Clinical Trials Register

Summary
EudraCT Number:	2011-003559-21
Sponsor's Protocol Code Number:	CDEB025A2212
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:	2012-01-13
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

2011-003559-21

A.3

Full title of the trial

A Retrospective Pharmacogenetic Analysis of Hepatitis C Patients treated with Alisporivir (DEB025) Alone or in Combination with Peg-IFN2a and/or Ribavirin

Análisis farmacogenético retrospectivo de pacientes con hepatitis C tratados con Alisporivir (DEB025) Solo o en Combinación con Peg-IFN2a y/o Ribavirina

A.3.1

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

Pharmacogenetic analysis study of hepatitis C patients treated with DEB025/Alisporivir alone or with Peg-IFN2a and/or Ribavirin

Análisis farmacogenético retrospectivo de pacientes con hepatitis C tratados con Alisporivir (DEB025) Solo o en Combinación con Peg-IFN2a y/o Ribavirina

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CDEB025A2212

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	Novartis Farmaceutica 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	Novartis Farmaceutica
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	Novartis Farmaceutica
B.5.2	Functional name of contact point	Inmaculada Bosch Tirau
B.5.3	Address:
B.5.3.1	Street Address	Gran via de les corst catalanes 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34933064342
B.5.5	Fax number	+34933064290
B.5.6	E-mail	eecc.novartis@novartis.com

D. IMP Identification
D.IMP: 1
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
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Tablet
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	RIBAVIRIN
D.3.9.1	CAS number	36791-04-5
D.3.9.4	EV Substance Code	SUB10297MIG
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)	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	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	Alisporivir
D.3.2	Product code	DEB025
D.3.4	Pharmaceutical form	Capsule, soft
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	Alisporivir
D.3.9.1	CAS number	25443509505
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)	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	Pegasys,180 microgramos, solucion 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.3.1	Product name	Pagasys
D.3.2	Product code	02221007
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEGINTERFERON ALFA-2A
D.3.9.1	CAS number	198153-51-4
D.3.9.4	EV Substance Code	SUB16452MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(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)	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
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 and how biomarkers affect the response to treatment of the disease

Hepatitis C y como los biomarcadores afectan en la respuesta al tratamiento en esta patologia.

E.1.1.1

Medical condition in easily understood language

Hepatitis C

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10021881
E.1.2	Term	Infections and infestations
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the impact of potential markers (or polymorphisms) in host genes from patients in studies DEB-025-103, DEB-025-HCV-203 and DEB-025-HCV-205 on the PK profile, safety, and efficacy of alisporivir alone or in combination with peg-IFN-2a and ribavirin. These potential markers may include variants in cytochrome P450 isoenzymes 2D6 and 3A5, transporters such as P-gp, UGT1A1, cyclophilin A and B, IL28B, among others.

? Examinar la asociación de la variación genética individual en la respuesta virológica precoz después de 2 y 4 semanas en pacientes tratados con alisporivir solo (monoterapia) en DEB-025-103 y DEB-025-HCV-203, respectivamente
? Examinar la asociación de la variación genética individual en la tasa de RVS en los pacientes tratados con alisporivir en combinación con Peg-IFN2? y ribavirina durante 24 ó 48 semanas en DEB-025-205

E.2.2

Secondary objectives of the trial

? Examinar la asociación de la variación genética individual en la RVR, en la respuesta virológica en la Semana 12 y en la respuesta al final del tratamiento en los pacientes tratados con alisporivir en combinación con Peg-IFN2? y ribavirina en DEB-025-205
? Examinar la asociación de la variación genética individual en la elevación del nivel de bilirrubina en tratamiento en DEB-025-103, DEB-025-HCV-203 y DEB-025-HCV-205
? Examinar la asociación de la variación genética individual en las propiedades farmacocinética de alisporivir en DEB-025-103, DEB-025-HCV-203 y DEB-025-HCV-205
? Evaluar la durabilidad de la respuesta virológica sostenida midiendo el ARN del VHC en pacientes que finalizaron DEB-025-HCV-205
? Evaluar la función hepática bioquímica de los pacientes que finalizaron DEB-025-HCV-205 a fin de determinar los cambios en la enfermedad hepática con el tiempo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must have completed studies DEB-025-103, DEB-025-HCV-203 and DEB-025-HCV-205. Written informed consent must be obtained prior to any assessments being performed.

Los pacientes elegibles para la inclusión en este estudio han de cumplir todos los criterios que se indican a continuación:
1. El consentimiento informado por escrito deberá obtenerse antes de realizar ninguna evaluación.
2. Los pacientes habrán completado ya sea los estudios DEB-025-103, DEB-025-HCV-203 o el estudio DEB-025-HCV-205.

E.4

Principal exclusion criteria

None

Ninguno

E.5 End points

E.5.1

Primary end point(s)

1) To examine the association of individual genetic variation on early viral response after 2 and 4 weeks of alisporivir monotherapy in DEB-025-103 and DEB-025-HCV-203, respectively

2) To examine the association of individual genetic variation on SVR rate in patients treated with alisporivir in combination with Peg-IFN-2a and ribavirin for 24 or 48 weeks in DEB-025-205

E.5.1.1

Timepoint(s) of evaluation of this end point

Retrospective pharmacogenetic analysis

Analisis farmacogenetico retrospectivo

E.5.2

Secondary end point(s)

1)To examine the association of individual genetic variation on RVR, viral response at Week 12 and end of treatment response in patients treated with alisporivir in combination with Peg-IFN-2a and ribavirin in DEB-025-205

2)To examine the association of individual genetic variation on elevation of on-treatment bilirubin level in DEB-025-103, DEB-025-HCV-203 and DEB-025-HCV-205

3)To examine the association of individual genetic variation on pharmacokinetic property of alisporivir in DEB-025-103, DEB-025-HCV-203 and DEB-025-HCV-205

4) To evaluate the durability of sustained virologic response by measuring HCV RNA in patients who completed DEB-025-HCV-205
5) To evaluate biochemical liver function of patients who completed DEB-025-HCV-205 to determine changes in liver disease over time

E.5.2.1

Timepoint(s) of evaluation of this end point

1-3) Retrospective pharmacogenetic analysis
4-5) At the time of sample analysis

1-3) Analisis farmacogenetico retrospectivo
4-5) En los tiempos de analisis de muestras

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Optional HCV RNA analysis, liver function and hematology testing of patients from study DEB-025-HCV-205

A los pacientes de DEB-025-HCV-205 se les dará la opción de que se les extraigan muestras para los análisis del ARN del VHC, pruebas de la función hepática, AFP, urea, electrolitos y hematología

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.3

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

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

Belgium

Canada

France

Germany

Italy

Poland

Romania

Spain

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

When all patients from studies DEB-025-103, DEB-025-HCV-203 and DEB-025-HCV-205 who consent to participate in this post-hoc pharmacogenetic analysis have provided blood samples over a 6 to 9 month recruitment period

Cuando todos los pacientes de los ensayos DEB-025-103, DEB-025-HCV-203 y DEB-025-HCV-205 que consientan participar en este ensayo farmacogenético retrospectivo den una muestra de sangre de las 6 a los 9 meses de reclutamiento.

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

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:

177

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-01-13.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

Yes

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.4.2

For a multinational trial

F.4.2.1

In the EEA

260

F.4.2.2

In the whole clinical trial

277

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)

None. This study involves a single blood draw for a pharmacogenetic assessment with an optional additional blood draw for patients who completed study DEB-025-HCV-205. No treatment is involved.

Ninguno. Este ensayo solo implica una extracción sanguinea para evaluación farmacogenetica y otras extracciones adicionales àra aquellos pacientes que participaron en el ensayo DEB-025-HCV-205. No hay tratamiento

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

2012-01-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-11-07

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