Clinical Trials Register

Summary
EudraCT Number:	2011-000885-36
Sponsor's Protocol Code Number:	APPRECIA
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-11-29
Trial results	View 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

2011-000885-36

A.3

Full title of the trial

Multicentric, randomized double blind clinical trial and paralell groups to compare Adalimub vs Azatioprina efficacy prevention in Crhon disease post-surgical recurrency after 52 weeks of treatment

Ensayo clínico multicéntrico, aleatorizado, con simple ciego y de grupos paralelos para comparar la eficacia de Adalimumab con la de Azatioprina en la prevención de la recurrencia postquirúrgica en la enfermedad de Crohn después de 52 semanas de tratamiento

A.3.1

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

Adalimub treatment to prevent recurrency post-surgery in Crohn disease.

Tratamiento con Adalimumab para prevenir la recurrencia post-cirugía en la enfermedad de Crohn

A.3.2

Name or abbreviated title of the trial where available

APPRECIA

A.4.1

Sponsor's protocol code number

APPRECIA

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	GETECCU
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	Abbott Laboratories
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	GETECCU
B.5.2	Functional name of contact point	Dr. Fernando Gomollón
B.5.3	Address:
B.5.3.1	Street Address	Gran Vía nº 81 - 5º Dpto. 10
B.5.3.2	Town/ city	Bilbao
B.5.3.3	Post code	48011
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34944278855
B.5.5	Fax number	+34944278808
B.5.6	E-mail	info@congresosxxi.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	Humira
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories UK
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.3.1	Product name	Humira
D.3.4	Pharmaceutical form	Solution for injection
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	Adalimumab
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Adalimumab
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	160
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Yes
D.3.11.13.1	Other medicinal product type	un anticuerpo monoclonal humano recombinante expresado en células de Ovario de Hámster Chino.
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Imurel
D.2.1.1.2	Name of the Marketing Authorisation holder	UCB Pharma, S.A.
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.3.1	Product name	Imurel
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Azatioprina
D.3.9.1	CAS number	6336-41-0
D.3.9.3	Other descriptive name	Imurel
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	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Comparator
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	Flagyl
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-aventis Francia
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.3.1	Product name	Flagyl
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Metronidazol
D.3.9.1	CAS number	99616-64-5
D.3.9.3	Other descriptive name	Flagyl
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	125
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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

Compare efficay of Adalimub vs Azatioprina to prevent surgical intervention in Chron disease

comparar la eficacia de Adalimumab con la de Azatioprina para prevenir la intervencion postquirúrgica en la enfermedad de Crohn

E.1.1.1

Medical condition in easily understood language

Crohn disease surgery recurrency

recurrencia de la cirugía en la enfermedad de Crohn

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluar la eficacia de Adalimumab vs. Azatioprina en la prevención de la recurrencia endoscópica (cuantificada con el Indice de Rutgeerts y definida como un índice de 2b, 3 ó 4) en la Enfermedad de Crohn tras 52 semanas de tratamiento.

E.2.2

Secondary objectives of the trial

-Comparar el porcentaje de pacientes en remisión clínica tras 24 y 52 semanas de tratamiento con Adalimumab o Azatioprina utilizando como variable de medida el Índice de Actividad de la Enfermedad de Crohn (CDAI), considerando como inactividad una puntuación menor o igual 200.
-Evaluar la eficacia de Adalimumab en la prevención de la recurrencia post-quirúrgica medida por Entero-RM en la semana 52.
-Evaluar la correlación entre la remisión endoscópica y la Entero-RM.
-Comparar el porcentaje de pacientes que requieren hospitalización con Adalimumab o Azatioprina en la semana 52.
-Evaluar los cambios en los marcadores de actividad de la enfermedad, tales como calprotectina fecal, proteína C reactiva y VSG en las semanas 24 y 52.
-Comparar el porcentaje de pacientes que requieren cirugía con Adalimumab o Azatioprina hasta la semana 52.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Edad mayor o igual a 18 años cumplidos en el momento de la firma del consentimiento informado.
-Pacientes de ambos sexos.
-Pacientes con enfermedad de Crohn a los que se les haya realizado una resección ileocecal/ileocolica (L1 o L3).
-Pacientes con reconstrucción quirúrgica con anastomosis ileocólica.
-Pacientes con o sin respuesta previa a IMM y anti-TNF.
-Las mujeres con capacidad fértil no deberán estar amamantando y deberán tener un test de embarazo en orina negativo y deberán comprometerse a utilizar métodos anticonceptivos con un índice de fracasos < 1% (ej., anticonceptivos orales, métodos de doble barrera, dispositivos intrauterinos), salvo que solo tengan una única pareja y que ésta sea estéril.-Pacientes que hayan firmado y fechado el formulario de consentimiento informado antes de realizar cualquier procedimiento de selección específico para el estudio.

E.4

Principal exclusion criteria

-Resección que requiera ileostomía temporal.
-Resección de urgencia que no permita completar el protocolo inicial de evaluación.
-Resección debida a estenosis indolente corta (< 10 cm) inactiva.
-Resección con enfermedad mucosa macroscópica residual en la anastomosis.
-Previa intolerancia o reacción adversa moderada o grave a adalimumab o azatioprina.
-Cualquier contraindicación o renuencia a realizar las colonoscopias o resonancias programadas.
-Contraindicaciones al tratamiento con Adalimumab, entre las que se incluyen, entre otras, las siguientes: tuberculosis activa, infecciones graves como la sepsis o las infecciones oportunistas, insuficiencia cardíaca moderada o grave (NYHA clases III o IV), tratornos desmielinizantes del sistema nervioso central, antecedentes de neoplasia maligna o de enfermedades autoinmunes.
-Manifestaciones extraintestinales graves asociadas.
-Fracaso anterior a adalumumab, azatioprina o mercaptopurina como prevención de recurrencia postquirúrgica.
-Cualquier otra enfermedad o condición del paciente por la que, a juicio del investigador, no es adecuada la participación del paciente en el estudio.

E.5 End points

E.5.1

Primary end point(s)

-Indice de recurrencia endoscópica en la Enfermedad de Crohn tras 52 semanas de tratamiento utilizando el índice de Rutgeerts, definiendo la recurrencia como un índice de 2b, 3 ó 4.

E.5.1.1

Timepoint(s) of evaluation of this end point

52 semanas

E.5.2

Secondary end point(s)

-Porcentaje de pacientes en remisión clínica tras 24 y 52 semanas de tratamiento con Adalimumab o Azatioprina utilizando como variable de medida el Índice de Actividad de la Enfermedad de Crohn (CDAI), considerando como inactividad una puntuación menor o igual 200.
-Entero-RM en la semana 52.
-Porcentaje de pacientes que requieren hospitalización en la semana 52.
-Cambios en los marcadores de actividad de la enfermedad, tales como calprotectina fecal, proteína C reactiva y VSG en las semanas 24 y 52.
-Porcentaje de pacientes que requieren cirugía hasta la semana 52.
-Cambios en la calidad de vida (medidos por los indices SIBDQ y Euro QoL) en las semanas 24 y 52.
-Acontecimientos adversos con Adalimumab o Azatioprina.

E.5.2.1

Timepoint(s) of evaluation of this end point

52 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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3.1

Comparator description

Azatioprina

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

No aplica

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:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

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)

Not apply

No aplica

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

2011-12-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-12

P. End of Trial
P.	End of Trial Status	Completed

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