Clinical Trials Register

Summary
EudraCT Number:	2018-002925-47
Sponsor's Protocol Code Number:	GIS-2018-BioIBD
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-11-16
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2018-002925-47

A.3

Full title of the trial

Identification of predictive biomarkers for response to biologic therapies in inflammatory bowel disease by proteomic and mass cytometry approaches

IDENTIFICACIÓN DE BIOMARCADORES DE RESPUESTA AL TRATAMIENTO CON FÁRMACOS BIOLÓGICOS EN LA ENFERMEDAD INFLAMATORIA INTESTINAL

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

prediction of response to therapy in inflammatory bowel disease

Predicción de respuesta al tratamiento en la enfermedad inflamatoria intestinal

A.4.1

Sponsor's protocol code number

GIS-2018-BioIBD

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fundación de Investigación Biomédica del Hospital Universitario de La Princesa
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Instituto de Salud Carlos III
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	fundación de Investigación Biomédica Hospital Universitario de La Princesa
B.5.2	Functional name of contact point	Ana Garre
B.5.3	Address:
B.5.3.1	Street Address	C/ Diego de León, 62, 3ª planta
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28006
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34913093911
B.5.5	Fax number	+34915204013
B.5.6	E-mail	anagarre.laprincesa@gmail.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Adalimumab
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.4	EV Substance Code	SUB20016
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Infliximab
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLIXIMAB
D.3.9.1	CAS number	170277-31-3
D.3.9.4	EV Substance Code	SUB02681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Golimumab
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GOLIMUMAB
D.3.9.1	CAS number	476181-74-5
D.3.9.4	EV Substance Code	SUB25638
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Ustekinumab
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	USTEKINUMAB
D.3.9.1	CAS number	815610-63-0
D.3.9.3	Other descriptive name	USTEKINUMAB
D.3.9.4	EV Substance Code	SUB27761
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	90
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vedolizumab
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VEDOLIZUMAB
D.3.9.1	CAS number	943609-66-3
D.3.9.3	Other descriptive name	VEDOLIZUMAB
D.3.9.4	EV Substance Code	SUB30452
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Inflammatory bowel disease

Enfermedad inflamatoria intestinal

E.1.1.1

Medical condition in easily understood language

Corhn´s disease and ulcerative colitis

Enfermedad de Crohn y colitis ulcerosa

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011401
E.1.2	Term	Crohn's disease
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

identify novel biomarkers of clinical response to the different available therapies in IBD, including Crohn´s disease (CD) and ulcerative colitis (UC).

Identificar biomarcadores en sangre y en tejido intestinal mediante un abordaje de citometría de masas y proteómica que permitan predecir la respuesta a cada uno de los tratamientos biológicos aprobados actualmente (anti-TNFα, vedolizumab y ustekinumab) en pacientes con EII.

E.2.2

Secondary objectives of the trial

1. To determine the presence and severity of endoscopic inflammation by non-invasive approaches (in the absence of a ilecolonoscopy), before starting treatment and on the follow-up period, with the aim of monitoring treatment response.
2. To identify the immune cell subsets and signalling pathways specifically modulated by each of the biologic treatments in responding patients, both in CD and UC.
3. To identify similarities and differences on the mechanism of action of a given drug in both UC and CD.

1. -Estimar la presencia y gravedad de las lesiones endoscópicas de los pacientes con EII de manera no invasiva (esto es, sin precisar endoscopia); tanto al inicio del tratamiento biológico como tras haberlo recibido (en este último caso con el objetivo de monitorizar la respuesta al tratamiento).
2. -Identificar las sub-poblaciones celulares del sistema inmune específicamente moduladas por cada uno de los distintos fármacos biológicos en los pacientes respondedores, tanto con enfermedad de Crohn (EC) como con colitis ulcerosa (CU).
3.-Identificar similitudes y diferencias en el mecanismo de actuación (a nivel proteómico y celular) de un mismo tratamiento biológico en pacientes con EC y CU.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Group 1: Patients with IBD

- Over 18 years.
- Diagnosis of IBD according to the criteria of the European Crohns and Colitis Organization (ECCO).
- Have indication of treatment with a biologic drug.
- Be the first received biologic drug with a given mechanism of action (anti-TNFα, anti-α4β7 or anti-p40).
- Have endoscopic activity of IBD within 1 month of starting the biologic treatment (see definitions section: SES-CD ≥ 3 in CD and endoscopic sub-index of May ≥ 2 in UC).
- In the case of CD, receive the biologic treatment by luminal activity (not perianal).
- Previous treatments (including corticosteroids and immunosuppressants) are allowed provided that they have been stable for the last 3 months prior to beginning treatment with biologics and that they are maintained at a stable dose for the duration of the study.

Group 2: patients without IBD

- Patients not diagnosed with IBD, or other inflammatory, allergic, malignant or autoimmune diseases, where a ilecolonoscopy is performed due to the normal clinical practice.

GRUPO 1: PACIENTES CON EII

- Mayores de 18 años.
- Diagnóstico de EII según los criterios de la European Crohn´s and Colitis Organisation (ECCO).
- Tener indicación de tratamiento con un fármaco biológico.
- Ser el primer fármaco biológico que recibe con un determinado mecanismo de acción (anti-TNFα, anti-α4β7 o anti-p40).
- Tener actividad endoscópica de la EII en el momento (o como máximo 1 mes antes) de iniciar el tratamiento biológico (véase apartado de definiciones: SES-CD ≥ 3 en EC y subíndice endoscópico de Mayo ≥ 2 en CU).
- En el caso de la EC, recibir el tratamiento biológico por actividad luminal (no perianal).
- Se permiten los tratamientos previos (incluyendo corticoides e inmunosupresores) siempre que se hayan mantenido estables durante los últimos 3 meses previo a iniciar el tratamiento con biológicos y que se mantengan a su vez a dosis estable durante la duración del estudio.

GRUPO 2: PACIENTES SIN EII

- Personas no diagnosticadas de EII, ni de otras enfermedades inflamatorias, alérgicas, malignas o autoinmunes que se realicen, por indicación médica, una colonoscopia, y que ésta sea normal.

E.4

Principal exclusion criteria

Group 1: Patients with IBD

- Under 18 years old.
- Having an immune-mediated disease other than IBD at the baseline visit.
- Having a neoplasm or an active infection at the time of the baseline visit.
- Pregnancy or lactation.
- Alcohol or drug abuse.
- Ostomy.
- Abdominal surgery in the last 6 months.
- Colectomy in patients with UC.
- Active infection with hepatitis B, C or HIV virus.
- Indication of biologic treatment for a cause other than IBD.
- Indication of biologic treatment to prevent postoperative recurrence in CD.
- Have previously received a biologic drug with the same mechanism of action of the drug indicated by your doctor (anti-TNFα, anti-α4β7 or anti-p40).
- Refusal to give consent for participation in the study.

Group 2: patients without IBD

- Under 18 years old.
- Advanced chronic disease or any other pathology that prevents the follow-up of the protocol of this study.
- Pregnancy or lactation.
- Active infection with hepatitis B, C or HIV virus.
- Alcohol or drug abuse.
- Finding of macroscopic alterations during the ilecolonoscopy, or finding of relevant inflammatory alterations in the biopsies obtained during the ilecolonoscopy.
- Treatment with immunomodulators, immunosuppressants, corticosteroids or other drugs that alter the immune system.
- Refusal to give consent for participation in the study.

GRUPO 1: PACIENTES CON EII

- Menores de 18 años.
- Padecer una enfermedad inmunomediada distinta de la EII en la visita basal.
- Padecer una neoplasia o una infección activa en el momento de la visita basal.
- Embarazo o lactancia.
- Abuso de alcohol o drogas.
- Ostomía.
- Cirugía abdominal en los últimos 6 meses.
- Colectomía en los pacientes con CU.
- Infección activa por virus de la hepatitis B, C o VIH.
- Indicación del tratamiento biológico por otra causa distinta de la EII.
- Indicación del tratamiento biológico para prevenir la recurrencia postquirúrgica en la EC.
- Haber recibido previamente un fármaco biológico con el mismo mecanismo de acción del fármaco indicado por su médico (anti-TNFα, anti-α4β7 o anti-p40).
- Negativa a dar el consentimiento para la participación en el estudio.

GRUPO 2: PACIENTES SIN EII

- Menores de 18 años.
- Enfermedad crónica avanzada o cualquier otra patología que impida el seguimiento del protocolo de este estudio.
- Embarazo o lactancia.
- Infección activa por virus de la hepatitis B, C o VIH.
- Abuso de alcohol o drogas.
- Hallazgo de alteraciones macroscópicas durante la realización de la colonoscopia, o hallazgo de alteraciones inflamatorias relevantes en las biopsias obtenidas durante la colonoscopia.
- Tratamiento con inmunomoduladores, inmunosupresores, corticoides u otros fármacos que alteren el sistema inmune.
- Negativa a dar el consentimiento para la participación en el estudio.

E.5 End points

E.5.1

Primary end point(s)

Endoscopic response (main endpoint):

- In patients with CD, the endoscopic response will be defined as a >50% decrease in the SES-CD [78] 14 weeks after starting the biologic treatment. As a secondary variable, endoscopic response will be also defined as a decrease ≥3 points in the SES-CD (considered as a clinically significant endoscopic improvement) [80]. There is consensus that the evaluation of the response to treatment (and therefore the consideration of a patient as a primary non-responder) should not be performed before week 12-14 (in patients treated with anti-TNFα drugs) [13, 19, 81].
- In patients with UC, the endoscopic response will be defined as a decrease of ≥1 point in the Mayo endoscopic sub-score [82] 14 weeks after starting the biologic treatment.

Respuesta endoscópica (variable principal de valoración):

- En los pacientes con EC, la respuesta endoscópica se definirá como una disminución >50% en el SES-CD(78) 14 semanas después de haber iniciado el tratamiento biológico. Se evaluará también como variable secundaria la respuesta endoscópica definida como una diminución ≥3 puntos en el SES-CD (considerado como una mejoría endoscópica clínicamente significativa)(80) en la semana 14. Existe consenso en que la evaluación de la respuesta al tratamiento (y por tanto la consideración de un paciente como no respondedor primario) no debe realizarse antes de la semana 12-14 (en los pacientes tratados con fármacos anti-TNFα)(13, 19, 81).
- En los pacientes con CU, la respuesta endoscópica se definirá como una disminución ≥1 punto en el subíndice endoscópico del índice de Mayo(82) 14 semanas después de haber iniciado el tratamiento biológico.

E.5.1.1

Timepoint(s) of evaluation of this end point

14 weeks

14 semanas

E.5.2

Secondary end point(s)

Endoscopic activity:

- In patients with CD, it will be evaluated using the Simplified Endoscopic Activity Score for Crohn's Disease [64, 76-78] (SES-CD); Endoscopic activity will be considered when the SES-CD is ≥3. In operated patients, or in those where the endoscopic exploration is incomplete, the SES-CD will be calculated according to the explorable segments, considering the previously described activity criterion.
- In patients with UC, it will be evaluated by the Mayo endoscopic sub-score [61, 79]; endoscopic activity will be considered as ≥2.
- The assessment of endoscopic activity will be carried out centrally by sending anonymized endoscopic images.

Endoscopic remission:

- In patients with CD, endoscopic remission will be defined as a SES-CD ≤2, 14 weeks after starting the biologic treatment.
- In patients with UC, endoscopic remission will be defined as an endoscopic subscript ≤1, 14 weeks after starting the biologic treatment.

Clinical activity:

- In patients with CD, it will be evaluated using the Crohn's Disease Activity Index (CDAI) [83]. Clinical remission will be considered as a CDAI <150 points 14 weeks after starting the biologic treatment; and clinical response, reduction of CDAI by 100 (R-100) or 70 points (R-70) [83].
- In patients with UC it will be evaluated by the partial Mayo index [83]. Clinical remission will be considered as a partial Mayo index ≤2, with all the scores (of the partial index) of 1 as a maximum and with a sub-score of rectal bleeding of 0, 14 weeks after starting the biologic treatment [83]; and clinical response, the decrease of 3 or more points (of the partial index) with respect to the baseline situation [84].

Actividad endoscópica:

- En los pacientes con EC se evaluará mediante el Simplified Endoscopic Activity Score for Crohn’s Disease(64, 76-78) (SES-CD); se considerará que existe actividad endoscópica cuando el SES-CD sea ≥3. En pacientes operados, o en aquellos donde la exploración endoscópica sea incompleta, el SES-CD se calculará atendiendo a los segmentos explorables, considerándose el criterio de actividad previamente descrito.
- En los pacientes con CU se evaluará mediante el subíndice endoscópico del índice de Mayo(61, 79); se considerará actividad endoscópica un subíndice endoscópico ≥2.
- La valoración de la actividad endoscópica se realizará de forma centralizada mediante el envío de imágenes endoscópicas anonimizadas.

Remisión endoscópica:

- En los pacientes con EC, la remisión endoscópica se definirá como un SES-CD ≤2, 14 semanas después de haber iniciado el tratamiento biológico.
- En los pacientes con CU, la remisión endoscópica se definirá como un subíndice endoscópico ≤1, 14 semanas después de haber iniciado el tratamiento biológico.

Actividad clínica:

- En los pacientes con EC se evaluará mediante el Crohn's Disease Activity Index (CDAI)(83). Se considerará remisión clínica un CDAI <150 puntos en la EC, 14 semanas después de haber iniciado el tratamiento biológico; y respuesta clínica, la reducción del CDAI en 100 (R-100) o 70 puntos (R-70)(83).
- En los pacientes con CU se evaluará mediante el índice de Mayo parcial(83). Se considerará remisión clínica un índice de Mayo parcial ≤2, con todas las puntuaciones (del índice parcial) de 1 como máximo y con una subpuntuación de rectorragia de 0, 14 semanas después de haber iniciado el tratamiento biológico(83); y respuesta clínica, el descenso de 3 o más puntos (del índice parcial) respecto a la situación basal(84).

E.5.2.1

Timepoint(s) of evaluation of this end point

14 weeks

14 semanas

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

última visita del paciente

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

180

F.4.2

For a multinational trial

F.4.2.1

In the EEA

180

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)

traducir

El tratamiento se asignará por práctica clínica y bajo el criterio del investigador de cada uno de los centros. Por lo tanto antes de iniciar el ensayo, como una vez finalizado será el médico responsable el que bajo su juicio clínico decida cual es la opción terapéutica más adecuada.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-12-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-12-26

P. End of Trial
P.	End of Trial Status	Ongoing

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