Clinical Trials Register

Summary
EudraCT Number:	2012-004792-39
Sponsor's Protocol Code Number:	M12-999
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:	2013-03-05
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2012-004792-39

A.3

Full title of the trial

Open-label, Single Arm, Phase 2 Study to Evaluate the Safety and Efficacy of the Combination of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 Coadministered with Ribavirin (RBV) in Adult Liver Transplant Recipients with Genotype 1 Hepatitis C Virus (HCV) Infection

Estudio de fase 2, abierto, de un solo grupo, para evaluar la seguridad y la eficacia de la combinación de ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267) y ABT-333 administrados junto con ribavirina (RBV) en
adultos receptores de un trasplante hepático e infectados por el virus de la hepatitis C (VHC) de genotipo 1

A.3.1

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

A Study to Evaluate the Safety and Effect of three experimental drugs ABT?450, ABT-267 and ABT-333 in combination with Ribavirin in people who have had a Liver Transplant and have Hepatitis C Virus (HCV) infection. "Experimental" means that they have not been approved by any regulatory agency for sale to the public.

Un estudio para evaluar la seguridad y eficacia de tres fármacos experimentales ABT- 450, ABT- 267 y ABT333 administrados junto con Ribavirina en personas con un transplante hepático y con infección crónica por el virus de la hepatitis C (VHC). "Experimental" significa que no han sido aprobados por ninguna agencia reguladora para su venta al público.

A.4.1

Sponsor's protocol code number

M12-999

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	AbbVie Deutschland GmbH & Co. KG
B.1.3.4	Country	Germany
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	AbbVie Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AbbVie Ltd.
B.5.2	Functional name of contact point	euclinicaltrials@abbott.com
B.5.3	Address:
B.5.3.1	Street Address	Abbott House, Vanwall Business Park, Vanwall
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441628644475
B.5.5	Fax number	+441628644330
B.5.6	E-mail	euclinicaltrials@abbott.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	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	ABT-450/r/ABT-267
D.3.2	Product code	ABT-450/r/ABT-267
D.3.4	Pharmaceutical form	Film-coated 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	ABT-450
D.3.9.2	Current sponsor code	ABT-450
D.3.9.3	Other descriptive name	ABT-450
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	75
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RITONAVIR
D.3.9.1	CAS number	155213-67-5
D.3.9.2	Current sponsor code	RITONAVIR
D.3.9.4	EV Substance Code	SUB10342MIG
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABT-267
D.3.9.2	Current sponsor code	ABT-267
D.3.9.3	Other descriptive name	ABT-267
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	12.5
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	ABT-333
D.3.2	Product code	ABT-333
D.3.4	Pharmaceutical form	Film-coated 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	ABT-333
D.3.9.2	Current sponsor code	ABT-333
D.3.9.3	Other descriptive name	ABT-333
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	250
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	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.2.5	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	Ribavirin
D.3.2	Product code	Ribavirin
D.3.4	Pharmaceutical form	Film-coated 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.3.9.2	Current sponsor code	RIBAVIRIN
D.3.9.3	Other descriptive name	RIBAVIRIN
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.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

Chronic Hepatitis C Infection

Infección Crónica por el virus de la Hepatis C

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis C Infection

Infección Crónica por el virus de la Hepatis 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	15.1
E.1.2	Level	PT
E.1.2	Classification code	10008912
E.1.2	Term	Chronic hepatitis C
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

The primary objectives of this study are to assess safety and efficacy (the percentage of subjects achieving a 12-week sustained virologic response, SVR12 (HCV ribonucleic acid [RNA] < lower limit of quantification [LLOQ] 12 weeks following treatment) of coformulated ABT-450/r and ABT-267 (ABT-450/r/ABT-267) and ABT-333 coadministered with RBV for 24 weeks in HCV genotype 1-infected adult liver transplant recipients.

Los objetivos principales de este estudio consisten en evaluar la seguridad y la eficacia (porcentaje de
sujetos que logren una respuesta virológica mantenida a las 12 semanas, RVM12 (ácido ribonucleico (ARN) del VHC < límite inferior de cuantificación (LIC), 12 semanas después del tratamiento) de ABT-450 en formulación conjunta con ritonavir (r) y ABT-267 (ABT-450/r/ABT-267) y ABT-333 administrado conjuntamente con ribavirina (RBV) durante 24 semanas en receptores adultos de un trasplante hepático con infección recurrente por el VHC de genotipo 1.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to assess the percentage of subjects achieving a 24-week sustained virologic response, SVR24 (HCV RNA < LLOQ 24 weeks following treatment), the percentage of subjects with virologic failure during treatment, and the percentage of subjects with relapse post-treatment.

Los objetivos secundarios de este estudio consisten en evaluar el porcentaje de sujetos con fracaso virológico durante el tratamiento, el porcentaje de sujetos que logren una respuesta virológica mantenida a las 24 semanas, RVM24 (ARN del VHC < LIC, 24 semanas después del tratamiento) y el porcentaje de sujetos con recidiva después del tratamiento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female between the ages of 18 and 70 years, inclusive, at time of enrollment.
2. Liver transplantation as a consequence of HCV infection no less than 12 months before the Screening Visit.
3. A liver biopsy which shows evidence of fibrosis ? F2 (Metavir scale) within 3 months prior to or during the Screening Period.
4. Screening laboratory result indicating HCV genotype 1 infection.
5. Currently taking an immunosuppressant regimen based on either tacrolimus or cyclosporine where doses of immunosuppressant drugs have not been increased over the 3 months prior to Screening and no new drugs have been added for at least 3 months before Screening. Corticosteroids such as prednisone or prednisolone are permitted as components of the immunosuppressant regimen providing the dose is not more than 5 mg/day.

1. Varones o mujeres con una edad comprendida entre los 18 y 70 años, ambos inclusive, en el momento de inclusión.
2. Trasplante hepático como consecuencia de la infección por el VHC no menos de 12 meses antes de la visita de selección.
3. Biopsia hepática que revele datos de fibrosis ? F2 (escala de puntuación Metavir) en los 3 meses previos al período de selección o durante el mismo.
4. Resultado analítico en la selección indicativo de una infección por el VHC de genotipo 1.
5. Tratamiento presente con un régimen inmunosupresor a base de tacrolimus o ciclosporina en el que no se han aumentado las dosis de inmunosupresores durante los 3 meses previos a la selección y no se han añadido fármacos nuevos durante, al menos, 3 meses antes de la selección. Se permite el uso de corticosteroides, como prednisona o prednisolona, como componentes del régimen inmunosupresor, siempre que la dosis no sea superior a 5 mg/día.

E.4

Principal exclusion criteria

- Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab).
- Clinically significant abnormalities, other than HCV infection in a subject post transplant, based upon the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG) that make the subject an unsuitable candidate for this study in the opinion of the investigator.
- Recent (within 6 months prior to study drugs administration) history of drug or alcohol abuse that, in the opinion of the investigator, could preclude adherence to the protocol.
- Previous use of any investigational or commercially available anti-HCV agent other than IFN-based therapy, i.e. conventional (c)IFN and/or pegylated (Peg) IFN, with or without RBV, including previous exposure to ABT-450, ABT-333 or ABT-267.

- Resultado positivo en el análisis del antígeno de superficie del virus de la hepatitis B (HbsAg) o de anticuerpos contra el virus de la inmunodeficiencia humana (Ac anti-VIH).
- Anomalías clínicamente importantes, aparte de la infección por el VHC, después del trasplante, basadas en los resultados de la anamnesis, la exploración física, las constantes vitales, las pruebas
analíticas y un electrocardiograma (ECG) de 12 derivaciones que hacen que, en opinión del investigador, el sujeto no sea un candidato adecuado para este estudio.
- Antecedentes recientes (en los 6 meses previos a la administración de los fármacos del estudio) de alcoholismo o toxicomanía que, en opinión del investigador, podrían impedir el cumplimiento del protocolo.
- Uso previo de cualquier fármaco en investigación o comercializado contra el VHC distinto de un tratamiento a base de interferón (IFN), es decir, IFN convencional (IFNc) o pegilado (IFNpeg), con o sin RBV, incluida la exposición previa a ABT-450, ABT-333 o ABT-267.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the percentage of subjects with SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drugs).

El criterio de valoración principal es el porcentaje de sujetos con RVM12 (ARN del VHC < LIC, 12 semanas después de la última dosis real de los fármacos del estudio).

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after last dose of study drugs

12 semanas después de la última dosis de los fármacos del estudio

E.5.2

Secondary end point(s)

The secondary endpoints are:
? The percentage of subjects with SVR24 (HCV RNA < LLOQ 24 weeks after the last actual dose of study drugs);
? The percentage of subjects with virologic failure during treatment;
? The percentage of subjects with post-treatment relapse.

Los objetivos secundarios de este estudio consisten en evaluar:
? El porcentaje de sujetos con RVM24 (ARN del VHC < LIC 24 semanas después de la última dosis real de los fármacos del estudio);
? El porcentaje de sujetos con fracaso virológico durante el tratamiento;
? El porcentaje de sujetos con recidiva después del tratamiento

E.5.2.1

Timepoint(s) of evaluation of this end point

Treatment Day 1 to end of treatment and end of treatment to 48 weeks post treatment.

Desde el Día 1 de tratamiento hasta el final del tratamiento, y desde el final del tratamiento hasta 48 semanas después (Periodo Posterior al Tratamiento)

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

Yes

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

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

United States

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

Last Subject Last Visit

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:

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

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

All subjects who receive at least one dose of direct acting antiviral agent (DAA) and who do not achieve and maintain virologic supression (HCV RNA less than lower limit of quantification), or who relapse post DAA therapy, may be offered participation in a separate, AbbVie-sponsored treatment study, or may be offered another off-study (non-AbbVie) treatment regimen, as determined appropriate by the investigator.

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

2013-02-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-07-13

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials