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    Summary
    EudraCT Number:2017-000725-12
    Sponsor's Protocol Code Number:Cx601-0303
    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:2020-11-09
    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 number2017-000725-12
    A.3Full title of the trial
    A phase III, randomized, double blind, parallel group, placebo controlled, international, multicentre study to assess efficacy and safety of Cx601, adult allogeneic expanded adipose-derived stem cells (eASC), for the treatment of complex perianal fistula(s) in patients with Crohn’s disease over a period of 24 weeks and a follow-up period up to 52 weeks. ADMIRE-CD II study.
    Studio di fase 3, internazionale, multicentrico, randomizzato, in doppio cieco, a gruppi paralleli, controllato con placebo sulla sicurezza e sull’efficacia di Cx601, cellule staminali adulte derivate da tessuto adiposo, allogeniche, espanse (eASC), nel trattamento di fistole perianali complesse in pazienti con malattia di Crohn per un periodo di 24 settimane con un follow-up fino a 52 settimane. Studio ADMIRE-CD II.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical research study of an investigational new drug to treat perianal fistulas in patients with Crohn’s disease (CD).
    Studio di ricerca clinica per un prodotto medicinale nel trattamento di fistole perianali in pazienti con malattia di Crohn.
    A.3.2Name or abbreviated title of the trial where available
    -
    -
    A.4.1Sponsor's protocol code numberCx601-0303
    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 SponsorTIGENIX S.A.U
    B.1.3.4CountrySpain
    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 supportTiGenix S.A.U.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTiGenix, S.A.U.
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street AddressC/ Marconi 1. Parque Tecnológico de Madrid
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28760
    B.5.3.4CountrySpain
    B.5.4Telephone number0034918049264
    B.5.5Fax number0034918049263
    B.5.6E-mailimmaculada.gilberte@tigenix.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/09/667
    D.3 Description of the IMP
    D.3.1Product nameAllogenic eASCs 5 million cells/ml suspension for injection CX601
    D.3.2Product code [Cx601]
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntralesional use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeAllogenic eASCs
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5000000
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntralesional use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Perianal fistulising Crohn´s disease
    Fistole perianali del morbo di Crohn
    E.1.1.1Medical condition in easily understood language
    Treatment for perianal fistulising Crohn´s disease
    Trattamento per le fistole perianali del morbo di Crohn
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10002156
    E.1.2Term Anal fistula
    E.1.2System Organ Class 10017947 - Gastrointestinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the Combined Remission of complex perianal fistula(s), defined as the clinical assessment at Week 24 of closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collections >2 cm (in at least 2 dimensions) confirmed by blinded central MRI assessment at Week 24.
    Valutare la remissione combinata delle fistole perianali complesse, definita come valutazione clinica alla settimana 24 di chiusura di tutte le ferite esterne trattate che sono state drenate alla base nonostante la compressione con le dita, e assenza di fistole > 2 cm (in almeno 2 dimensioni) confermata da una valutazione MRI centrale blinded alla settimana 24.
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy and safety of Cx601 as compared to placebo in clinical parameters and time-related endpoints at Weeks 24 and 52, and to evaluate how many patients with Combined Remission at Week 24 have sustained remission at Week 52 and those who relapse by Week 52.
    Valutare la sicurezza e l'efficacia di Cx601 rispetto a placebo nei parametri clinici e negli endpoint correlati al tempo alla settimana 24 e 52, e valutare qualti pazienti con la remissione combinata alla settimana 24 hanno sostenuto una remissione alla settimana 52 e quelli che hanno la ricatuta alla settimana 52.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    (1) Signed informed consent
    (2) Patients of either gender >= 18 years and <=75 years of age
    (3) Patients with CD diagnosed at least 6 months prior to Screening visit in accordance with accepted clinical, endoscopic, histological and/or radiological criteria
    (4) Presence of complex perianal fistula(s) with a maximum of 2 internalopenings and a maximum of 3 external openings based on assessment; acentral reading of a locally performed contrast enhanced (gadolinium) pelvic MRI will be perfomed to confirm location of the fistula and potential associated perianal abscess(es). Fistula(s) must have been draining for at least 6 weeks prior to Screening visit. Actively draining simple subcutaneous fistula(s), at the time of Screening visit, are not allowed in this study. A complex perianal fistula is defined as a fistula that meets one or more of the following criteria :• High inter-sphincteric, high trans-sphincteric, extra-sphincteric or supra-sphincteric• Presence of >= 2 external openings• Associated perianal abscess(es). Note: Abscesses that are larger than 2 cm in at least 2 dimensions on MRI must be confirmed to have been drained adequately by the surgeon during the preparation curettage in order to be eligible.
    (5) Clinically controlled, non active or mildly active CD, during the last six months prior to Screening visit with:1. a PRO-2 score < 14 at Screening, AND2. a colonoscopy documenting the absence of ulcers larger than 0.5 cm in the colonic mucosa: If colonoscopy data are not available within 6 months prior to Screening: a SES-CD <= 6 with absence of rectal ulcers larger than 0.5 cm must be documented in a colonoscopy performed at Screening before randomization. If colonoscopy data are available within6 months prior to Screening, the following must be documented, otherwise a new colonoscopy (as above) will be mandatory: the absence of ulcers larger than 0.5 cm in the colonic mucosa AND the improvement or no worsening in abdominal pain and/or in the diarrhea, sustained for one week or more, since the last colonoscopy was performed in the clinical records until Screening visit AND no hemoglobin decrease > 2.0 g/dL or an unexplained rising C-reactive protein (CRP), greater than 5.0 mg/L to a concentration above the referenced ULN (unless the rise is due to a known process other than luminal Crohn's Disease), since the last colonoscopy was performed as compared to results during the Screening visit AND no initiation or intensification of treatment with corticosteroids, immunosuppressants or mAbs dose regimen since the last endoscopy up to Screening visit.
    (6) Patients whose perianal fistulas were previously treated and have shown an inadequate response (absence of closure of part or all fistula tracts, or new fistula during induction treatment) or a loss of response (fistula relapse during maintenance treatment after initial fistula closure) while they were receiving either an immunosuppressive agent or TNF-a antagonist or vedolizumab or ustekinumab, or having documented intolerance (occurrence, at any time, of an unacceptable level of treatment-related side effects that makes necessary treatment discontinuation) to any of these treatments administered at least at approved or recommended doses during the minimum period mentioned:-Immunosuppressive agents-TNFa antagonists- Anti-integrin- Anti-IL-12/23
    For further inclusione criteria, please refer to the Protocol.
    (1)Firma del consenso informato
    (2)Pazienti, di ambo i sessi, di età compresa tra >= 18 e <= 75 anni
    (3)Diagnosi di MC da almeno 6 mesi prima della Visita di screening conformemente ai criteri clinici, endoscopici, istologici e/o radiologici accettati
    (4)Presenza di una o più fistole perianali complesse con massimo 2 aperture interne e massimo 3 aperture esterne, valutate mediante esame clinico e con refertazione centrale di una RMI della pelvi effettuata localmente con contrasto (gadolinio) per confermare la posizione delle fistole ed il potenziale ascesso(i) anale associato. Le fistole devono essere drenanti da almeno 6 settimane prima della Visita di screening. In questo studio non sono ammessi pazienti con fistole sottocutanee semplici attivamente drenanti al momento della Visita di screening. Si definisce fistola perianale complessa una fistola che risponde a uno o più dei seguenti criteri:
    •localizzazione intersfinterica alta, transfinterica alta, extrasfinterica o soprasfinterica
    •presenza di >= 2 aperture esterne
    •ascesso/i perianale/i associato/i. Nota: per risultare idonei, gli ascessi > 2 cm in almeno 2 dimensioni alla RMI devono essere stati adeguatamente drenati dal chirurgo durante il curettage di preparazione.
    (5)MC inattiva o lievemente attiva, clinicamente controllata, negli ultimi sei mesi prima della Visita di screening con:
    1.punteggio PRO-2 inferiore a 14 allo Screening, E
    2.colonscopia che documenta l’assenza di ulcere di dimensioni superiori a 0,5 cm nella mucosa colica:
    • se non sono disponibili i risultati di una colonscopia eseguita nei 6 mesi precedenti lo Screening:
    •il punteggio SES-CD (Simple Endoscopic Score for CD) deve risultare inferiore o uguale a 6 con assenza di ulcere rettali di dimensioni superiori a 0,5 cm, come documentato da una colonscopia eseguita allo Screening prima della randomizzazione
    •se sono disponibili i risultati di una colonscopia eseguita nei 6 mesi precedenti lo Screening, occorre documentare quanto segue. In caso contrario, è obbligatoria una nuova colonscopia (come sopra):
    •assenza di ulcere di dimensioni superiori a 0,5 cm nella mucosa colica E
    •miglioramento o assenza di peggioramento del dolore addominale e/o della diarrea per una settimana o più dall’ultima colonscopia effettuata, come risulta dalle cartelle cliniche, fino alla Visita di screening E
    •nessuna riduzione dell’emoglobina superiore a 2,0 g/dl né aumento inspiegato dei livelli di proteina C reattiva (PCR) superiore a 5,0 mg/l a una concentrazione al di sopra del limite superiore della norma (ULN) preso a riferimento (salvo l’aumento sia dovuto a un processo noto, diverso dalla malattia di Crohn luminale, dall’ultima colonscopia effettuata rispetto ai risultati ottenuti durante la Visita di screening E
    •nessun trattamento con corticosteroidi, immunosoppressori o anticorpi monoclonali avviato o intensificato dall’ultima endoscopia fino alla Visita di screening.
    (6)Pazienti con fistole perianali precedentemente trattate con i seguenti esiti: risposta inadeguata (assenza di chiusura di parte del tratto interessato dalla fistola o dell’intero tratto, o sviluppo di una nuova fistola durante il trattamento di induzione), perdita di risposta (recidiva di fistola durante il trattamento di mantenimento dopo l’iniziale chiusura della fistola) durante il trattamento con un agente immunosoppressore, un antagonista del TNF-a, vedolizumab o ustekinumab, oppure intolleranza documentata (insorgenza, in qualsiasi momento, di un livello inaccettabile di effetti indesiderati correlati al trattamento che ne richiede l’interruzione) a uno qualsiasi di questi trattamenti somministrati almeno a dosi approvate o raccomandate durante il periodo minimo indicato:
    •agenti immunosoppressori
    •antagonisti del TNFa:
    •anti-integrina
    Per ulteriori criteri di inclusione, si prega di fare riferimento al Protocollo.
    E.4Principal exclusion criteria
    (1) Concomitant rectovaginal or rectovesical fistula(s).
    (2) Patient naïve to prior specific medical treatment for complex perianalfistula(s) including IS or anti-TNFs.
    (3) Presence of a perianal collection >2 cm in at least two dimensions onthe central reading MRI at Screening visit that was not adequately drained as confirmed by the surgeon during the preparation procedure
    (week -3 to day 0).
    (4) Severe rectal and/or anal stenosis and/or severe proctitis (defined as the presence of large [>0.5 cm] ulcers in the rectum) that make impossible to follow the Surgery Procedure Manual.
    (5) Patient with diverting stomas.
    (6) Active, uncontrolled infection requiring parenteral antibiotics.
    (7) Patient with ongoing systemic or rectal steroids for CD in the last 2 weeks prior to Preparation visit.(8) Patients with major alteration on any of the following laboratory tests or increased risk for the surgical procedure:a. Serum creatinine levels >1.5 times the ULNb. Total bilirubin >1.5 times the ULN (unless predominantly non-conjugated due to documented history of Gilbert's syndrome)c. AST/ALT >3.0 times the ULNd. Hemoglobin <10.0 g/dLe. Platelets <75.0 x 109/Lf. Albuminemia <3.0 g/dL
    (9) Suspected or documented infectious enterocolitis within 2 weeks prior to Screening visit.(10) Any prior invasive malignancy diagnosed within the last 5 years prior to Screening visit. Patients with basal-cell carcinoma of the skin completely resected outside the perineal region can be included.
    (11) Current or recent (within 6 months prior to the Screening visit) history of severe, progressive, and/or uncontrolled hepatic, haematological, gastrointestinal (other than CD), renal, endocrine, pulmonary, cardiac, neurological or psychiatric disease that may result in patients increased risk from study participation and/or lack of compliance with study procedures
    (12) Patients with primary sclerosing cholangitis
    (13) Patients with known chronically active hepatopathy of any origin, including cirrhosis and patients with persistent positive HBV surface antigen (HBsAg) and quantitative HBV polymerase chain reaction (PCR), or positive serology for HCV and quantitative HCV PCR within 6 months prior to Screening.
    (14) Congenital or acquired immunodeficiencies, including patients known to be HIV carriers
    (15) Known allergies or hypersensivity to penicillin or aminoglycosides; DMEM; bovine serum; local anaesthetics or gadolinium (MRI contrast).
    (16) Contraindication to MRI scan (e.g., due to the presence of pacemaker, hip replacement or severe claustrophobia).
    (17) Severe trauma within 6 months prior to Screening visit.
    (18) Pregnant or breastfeeding women.
    (19) Patients who do not wish to or cannot comply with study procedures
    .(20) Patients currently receiving, or having received any investigational drug within 3 months prior to Screening visit.
    (21) Patients previously treated with Cx601 or other allogeneic stem-cell therapy cannot be enrolled into this clinical study.
    (22) Any major surgery of the GI tract (including one or more segments of the colon or terminal ileum) within 6 months prior to screening or anyminor surgery of the GI tract within 3 months prior to screening.
    (23) Patients who had local perianal surgery other than drainage for the fistula within 6 months prior to the Screening visit, or those who may need surgery in the perianal region for reasons other than fistulas at the time of inclusion in the study.
    (24) Contraindication to the anaesthetic procedure.
    (1)Presenza di una o più fistole retto-vaginali o retto-vescicali concomitanti
    (2)Pazienti non precedentemente sottoposti a terapie mediche specifiche per le fistole perianali complesse inclusi IS o anti-TNF
    (3)Presenza di una raccolta perianale > 2 cm in almeno 2 dimensioni alla RMI refertata centralmente alla Visita di screening, che non è stata adeguatamente drenata, come confermato dal chirurgo durante la procedura di preparazione (dalla Settimana -3 al Giorno 0)
    (4)Grave stenosi rettale e/o anale e/o proctite grave (definita dalla presenza di un’ulcera larga [> o uguale a 0,5 cm] nel retto) che rende impossibile attenersi al Manuale di protocollo chirurgico.
    (5)Pazienti con stomie derivative
    (6)Infezione attiva, non controllata, che richiede antibiotici parenterali
    (7)Assunzione continuativa di steroidi per via sistemica o rettale per la MC nelle ultime 2 settimane precedenti la Visita di Preparazione.
    (8)Alterazione significativa dei valori di uno dei seguenti esami di laboratorio o aumentato rischio per la procedura chirurgica:
    a.creatinina sierica > 1,5 volte il limite superiore della norma (ULN)
    b.bilirubina totale > 1,5 volte il ULN (salvo prevalentemente non coniugata per storia documentata di sindrome di Gilbert)
    c.AST/ALT > 3,0 volte il ULN
    d.emoglobina < 10,0 g/dL
    e.piastrine < 75,0 x109/L
    f.albuminemia < 3,0 g/dL
    (9)Enterocolite infettiva sospetta o documentata nelle due settimane precedenti la Visita di screening
    (10) Precedente neoplasia maligna invasiva diagnosticata negli ultimi 5 anni prima della Visita di Screening. Possono essere inclusi nello studio pazienti con carcinoma cutaneo baso-cellulare sito al di fuori della regione perineale completamente asportato
    (11) Storia, corrente o recente (nei 6 mesi precedenti la Visita di screening), di grave malattia epatica, ematologica, gastrointestinale (diversa dalla MC), renale, endocrina, polmonare, cardiaca, neurologica o psichiatrica, progressiva e/o non controllata, che può comportare un aumentato rischio per i pazienti a causa della partecipazione allo studio e/o una mancanza di compliance con le procedure di studio
    (12) Pazienti con colangite sclerosante primitiva
    (13) Pazienti con epatopatia nota, cronicamente attiva, di qualunque origine, inclusa cirrosi, e pazienti con positività persistente all’antigene di superficie HBV (HBsAg) e alla reazione a catena della polimerasi (PCR) quantitativa per HBV o agli esami sierologici per HCV e alla PCR quantitativa per HCV nei 6 mesi precedenti lo Screening
    (14) Immunodeficienze congenite o acquisite, inclusi pazienti portatori di HIV
    (15) Ipersensibilità o allergie note a penicillina o aminoglicosidi, DMEM (Dulbecco Modified Eagle’s Medium), siero bovino, anestetici locali o gadolinio (contrasto per la RMI)
    (16) Controindicazione alla scansione RMI (p. es. a causa della presenza di pacemaker, di sostituzioni d’anca o di grave claustrofobia)
    (17) Grave trauma nei 6 mesi precedenti la Visita di Screening
    (18) Donne in gravidanza o allattamento
    (19) Pazienti che non desiderano o non in grado di attenersi alle procedure di studio
    (20) Pazienti in trattamento corrente con un farmaco sperimentale per la MC nei 3 mesi precedenti la Visita di Screening
    (21) I pazienti precedentemente trattati con Cx601 o altra terapia a base di staminali allogeniche non possono essere arruolati in questo studio clinico
    (22) Intervento chirurgico importante nel tratto GI (inclusi uno o più segmenti del colon o dell’ileo terminale) nei 6 mesi precedenti la Visita di Screening o intervento chirurgico minore nel tratto GI nei 3 mesi precedenti la Visita di Screening
    (23) Pazienti sottoposti a chirurgia perianale locale, diversa dal drenaggio per la fistola, nei 6 mesi precedenti la Visita di screening, o pazienti che al momento dell’inclusione nello studio potrebbero aver bisogno di tale intervento per motivi diversi dalle fistole
    (24) Controindicazione alla procedura anestetica
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint at Week 24 is defined to be the Combined Remission of complex perianal fistula(s), defined as the clinical assessment by Week 24 of closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collection(s) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment by Week 24.
    Remissione combinata di fistole perianali, definita come valutazione clinica alla Settimana 24 della chiusura di tutte le aperture esterne trattate drenanti al basale (Visita di Screening), nonostante una leggera compressione a mano libera, e assenza di raccolte > 2 cm (in almeno 2 dimensioni), come confermato dalla valutazione centrale in cieco della RMI alla Settimana 24.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At week 24
    Alla settimana 24
    E.5.2Secondary end point(s)
    Efficacy at Week 24
    • KEY: Clinical Remission at Week 24, defined as closure of all treated external openings that were draining at baseline despite gentle finger
    compression, as clinically assessed at Week 24.
    • KEY: Response at Week 24, defined as closure of at least 50% of all treated external openings that were draining at baseline, despite gentle
    finger compression, as clinically assessed at Week 24.
    • Time to Clinical Remission by Week 24 (time from treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed).
    • Time to Response by Week 24 (time from treatment start to first visit with closure of at least 50% of all treated external openings that were
    draining at baseline, despite gentle finger compression, as clinically assessed).
    Efficacy at Week 52
    • Combined Remission of perianal fistula(s), defined as the clinical assessment at Week 52 of closure of all treated external openings that
    were draining at baseline, despite gentle finger compression, and absence of collection(s) >2 cm (in at least 2 dimensions) confirmed by
    blinded central MRI assessment at Week 52.
    • Clinical Remission defined as closure of all treated external openings that were draining at baseline, despite gentle finger compression, as
    clinically assessed at Week 52.
    • Response defined as closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed at Week 52.
    • Time to Clinical Remission by Week 52 (time from treatment start to first visit with closure of all treated external openings that were draining
    at baseline, despite gentle finger compression, as clinically assessed).
    • Time to Response by Week 52 (time from treatment start to first visit with closure of at least 50% of all treated external openings that were
    draining at baseline despite gentle finger compression, as clinically assessed).
    • Relapse by Week 52 defined in patients with Combined Remission by Week 24, as reopening of any of the treated external openings with
    active drainage as clinically assessed or the presence of collection(s) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment by Week 52.
    Efficacia alla Settimana 24
    •PRINCIPALE: Remissione clinica alla Settimana 24, definita come chiusura di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, come clinicamente valutato alla Settimana 24.
    •PRINCIPALE: Risposta alla Settimana 24, definita come chiusura di almeno il 50% di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, come clinicamente valutato alla Settimana 24.
    •Tempo alla remissione clinica entro la Settimana 24 (tempo dall’inizio del trattamento alla prima visita con chiusura di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, come risulta dalla valutazione clinica).
    •Tempo alla risposta entro la Settimana 24 (tempo dall’inizio del trattamento alla prima visita con chiusura di almeno il 50% di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, come risulta dalla valutazione clinica).
    Efficacia alla Settimana 52
    •Remissione combinata delle fistole perianali, definita come valutazione clinica alla Settimana 52 della chiusura di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, e assenza di raccolte > 2 cm (in almeno 2 dimensioni), come confermato dalla valutazione centrale in cieco della RMI alla Settimana 52.
    •Remissione clinica, definita come chiusura di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, come risulta dalla valutazione
    clinica alla Settimana 52.
    •Risposta, definita come chiusura di almeno il 50% di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, come risulta dalla valutazione clinica alla Settimana 52.
    •Tempo alla remissione clinica entro la Settimana 52 (tempo dall’inizio del trattamento alla prima visita con chiusura di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, come risulta dalla valutazione clinica).
    •Tempo alla risposta entro la Settimana 52 (tempo dall’inizio del trattamento alla prima visita con chiusura di almeno il 50% di tutte le aperture esterne trattate drenanti al basale, nonostante una leggera compressione a mano libera, come risulta dalla valutazione clinica).
    •Recidiva entro la Settimana 52, definita, nei pazienti con remissione combinata entro la Settimana 24, come riapertura di una qualsiasi delle aperture esterne trattate con drenaggio attivo alla valutazione clinica, o presenza di raccolte > 2 cm (in almeno 2 dimensioni) delle fistole perianali trattate, come confermato dalla valutazione centrale in cieco della RMI entro la Settimana 52.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At 24 and 52 weeks after the treatment
    Alla settimana 24 e 52 dopo il trattamento
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic 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 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 concerned14
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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
    Belgium
    Canada
    Czechia
    France
    Hungary
    Israel
    Italy
    Poland
    Spain
    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
    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 months10
    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 months10
    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: 260
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 66
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 326
    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)
    No plans are foreseen.
    Non sono previsti piani
    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 Decision2017-10-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-08
    P. End of Trial
    P.End of Trial StatusOngoing
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