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    Summary
    EudraCT Number:2017-000725-12
    Sponsor's Protocol Code Number:Cx601-0303
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Restarted
    Date on which this record was first entered in the EudraCT database:2017-06-06
    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 ConcernedSpain - AEMPS
    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.
    Estudio fase III, multicéntrico, internacional, aleatorizado, doble ciego, de grupos paralelos y controlado con placebo para evaluar la eficacia y la seguridad de células madre alogénicas expandidas derivadas del tejido adiposo (eASC) de adultos para el tratamiento de fístulas perianales complejas en pacientes con enfermedad de Crohn tras un periodo de 24 semanas y un periodo de seguimiento de 52 semanas. Estudio 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).
    Estudio de investigación clínica de un medicamento en investigación para el tratamiento de fístulas perianales en pacientes con enfermedad de Crohn (CD).
    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 number3491804 9264
    B.5.5Fax number3491804 9263
    B.5.6E-mailsergio.szyldergemajn@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 nameExpanded human allogenic mesenchymal adult stem cells extracted from adipose tissue
    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.3.8INN - Proposed INNTo be determined
    D.3.9.2Current sponsor codeAllogenic eASCs
    D.3.9.3Other descriptive nameExpanded human allogenic mesenchymal adult stem cells extracted from adipose tissue (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
    Enfermedad de Crohn perianal fistulizante
    E.1.1.1Medical condition in easily understood language
    Treatment for perianal fistulising Crohn´s disease
    Tratamiento para enfermedad de Crohn perianal fistulizante
    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.
    Evaluar la Remisión Combinada de la fístula o fístulas perianales, definida como la consideración clínica en la Semana 24 de haberse alcanzado el cierre de todos los orificios externos tratados que habían sido supurantes en el momento basal (esto es, en la visita de Selección), a pesar de su compresión digital ligera, y la ausencia de colecciones > 2 cm (en como mínimo dos dimensiones) con confirmación central mediante la lectura con enmascaramiento de la RM en la Semana 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.
    Evaluar la eficacia y la seguridad de Cx601, en comparación con placebo, sobre los parámetros clínicos y los criterios de valoración de tipo “tiempo hasta el evento” en las Semanas 24 y 52, y evaluar cuántos pacientes con Remisión Combinada en la Semana 24 presentan una remisión mantenida en la Semana 52 y cuántos han recaído hasta dicha Semana 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 Crohn’s Disease (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 internal openings and a maximum of 3 external openings, assessed by clinical examination and central reading of pelvic MRI. 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 less than 14 at Screening, AND
    2. a colonoscopy documenting the absence of ulcers larger than 0.5cm in the colonic mucosa: If colonoscopy data are not available within 6 months prior to Screening: a Simple Endoscopic Score for CD (SES-CD) less or equal to 6 with absence of rectal ulcers larger than 0.5cm must be documented in a colonoscopy performed at Screening before randomization. If colonoscopy data are available within 6 months prior to Screening, the following must be documented, otherwise a new colonoscopy (as above) will be mandatory: the absence of ulcers larger than 0.5cm 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 greater than 2.0 g/dl or an unexplained rising C-reactive protein (CRP), greater than 5.0 mg/l to a concentration above the referenced upper limit of normality (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 biologic therapy 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-α 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
    -TNFα antagonists
    - Anti-integrin
    - Anti-IL-12/23
    (7) Women of childbearing potential (WCBP) must have negative serum pregnancy test at screening (sensitive to 25 IU human chorionic gonadotropin [hCG]). Both WCBP or male patients participating in this study, with a WCBP as partner, must agree to use an adequate method of contraception during the entire duration of the study. An adequate method of contraception is defined as complete, non-periodic sexual abstinence, single-barrier method, adequate hormonal contraception (to have started at least 7 days prior to Screening visit), or an intra-uterine device (to have been in place for at least 2 months prior to Screening visit).
    (1)Firma del consentimiento informado
    (2)Pacientes de ambos sexos y edad >/=18 y </=75 años
    (3)Enfermedad de Crohn (CD) diagnosticada como mínimo 6 meses antes de la visita de Selección según los criterios clínicos, endoscópicos, histológicos y/o radiológicos habituales
    (4)Presencia de una o más fístulas perianales complejas con un máximo de 2 orificios internos y un máximo de 3 orificios externos, evaluadas mediante exploración clínica y lectura central de RM pélvica. La fístula o fístulas deberán haber sido supurantes durante como mínimo las 6 semanas anteriores a la visita de Selección. En este estudio no se permiten las fístulas subcutáneas simples activamente supurantes en la visita de Selección. Se define como fístula perianal compleja aquella fístula que cumple uno o más de los siguientes criterios:
    - Interesfinteriana alta, transesfinteriana alta, extraesfinteriana o supraesfinteriana
    - Presencia de >/= 2 orificios externos
    - Absceso o abscesos perianales asociados. Nota: En los abscesos mayores de 2 cm en como mínimo 2 dimensiones en la RM, para que el paciente sea elegible debe confirmarse que el cirujano los ha drenado adecuadamente durante el curetaje de preparación.
    (5)Enfermedad de Crohn clínicamente controlada, no activa o ligeramente activa, durante como mínimo los 6 meses anteriores a la visita de Selección, con:
    1.Puntuación de PRO-2 menor de 14 en la Selección, Y
    2.Colonoscopia demostrativa de la ausencia de úlceras mayores de 0,5 cm en la mucosa colónica: Si no se dispone de los datos de una colonoscopia practicada en los 6 meses anteriores a la Selección:Valor de la Simple Endoscopic Score for CD (SES-CD) menor de o igual a 6, con ausencia de úlceras rectales mayores de 0,5 cm, en una colonoscopia practicada en la Selección antes de la aleatorización.
    Si se dispone de los datos de una colonoscopia practicada en los 6 meses anteriores a la Selección, deberá documentarse lo siguiente [de no ser así, será imprescindible una nueva colonoscopia (con el resultado antes señalado)]:
    ausencia de úlceras mayores de 0,5 cm en la mucosa colónica Y mejoría o ausencia de deterioro del dolor abdominal y/o la diarrea, mantenidos durante una semana o más, desde la práctica de la última colonoscopia registrada en la historia clínica hasta la visita de Selección Y ausencia de disminución de la hemoglobina mayor de 2,0 g/dl o de aumento no explicado de la proteína C-reactiva (CRP), mayor de 5,0 mg/l, hasta una concentración por encima del límite superior de la normalidad (upper limit of normality, ULN) señalado (salvo si el aumento se debe a un proceso conocido distinto de enfermedad de Crohn luminal), desde la práctica de la última colonoscopia, en comparación con los resultados obtenidos durante la visita de Selección Y ausencia de inicio o de intensificación de pautas de tratamiento con corticosteroides, inmunosupresores o agentes biológicos desde la última endoscopia hasta la visita de Selección.
    (6)Pacientes con fístulas perianales previamente tratadas y que hayan mostrado una respuesta inadecuada (ausencia de cierre de parte de o de todos los tractos fistulosos, o nueva fístula durante el tratamiento de inducción) o pérdida de la respuesta (recidiva de la fístula durante el tratamiento de mantenimiento tras su cierre inicial) mientras estaban recibiendo un agente inmunosupresor o un antagonista del TNF-α o vedolizumab o ustekinumab, o con intolerancia documentada (presentación, en cualquier momento, de un nivel inaceptable de efectos secundarios relacionados con el tratamiento que hizo necesaria la suspensión del tratamiento) a cualquiera de estos tratamientos administrados a como mínimo las dosis recomendadas durante el siguiente periodo mínimo:
    -Inmunosupresores
    - Antagonistas del TNFα
    - Antiintegrina
    - Anti-IL-12/23
    (7)Las mujeres potencialmente fértiles (women of childbearing potential, WCBP) deben presentar en la selección un resultado negativo de una prueba de embarazo en suero (sensible a 25 UI de gonadotropina coriónica humana [hCG]). Tanto las mujeres potencialmente fértiles como los pacientes varones participantes en el estudio que tengan una pareja femenina potencialmente fértil deberán estar de acuerdo en utilizar un método anticonceptivo adecuado durante todo el estudio. Se define como método anticonceptivo adecuado lo siguiente: abstinencia sexual completa y no periódica, método de una sola barrera, anticoncepción hormonal adecuada (que deberá haber comenzado como mínimo 7 días antes de la visita Selección) o dispositivo intrauterino (colocado desde como mínimo 2 meses antes de la visita de Selección).
    E.4Principal exclusion criteria
    (1) Concomitant rectovaginal or rectovesical fistula(s)
    (2) Patient naïve to prior specific medical treatment for perianal complex fistula(s) including IS or anti-TNFs.
    (3) Presence of a perianal collection > 2 cm in at least two dimensions on the 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 that make impossible to follow the surgical protocol
    (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 Screening 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 upper limit of normality (ULN)
    b. Total bilirubin >1.5 ULN (unless predominantly non-conjugated due to documented history of Gilbert’s syndrome)
    c. AST/ALT >3.0 ULN
    d. Hemoglobin <10.0 g/dL
    e. Platelets <75.0 x109/L
    f. Albuminemia < 3.0 g/dL
    (9) Suspected or documented infectious enterocolitis within two 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 (Dulbecco Modified Eagle’s Medium); bovin serum; local anaesthetics or gadolinium (MRI contrast)
    (16) Contraindication to MRI scan (e.g., due to the presence of pacemakers, hip replacements or severe claustrophobia)
    (17) Major surgery or 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 for CD or the perianal fistula(s) 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) Surgery of one or more segments of the colon or terminal ileum within 3 months prior to Screening visit
    (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, or for whom such major surgery is foreseen in this region in the 24 weeks following treatment administration at the time of screening
    (24) Contraindication to the anaesthetic procedure
    (1)Fístula o fístulas rectovaginales o rectovesicales concomitantes
    (2)Paciente que no ha recibido previamente un tratamiento médico específico para la fístula o fístulas perianales complejas, tal como IS o anti-TNF.
    (3)Presencia de una colección perianal > 2 cm en como mínimo dos dimensiones en la lectura central de la RM en la visita de Selección que, en opinión del cirujano, no se ha drenado adecuadamente durante el procedimiento de preparación (semana -3 a día 0)
    (4)Estenosis rectal y/o anal severa que imposibilita seguir el protocolo quirúrgico
    (5)Paciente con estomas derivativos
    (6)Infección activa no controlada que precisa antibióticos parenterales
    (7)Paciente en tratamiento con corticosteroides sistémicos o rectales por enfermedad de Crohn en las 2 últimas semanas antes de la visita de Selección
    (8)Paciente con alteración mayor de cualquiera de las siguientes pruebas de laboratorio o de riesgo para el procedimiento quirúrgico:
    a.Creatinina sérica >1,5 veces el límite superior de la normalidad
    b.Bilirrubina total >1,5 veces el límite superior de la normalidad (salvo si se trata fundamentalmente de la bilirrubina no conjugada como consecuencia de historia documentada de síndrome de Gilbert)
    c.AST/ALT >3,0 veces el límite superior de la normalidad
    d.Hemoglobina <10,0 g/dL
    e.Plaquetas <75,0 x109/L
    f.Albuminemia < 3,0 g/dL
    (9)Sospecha o documentación de enterocolitis infecciosa en el plazo de las 2 semanas anteriores a la visita de Selección
    (10)Cualquier proceso maligno invasivo diagnosticado en el plazo de los últimos 5 años anteriores a la visita de Selección. Pueden participar los pacientes con carcinoma cutáneo de células basales plenamente resecado situado fuera de la región perianal
    (11)Presencia actual o historia reciente (en el plazo de los 6 meses anteriores a la visita de Selección) de enfermedad severa, progresiva y/o no controlada de carácter hepático, hematológico, gastrointestinal (distinta de la enfermedad de Crohn), renal endocrino, pulmonar, cardiaco, neurológico o psiquiátrico que pueda suponer un aumento del riesgo para el paciente como consecuencia de su participación en el estudio y/o su incumplimiento con los procedimientos del estudio
    (12)Paciente con colangitis esclerosante primaria
    (13)Paciente con hepatopatía activa crónica de cualquier origen, incluida la cirrosis, y paciente con positividad persistente del antígeno de superficie del virus de la hepatitis B (HBsAg) y de la reacción en cadena de la polimerasa (PCR) cuantitativa del virus de la hepatitis B, o positividad de la serología para el virus de la hepatitis C y de la PCR cuantitativa para el virus de hepatitis C en el plazo de los 6 meses anteriores a la Selección.
    (14)Inmunodeficiencias congénitas o adquiridas, incluidos los pacientes que se sabe que son portadores del virus de la inmunodeficiencia humana
    (15)Alergia o hipersensibilidad conocida a la penicilina o a los aminoglucósidos; al DMEM (Dulbecco Modified Eagle’s Medium); al suero bovino; a los anestésicos locales o al gadolinio (agente de contraste para la RM)
    (16)Contraindicación para la RM (por ejemplo, presencia de marcapasos, prótesis de cadera o claustrofobia severa)
    (17)Cirugía mayor o traumatismo importante en el plazo de los 6 meses anteriores a la visita de Selección
    (18)Mujeres embarazadas o que están amamantando
    (19)Pacientes que no desean o no pueden cumplir con los procedimientos del estudio
    (20)Pacientes que están recibiendo actualmente o que han recibido un fármaco en fase de experimentación para la enfermedad de Crohn o para las fístulas perianales en el plazo de los 3 meses anteriores a la visita de Selección
    (21)Pacientes tratados previamente con Cx601 u otro tratamiento de células madre alogénicas
    (22)Cirugía de uno o más segmentos de colon o de íleon terminal en el plazo de los 3 meses anteriores a la visita de Selección
    (23)Pacientes que han sido sometidos a cirugía perianal local distinta del drenaje fistular en el plazo de los 6 meses anteriores a la visita de Selección o que, en el momento de su inclusión en el estudio, pudieran precisar cirugía en la región perianal por razones distintas de las fístulas, o en los que, en el momento de la Selección fuera previsible una cirugía mayor de esta región en el plazo de las 24 semanas siguientes a la administración del tratamiento
    (24)Contraindicación al procedimiento anestésico
    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.
    El Criterio de valoración principal en la Semana 24 se define como la Remisión Combinada de la fístula o fístulas perianales, definida como la consideración clínica en la Semana 24 de haberse alcanzado el cierre de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, y la ausencia de colecciones > 2 cm (en como mínimo dos dimensiones) con confirmación central mediante la lectura con enmascaramiento de la RM en la Semana 24.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at week 24
    Semana 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.
    Eficacia en la Semana 24
    -CRITERIO CLAVE: Remisión Clínica en la Semana 24, definida como el cierre de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, en su evaluación clínica en la Semana 24.
    -CRITERIO CLAVE: Respuesta en la Semana 24, definida como el cierre de como mínimo el 50% de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, en su evaluación clínica en la Semana 24.
    -Tiempo hasta la Remisión Clínica antes de finalizada la Semana 24 (tiempo desde el comienzo del tratamiento hasta la primera visita con cierre de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, en su evaluación clínica).
    -Tiempo hasta la Respuesta antes de finalizada la Semana 24 (tiempo desde el comienzo del tratamiento hasta la primera visita con cierre de como mínimo el 50% de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, en su evaluación clínica).
    Eficacia en la Semana 52
    -Remisión Combinada de la fístula o fístulas perianales, definida como la consideración clínica en la Semana 52 de haberse alcanzado el cierre de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, y la ausencia de colecciones > 2 cm (en como mínimo dos dimensiones) con confirmación central mediante la lectura con enmascaramiento de la RM en la Semana 52.
    -Remisión Clínica, definida como el cierre de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, en su evaluación clínica en la Semana 52.
    -Respuesta, definida como el cierre de como mínimo el 50% de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, en su evaluación clínica en la Semana 52.
    -Tiempo hasta la Remisión Clínica antes de finalizada la Semana 52 (tiempo desde el comienzo del tratamiento hasta la primera visita con cierre de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, en su evaluación clínica).
    -Tiempo hasta la Respuesta antes de finalizada la Semana 52 (tiempo desde el comienzo del tratamiento hasta la primera visita con cierre de como mínimo el 50% de todos los orificios externos tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera, en su evaluación clínica).
    - Recidiva antes de finalizada la Semana 52, definida, en los pacientes con Remisión Combinada antes de finalizada la Semana 24, como la reapertura de cualquier orificio externo tratado con supuración activa en su evaluación clínica o presencia de una o más colecciones >2 cm (en como mínimo 2 dimensiones) de la fístula o fístulas perianales tratadas, con confirmación por la RM central con enmascaramiento antes de finalizada la Semana 52.
    E.5.2.1Timepoint(s) of evaluation of this end point
    at 24 and 52 weeks after the treatment
    Semana 24 y 52 después del tratamiento
    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 concerned15
    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 No
    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
    Czech Republic
    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
    Último Paciente Última Visita
    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 state29
    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.
    No hay planes previstos
    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 Decision2017-07-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-07-26
    P. End of Trial
    P.End of Trial StatusRestarted
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