Clinical Trials Register

Summary
EudraCT Number:	2010-020033-14
Sponsor's Protocol Code Number:	CDEB025A2210
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:	2010-07-29
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

2010-020033-14

A.3

Full title of the trial

Estudio de fase II, multicéntrico, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos sobre la eficacia y seguridad de DEB025 combinado con peg-IFN alfa-2a y ribavirina en pacientes con hepatitis C crónica genotipo 1 no respondedores al tratamiento previo con peg-IFN alfa-2 más ribavirina

A.4.1

Sponsor's protocol code number

CDEB025A2210

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Farmacéutica S.A
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
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	DEB025
D.3.2	Product code	DEB025
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Alisporivir
D.3.9.2	Current sponsor code	DEB025
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	200
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	PEGASYS, 180 microgramos, solución inyectable en jeringa precargada
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
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	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	PEGINTERFERON ALFA 2A
D.3.9.3	Other descriptive name	PEGINTERFERON ALFA 2A
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	180
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Es conjugado covalente de la proteína interferón alfa-2a obtenido mediante tecnología del ADN recombinante de Escherichia Coli con bis – [monometoxipolietilenglicol].
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	COPEGUS 200 mg comprimidos recubiertos con película
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE FARMA, 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.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	RIBAVIRINA
D.3.9.1	CAS number	36791-04-5
D.3.9.3	Other descriptive name	RIBAVIRIN
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	200
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, soft
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hepatitis C crónica en pacientes genotipo 1

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	11
E.1.2	Level	LLT
E.1.2	Classification code	10008912
E.1.2	Term	<Manually entered code. Term in E.1.1>

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 si la proporción de pacientes que alcancen RVPc (por Límite de Cuantificación, LC, es decir, ARN del VHC < 25 UI/mL) tras 12 semanas de terapia triple con DEB025 600 mg/día combinado con peg-IFNα2a 180 µg 1x/semana y RBV 1000/1200 mg/día es más alta en comparación con la proporción de pacientes que alcancen RVPc tras 12 semanas de terapia con placebo equivalente al tratamiento con DEB025 más TR, que consiste en peg-IFNα2a 180 μg 1x/semana + RBV 1000/1200 mg/día en pacientes con hepatitis C crónica GT1 sin respuesta previa al TR

E.2.2

Secondary objectives of the trial

La variable de eficacia secundaria clave es la proporción de pacientes que alcancen RVS24, definida como ARN del VHC < LC al final del seguimiento postratamiento de 24 semanas. La comparación secundaria clave está entre el grupo con tratamiento activo (A) DEB025 600 mg más TR y el grupo control (C) placebo de DEB025 600 mg más TR en cuanto a la proporción de pacientes que alcancen RVS24.
Para ver otros objetivos secundarios, consultar protocolo (version 31May2010)

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

El estudio incluye un componente farmacogenético y farmacogenómico opcional con el objetivo de:
1.- evaluar el impacto que los posibles marcadores (o polimorfismos) en genes huésped tienen en el perfil Farmacocinético, en la seguridad y eficacia de DEB025 en combinación con el tratamiento de referencia, además de
2.- identificar biomarcadores predictivos de la respuesta al tratamiento mediante la utilización de datos genómicos del mRNA y miRNA para aumentar nuestro entendimiento de la base m

E.3

Principal inclusion criteria

1. Los pacientes elegibles para ser incluidos en este estudio deben cumplir todos los criterios que se indican a continuación:
2. El consentimiento informado por escrito debe obtenerse antes de que se realice ninguna de las evaluaciones.
3. Hombres o mujeres de ≥18 y ≤ 65 años de edad;
4. IMC entre ≥ 18 y ≤ 36 kg/m2;
5. HBsAg negativo y VIH negativo;
6. Infección vírica por hepatitis C crónica registrada y diagnosticada mediante dos pruebas realizadas a intervalos de al menos 6 meses (el diagnóstico inicial se puede basar en anticuerpos VHC positivos o medición cuantitativa o cualitativa de ARN del VHC). Además, será necesario confirmar la cronicidad mediante un resultado positivo en la prueba de ARN del VHC, es decir, RCPc (reacción de la cadena de la polimerasa cuantitativa); por tanto la segunda prueba se puede realizar en la selección;
7. Límite inferior del nivel plasmático del ARN del VHC ≥ 10000 UI/ml evaluado mediante RCPc (reacción de la cadena de la polimerasa cuantitativa) o equivalente en la selección; ningún límite superior;
8. Genotipo 1 del VHC;
9. No respondedores previos al TR (con peg-IFNa 2a o 2b y RBV) tras el tratamiento con la dosis plena durante al menos 12 semanas con ARN del VHC detectable al final del tratamiento. Deberán haber transcurrido un mínimo de 3 meses desde el último tratamiento del paciente cuando al paciente se le califique como un no respondedor y se realice el reclutamiento en este estudio.

E.4

Principal exclusion criteria

1. Tratamiento con cualquier fármaco anti-VHC (aprobado o en investigación) en los 3 meses previos a la selección en el ensayo actual.
2. Uso en curso o reciente de cualquier otra medicación (incluidos medicamentos de venta sin receta y productos a base de hierbas) en las 2 semanas previas al inicio del estudio
3. Antecedentes de hipersensibilidad a cualquiera de las medicaciones del estudio
4. Pacientes con signos de cirrosis en el momento de la selección. Es necesario que el estado no cirrótico de un paciente se confirme mediante biopsia de hígado realizada en los últimos 24 meses o mediante una elastografía transitoria (en los 6 meses anteriores a la selección).
5. Cáncer activo o sospecha de cáncer, o antecedentes de enfermedad maligna en la que el riesgo de recurrencia es ≥ 20 % en 2 años.
6. Antecedentes de signos clínicos de enfermedad cardiaca crónica o ECG con QTc > 450 mseg en hombres y > 470 mseg en mujeres (corrección de Fredericia) en la selección o en la visita basal.
7 y 8. Mujeres y hombres en edad fértil a no ser que cumplan con los criterios indicados en el protocolo
9. Mujeres embarazadas o en período de lactancia. Hombres cuyas parejas estén embarazadas o estén planteando quedarse embarazadas
10. Genotipo del VHC diferente al genotipo 1 o coinfección de GT1 más otro genotipo del VHC
11. Cualquier otra causa de hepatopatía relevante distinta al VHC
12. Enfermedad que, en opinión del Investigador haría que el paciente no fuese adecuado
13. Antecedentes de enfermedad psiquiátrica moderada, severa o incontrolada, especialmente depresión, incluidos los antecedentes de hospitalización o intento de suicidio
14. Hipertensión arterial incontrolada, es decir, pacientes con PA sistólica ≥ 160 mmHg y/o PA diastólica ≥ 100 mmHg
15. Antecedentes de pancreatitis, diabetes mellitus no controlada definida como glucosa sérica en ayunas > 140 mg/dL y HbA1c > 7,5 % (incluidos pacientes diabéticos en tratamiento con la medicación) o retinopatía
16. Título de ANA (anticuerpos antinucleares) > 1:640 en la selección y/o signos de hepatitis autoimmune en la biopsia del hígado
17. Consumo de alcohol > 20 g/día en mujeres y > 30 g/día en hombres.
18. Trasplante de órganos, que no sea trasplante de córnea o de pelo
19. Hemoglobinopatías (talasaemia mayor, anemia de células falciformes o drepanocitosis)
20. Antecedentes familiares de colestasis neoatal severa o colestasis del embarazo
21. Enfermedad de Gilbert
22. Recuento de neutrófilos < 1500/μL (< 1200/ μL en el caso de afroamericanos); Hb < 12 g/dL en mujeres y < 13 g/dL en hombres; plaquetas < 90 000/μL, recuento de leucocitos < 3000/mm3;
23. ALT ≥ 10 veces el LSN;
24. Enfermedad de Von Willebrandt
25. Corticoterapia por vía oral o intravenosa o inmunosupresión 3 meses antes de la selección o se prevé la necesidad de dicho tratamiento en el período de estudio completo. Se permite el uso de esteroides inhalados para el asma.
26. Antecedentes o signos actuales de hepatopatía descompensada (ascitis, hemorragia por varices, encefalopatía hepática u otros signos de hipertensión portal progresiva o insuficiencia hepática progresiva (protrombina INR > 1,5, albúmina sérica < 3,5g/dL), bilirrubina total > 1,8 mg/dL)
27. BUN o creatinina sérica > LSN (confirmada) y aclaramiento de creatinina < 50 mL/min (por Cockcroft-Gault o MDRD);
28. TSH > 1,5 veces el LSN. En caso de TSH ligeramente elevada (1- 1,5 veces el LSN), a los pacientes se les puede incluir si su T3 libre y T4 libre están dentro del intervalo normal.

E.5 End points

E.5.1

Primary end point(s)

proporción de pacientes que alcancen RVPc, definida
como ARN del VHC < LC al final del tratamiento de 12 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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.4

Double blind

Yes

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	25
F.4.2	For a multinational trial
F.4.2.1	In the EEA	150
F.4.2.2	In the whole clinical trial	258

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

2010-11-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-10-06

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

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Orphan Designation Number:
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