are willing to undergo colonoscopy
    during Screening):
    - within the past 2 years, to screen for dysplasia (unless otherwise
    recommended by local and national guidelines) if the patient has had
    left-sided colitis of > 12 years duration or total/extensive colitis of > 8
    years duration
    - within the past 5 years, to screen for polyps if the patient age is > 45
    years
    7. If oral aminosalicylates or corticosteroids have been recently
    discontinued, they must have been stopped for at least 2 weeks prior to
    the endoscopy used for Baseline Mayo score
    8. Males and females of childbearing potential must agree to use
    adequate birth control measures during the trial. Acceptable methods of
    birth control in this trial include: surgical sterilization, intrauterine
    device, oral contraceptive, contraceptive patch, long-acting injectable
    contraceptive, partner's vasectomy, double-barrier method
    (condom or diaphragm with spermicide or condom with diaphragm), or
    abstinence during trial participation and for 30 days after their last dose
    of study drug. Sites must use the most stringent form of birth control as
    specified by local regulations, including directions from ethics
    committees and regulatory bodies if provided.
    9. Provide written informed consent and to be compliant with the
    schedule of protocol assessments
    10. Patients must have documentation of positive Varicella zoster virus
    IgG antibody status or complete Varicella zoster virus vaccination at
    least 30 days prior to randomization
    1. Pazienti di sesso maschile o femminile di età compresa tra 18 e 75 anni, inclusi (allo screening)
    2. Diagnosi di CU effettuata almeno 3 mesi prima della prima somministrazione del farmaco sperimentale. La diagnosi deve essere confermata da evidenze cliniche ed endoscopiche e corroborata da referto istopatologico (nota: l’endoscopia e l’esame istopatologico possono essere eseguiti allo screening, nel caso in cui non sia disponibile un referto precedente)
    3. Evidenze di CU che si estende per = 15 cm dal margine anale come stabilito mediante endoscopia al basale (sigmoidoscopia flessibile o colonscopia)
    4. Avere una CU attiva definita con un punteggio Mayo di 6-12 inclusi, un sottopunteggio endoscopico = 2, un sottopunteggio di sanguinamento rettale = 1 e un sottopunteggio di frequenza delle feci = 1
    5. Devono essere attualmente in trattamento con almeno 1 delle seguenti terapie e devono continuare tali terapie durante l’Induzione:
    ¿ Aminosalicilati orali alla dose terapeutica per la malattia (ad esempio, mesalazina, sulfasalazina, olsalazina, balsalazide), con la dose stabile per almeno 3 settimane, prima dell’endoscopia allo screening
    - Prednisone (dosi = 20 mg al giorno) o equivalente ricevuto a una dose stabile per almeno 2 settimane prima dell’endoscopia effettuata allo screening
    - Terapia con budesonide MMX ricevuta a una dose stabile per almeno 2 settimane prima dell’endoscopia effettuata allo screening.
    6.Essere stato/a sottoposto/a a una colonscopia (o essere disposto/a a essere sottoposto/a a una colonscopia durante lo screening):
    - nei 2 anni precedenti, per eseguire uno screening della displasia (se non diversamente raccomandato dalle linee guida locali e nazionali), nel caso in cui il/la paziente presenti una colite sinistra da > 12 anni o una colite totale/estesa da > 8 anni
    - nei 5 anni precedenti, per eseguire uno screening dei polipi se il/la paziente ha un’età > 45 anni
    Essere stato/a sottoposto/a a una colonscopia (o essere disposto/a a essere sottoposto/a a una colonscopia durante lo screening):
    - nei 2 anni precedenti, per eseguire uno screening della displasia (se non diversamente raccomandato dalle linee guida locali e nazionali), nel caso in cui il/la paziente presenti una colite sinistra da > 12 anni o una colite totale/estesa da > 8 anni
    - nei 5 anni precedenti, per eseguire uno screening dei polipi se il/la paziente ha un’età > 45 anni
    7. Se gli aminosalicilati orali o i corticosteroidi sono stati recentemente sospesi, devono essere stati interrotti per almeno 2 settimane prima dell’endoscopia utilizzata per il punteggio Mayo al basale.
    8. I soggetti di sesso maschile e femminile fertili devono acconsentire all’adozione di metodi contraccettivi accettabili durante la sperimentazione. I metodi contraccettivi accettabili in questa sperimentazione includono: sterilizzazione chirurgica, dispositivo intrauterino, contraccettivo orale, cerotto contraccettivo, contraccettivo iniettabile a lunga durata d’azione, vasectomia del compagno, metodo di doppia barriera (preservativo o diaframma con spermicida o preservativo con diaframma) o astinenza durante la partecipazione alla sperimentazione e per 30 giorni successivi all’ultima dose del farmaco sperimentale. I centri devono utilizzare la forma di contraccezione più rigorosa come specificato dalle normative locali, tra cui le indicazioni dei comitati etici e degli organismi di regolamentazione, se fornite.
    . Possibilità di fornire il consenso informato scritto e di essere conforme al programma di valutazioni del protocollo.
    10. I/Le pazienti devono disporre della documentazione attestante lo stato di positività agli anticorpi del tipo immunoglobuline G (IgG) per il virus Varicella zoster (varicella zoster virus, VZV) o la vaccinazione completa per il VZV almeno 30 giorni prima della randomizzazione
    E.4Principal exclusion criteria
    Exclusions Related to General Health:
    1. Have severe extensive colitis as evidenced by:
    • Physician judgment that the patient is likely to require colectomy or
    ileostomy within 12 weeks of Baseline
    • Current or recent (within 3 months) evidence of fulminant colitis, toxic
    megacolon, or bowel perforation
    2. Diagnosis of Crohn's disease or indeterminate colitis or the presence
    or history of a fistula consistent with Crohn's disease or microscopic
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    colitis or radiation colitis or ischemic colitis
    3. Have positive stool examination for pathogens (ova and parasites,
    bacteria) or positive test for toxin producing Clostridium difficile (C.
    difficile) at Screening. PCR
    (polymerase chain reaction) examination of the stool for C. difficile may
    be used to exclude false positives. If positive, patients may be treated
    and retested. Documentation of a negative test result for pathogens (ova
    and parasites, bacteria) is required within 60 days of Day 1.
    4. Pregnancy, lactation, or a positive serum ß-human chorionic
    gonadotropin (ß-hCG) measured during Screening
    5. Clinically relevant hepatic, neurological, pulmonary, ophthalmological,
    endocrine, psychiatric, or other major systemic disease making
    implementation of the protocol or interpretation of the trial difficult or
    that would put the patient at risk by participating in the trial
    presence of:
    • Recent (within the last 6 months) occurrence of myocardial infarction,
    unstable angina, stroke, transient ischemic attack, decompensated heart
    failure requiring hospitalization, Class III/IV heart failure, sick sinus
    syndrome, or severe untreated sleep apnea
    • Prolonged Fridericia's corrected QT interval (QTcF; QTcF > 450 msec
    for males, > 470 msec for females), or at additional risk for QT interval
    prolongation (eg, hypokalemia, hypomagnesemia, congenital long-QT
    syndrome, concurrent therapy with QT prolonging drugs)
    • Resting HR < 55 bpm when taking vital signs as part of a physical
    exam at Screening
    7. History of diabetes mellitus type 1, or uncontrolled diabetes mellitus
    type 2 with glycosylated Hb (HbA1c) > 9% , or diabetic patients with
    significant comorbid conditions such as retinopathy or nephropathy
    8. History of uveitis (within the last year) or macular edema
    9. Known active bacterial, viral, fungal, mycobacterial infection, or other
    infection (including tuberculosis [TB] or atypical mycobacterial disease
    [but excluding fungal infection of nail beds, minor upper respiratory
    tract infections and minor skin infections]) or any major episode of
    infection that required hospitalization or treatment with intravenous
    antibiotics within 30 days of Screening or oral antibiotics within 14 days
    of Screening
    10. History of cancer, including solid tumors and hematological
    malignancies (except basal cell and in situ squamous cell carcinomas of
    the skin or uterine cervix that have been excised and resolved) or
    colonic mucosal dysplasia
    11. History of alcohol or drug abuse within 1 year prior to randomization
    11. History of alcohol or drug abuse within 1 year prior to randomization
    Exclusions Related to Medications:
    12. History of treatment with a biologic agent within 10 weeks or 5
    elimination half-lives (whichever is less) of that agent prior to
    randomization
    13. History of treatment with an investigational agent within 5
    elimination half-lives of that agent prior to randomization
    14. History of treatment with topical rectal 5-aminosalicylic acid or
    topical rectal steroids within 2 weeks of Screening endoscopy or antimotility
    medications (such as diphenoxylate/atropine) during Screening
    15. Receipt of a live vaccine within 4 weeks prior to randomization
    16. Planned concurrent treatment with immunosuppressive agents (eg,
    AZA, 6-MP, or methotrexate) after randomization. Patients receiving
    AZA,6-MP, or methotrexate at
    Screening must discontinue treatment with these agents prior to
    randomization
    1. Avere una grave colite estesa come evidenziato da: -Parere medico che il/la paziente richieda probabilmente una colectomia o un’ileostomia nelle 12 settimane precedenti il basale -Evidenza attuale o recente (entro 3 mesi) di colite fulminante, megacolon tossico o perforazione intestinale
    2. Diagnosi di malattia di Crohn o colite indeterminata o presenza o anamnesi di una fistola compatibile con malattia di Crohn o colite microscopica o colite da radiazioni o colite ischemica
    3. Presentare allo screening un esame delle feci positivo ai patogeni (uova e parassiti, batteri) o un test positivo al Clostridium difficile (C. difficile) che produce tossine. L’esame della reazione a catena della polimerasi (polymerase chain reaction, PCR) del C. difficile nelle feci può essere utilizzato per escludere falsi positivi. Se positivi/e, i/le pazienti devono essere trattati/e e sottoposti/e nuovamente all’esame. È richiesta la documentazione di un risultato negativo all’esame riguardante i patogeni (uova e parassiti, batteri) entro 60 giorni dal Giorno 1.
    4. Gravidanza, allattamento o positività all’esame su siero della subunità ß della gonadotropina corionica umana (ß-human chorionic gonadotropin, ß-hCG) durante screening
    5. Malattia epatica, neurologica, polmonare, oftalmologica, endocrina, psichiatrica clinicamente rilevante o altre importanti malattie sistemiche che rendono difficile attuazione del protocollo o interpretazione della sperimentazione o che metterebbero il/la paziente a rischio con la partecipazione allo studio
    6. Condizioni cardiovascolari clinicamente rilevanti, tra cui anamnesi o presenza di:
    -Recente (negli ultimi 6 mesi) insorgenza infarto miocardico, angina instabile, ictus, attacco ischemico transitorio, scompenso cardiaco richiedente ricovero, insufficienza cardiaca classe III/IV, sindrome seno malato o grave apnea sonno non trattata
    -Prolungamento intervallo QT corretto secondo Fridericia (QTcF; QTcF > 450 ms per maschi, > 470 ms per femmine) o rischio aggiuntivo prolungamento intervallo QT (es. ipopotassiemia, ipomagnesiemia, sindrome congenita QT lungo, terapia concomitante con farmaci per prolungamento QT)
    -Frequenza cardiaca (heart rate, HR) a riposo < 55 battiti per minuto (bpm) durante rilevazione segni vitali come parte di 1 esame obiettivo allo screening
    7. Anamnesi diabete mellito tipo 1 o diabete mellito tipo 2 non controllato con emoglobina (hemoglobin, Hb) glicosilata (HbA1c) > 9% o pazienti diabetici con significative comorbilità come retinopatia o nefropatia
    8.Anamnesi di uveite (nell’anno precedente) o di edema maculare
    9. Nota infezione batterica, virale, micotica, micobatterica attiva o altra infezione (tra cui tubercolosi [TB] o malattia micobatterica atipica [con esclusione infezione micotica del letto ungueale, delle infezioni minori delle vie respiratorie superiori e delle infezioni cutanee minori]) o qualsiasi episodio di infezione richiedente ricovero o trattamento con antibiotici per via endovenosa entro 30 gg da screening o con antibiotici per via orale nei 14 gg precedenti screening
    10. Anamnesi cancro, compresi tumori solidi e neoplasie ematologiche (ad eccezione del carcinoma cutaneo a cellule basali e carcinoma cutaneo a cellule squamose in situ o carcinoma della cervice uterina escissi e risolti) o displasia della mucosa del colon
    11. Anamnesi abuso di alcol o sostanze stupefacenti entro 1 anno da randomizzazione
    12. Anamnesi di trattamento con un agente biologico nelle 10 settimane o 5 emivite di eliminazione (in base a quale periodo dura di meno) di tale agente prima della randomizzazione
    13. Anamnesi trattamento con 1 agente sperimentale entro 5 emivite di eliminazione di tale agente precedenti randomizzazione
    14. Anamnesi di trattamento con acido 5-aminosalicilico per uso topico rettale o steroidi rettali per uso topico nelle 2 settimane precedenti l’endoscopia effettuata allo screening o farmaci antimotilità (come difenossilato/atropina) durante lo screening
    E.5 End points
    E.5.1Primary end point(s)
    The efficacy endpoints will be formally examined with statistical
    hypothesis tests conducted on the efficacy results obtained from
    patients randomized and dosed in Cohort 1. Cohort 2 is open-label and
    does not contain a control group
    INDUCTION PHASE Cohort 1
    Primary Efficacy Endpoint:
    - The proportion of patients in clinical remission at Week 10.
    INDUCTION PHASE Cohort 2
    Cohort 2 is open label; therefore no formal analysis of efficacy endpoints
    will be conducted.
    All efficacy endpoints will be summarized and described without
    hypothesis testing.
    MAINTENANCE PHASE
    Primary Efficacy Endpoint:
    - The proportion of patients in clinical remission at 52 weeks
    Gli endpoint di efficacia saranno formalmente esaminati con test statistici condotti sui risultati di efficacia ottenuti dai pazienti randomizzati e trattati nella Cohort 1. La Cohort 2 è in aperto e non contiene un gruppo di controllo.
    FASE DI INDUZIONE COHORT 1:
    La percentuale di pazienti in remissione clinica alla Settimana 10.
    FASE DI INDUZIONE COHORT 2:
    La Coorte 2 è in aperto; pertanto non sarà condotta alcuna analisi formale degli endpoint di efficacia. Tutti gli endpoint di efficacia elencati sopra saranno riepilogati e descritti senza valutazione dell’ipotesi.
    FASE DI MANTENIMENTO:
    La percentuale di pazienti in remissione clinica a 52 settimane.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At 10 weeks (Induction Visit I4/Week 10)
    At 52 weeks (Maintenance Visit M5/Week 42)
    A 10 settimane (Induzione Visita I4/Settimana 10)
    A 52 settimane (Mantenimento Visita M5/Settimana 42)
    E.5.2Secondary end point(s)
    INDUCTION PHASE
    Key Secondary Efficacy Endpoints:
    - The proportion of patients with a clinical response at Week 10
    - The proportion of patients with endoscopic improvement at Week 10
    - The proportion of patients with mucosal healing at Week 10
    MAINTENANCE PHASE
    Key Secondary Efficacy Endpoints:
    - The proportion of patients with a clinical response at 52 weeks
    - The proportion of patients with endoscopic improvement at 52 weeks
    - The proportion of patients with durable clinical remission
    - The proportion of patients in clinical remission at 52 weeks in the
    subset of patients who were
    in remission at Week 10
    - The proportion of patients with corticosteroid-free remission
    - The proportion of patients with mucosal healing at 52 weeks
    OTHER ENDPOINTS
    Safety
    Pharmacokinetic and pharmacodynamic
    FASE DI INDUZIONE:
    Principali endpoint secondari di efficacia:
    - La percentuale di pazienti con una risposta clinica alla Settimana 10
    - La percentuale di pazienti con miglioramento endoscopica alla Settimana 10
    - La percentuale di pazienti con guarigione della mucosa alla settimana 10
    FASE DI MANTENIMENTO:
    Principali endpoint secondari di efficacia:
    - La percentuale di pazienti con una risposta clinica a 52 settimane
    - La percentuale di pazienti con un miglioramento endoscopico a 52 settimane
    - La percentuale di pazienti con remissione clinica durevole
    - La percentuale di pazienti in remissione clinica a 52 settimane nel sottogruppo di pazienti che erano
    in remissione alla settimana 10
    - La percentuale di pazienti con remissione senza corticosteroidi
    - La percentuale di pazienti con guarigione della mucosa a 52 settimane
    ALTRI ENDPOINTS
    Sicurezza
    Farmacocinetica e farmacodinamica
    E.5.2.1Timepoint(s) of evaluation of this end point
    At 10 weeks (Induction Visit I4/Week 10)
    At 52 weeks (Maintenance Visit M5/Week 42)
    From the list of Other efficacy endpoints during maintenance phase (not
    primary or secondary) some endpoints are evaluated at 28 weeks
    (Maintenance Visit M3/Week 18), 40 weeks (Maintenance Visit
    M3/Week 30) and 52 weeks (Maintenance Visit M3/Week 42).
    A 10 settimane (Induzione Visita I4 / Settimana 10)
    A 52 settimane (Mantenimento Visita M5 / Settimana 42)
    Dall'elenco di altri endpoint di efficacia durante la fase di mantenimento (non primaria o secondaria) alcuni endpoints saranno valutati a 28 settimane
    (Mantenimento Visita M3 / Settimana 18), 40 settimane (Mantenimento Visita M3 / Settimana 30) e 52 settimane (Maintenance Visit M3 / Settimana 42).
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    2 fasi. Induzione (Cohort1: Random PlaceboContr; Cohort2: OpenLabel); Mantenimento (PlaceboContr)
    2 phases. Induction (Cohort1: Random PlaceboContr; Cohort2:
    OpenLabel); Maintenance (PlaceboContr)
    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 trial4
    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 concerned13
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA93
    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
    Argentina
    Australia
    Austria
    Belarus
    Belgium
    Bulgaria
    Canada
    Czechia
    Georgia
    Germany
    Greece
    Hungary
    Israel
    Italy
    Korea, Republic of
    Latvia
    Moldova, Republic of
    Netherlands
    New Zealand
    Poland
    Romania
    Slovakia
    South Africa
    Ukraine
    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
    LVLS
    LVLS
    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 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: 873
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 27
    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 state43
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 427
    F.4.2.2In the whole clinical trial 900
    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)
    Patients may roll-over into an open-label extension study.
    I pazienti possono accedere ad una sperimentazione di estensione in aperto facoltativa.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-11-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-07-21
    P. End of Trial
    P.End of Trial StatusCompleted
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