Clinical Trials Register

Summary
EudraCT Number:	2012-003687-52
Sponsor's Protocol Code Number:	M13-961
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-11
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-003687-52

A.3

Full title of the trial

A Randomized, Double-Blind, Controlled Study to Evaluate the Efficacy and Safety of the Combination of ABT-450/Ritonavir/ABT-267 (ABT 450/r/ABT-267) and ABT-333 With and Without Ribavirin (RBV) in Treatment-Naïve Adults with Genotype 1b Chronic Hepatitis C Virus (HCV) Infection (PEARL-III)

Studio randomizzato, in doppio cieco e controllato per valutare l'efficacia e la sicurezza della combinazione di ABT 450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) e ABT-333 con e senza Ribavirina (RBV) in soggetti adulti con infezione cronica da virus dell'epatite C (HCV) di genotipo 1b naive rispetto al trattamento (PEARL III).

A.3.1

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

A double-blind, placebo-controlled study to evaluate the safety and effect of three experimental drugs ABT-450, ABT-267, and ABT-333 with or without ribavirin in people with hepatitis C virus (HCV) that have not been treated before. ''Experimental'' means that they have not been approved by any regulatory agency for sale to the public.

Studio in doppio cieco, controllato verso placebo per valutare la sicurezza e l’efficacia di tre farmaci sperimentali ABT-450, ABT-267 e ABT-333 con o senza Ribavirina in soggetti affetti dal Virus dell’Epatite C (HCV) che non sono mai stati trattati prima. “Sperimentali” significa che non sono stati approvati da nessuna agenzia regolatoria per la vendita al pubblico.

A.4.1

Sponsor's protocol code number

M13-961

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	ABBOTT 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	+44 1628 644475
B.5.5	Fax number	+44 1628 644330
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.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Capsule
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	RIBAVIRINA
D.3.9.1	CAS number	36791-04-5
D.3.9.2	Current sponsor code	RIBAVIRINA
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
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

Chronic Hepatitis C Infection.

Infezione Cronica da Virus dell’Epatite C.

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis C Infection.

Infezione Cronica da Virus dell’Epatite 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	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 objective of this study are to compare the efficacy (SVR12) and safety of the combination of ABT-450/r/ABT-267 and ABT-333 administered with and without RBV for 12 weeks in treatment-naive HCV genotype 1b-infected adults without cirrhosis.

Gli obiettivi primari di questa sperimentazione sono di confrontare l’efficacia (SVR12) e la sicurezza della combinazione di ABT-450/r/ABT-267 e ABT-333, somministrati con e senza RBV per 12 settimane in adulti con infezione da HCV di genotipo 1 in assenza di cirrosi che siano naïve rispetto al trattamento.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to compare the percentage of subjects with a decrease in hemoglobin to below the lower limit of normal (LLN) while on treatment between treatment arms and to summarize the percentage of subjects with virologic failure during treatment and the percentage of subjects with relapse post-treatment in each of the treatment group.

Gli obiettivi secondari di questa sperimentazione sono di confrontare, tra i bracci di trattamento, la percentuale di soggetti con decremento dell’emoglobina al di sotto del limite inferiore di normalità (LLN) durante il trattamento, e di misurare la percentuale di soggetti con fallimento virologico durante il trattamento e la percentuale di soggetti con recidiva post-trattamento in ciascuno dei gruppi di trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Males or females 18 and 70 years old, inclusive -Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control -Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than 10,000 IU/mL at screening) -Subject has never received antiviral treatment for hepatitis C infection -No evidence of liver cirhosis.

• Soggetti di ambo i sessi e di età compresa fra 18 e 70 anni inclusi • Donne in post-menopausa da oltre 2 anni oppure chirurgicamente sterili o che adottino specifici metodi contraccettivi • Presenza di infezione cronica da HCV di genotipo 1 (livelli di HCV RNA maggiori di 10,000 IU/ml allo screening) • Soggetti che non abbiano mai ricevuto un trattamento antivirale per l’infezione da virus dell’epatite C. • Nessun evidenza di cirrosi epatica.

E.4

Principal exclusion criteria

-Significant sensitivity to any drug -Use of contraindicated medications within 2 weeks of dosing -Abnormal laboratory tests -Positive hepatitis B surface antigen and anti-Human Immunodeficiency Virus antibody.

• Sensibilità significativa a qualsiasi farmaco • Uso di farmaci controindicati entro le 2 settimane precedenti il trattamento • Risultati di laboratorio alterati • Positività all'antigene di superficie dell'Epatite B o agli anticorpi per il Virus dell’Immunodeficienza Umana.

E.5 End points

E.5.1

Primary end point(s)

1. Percentage of subjects in each treatment group with sustained virologic response 12 weeks post-treatment.

Percentuale di soggetti, in ciascun gruppo di trattamento, con risposta virologica sostenuta 12 settimane dopo il trattamento.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. 12 weeks after last dose of study drug.

12 Settimane dopo l’ultima dose di farmaco sperimentale.

E.5.2

Secondary end point(s)

1. Changes in hemoglobin laboratory values during treatment. 2. Percentage of subjects with virologic failure during treatment. 3. Percentage of subjects with virologic relapse after treatment.

1. Cambiamenti nei valori di laboratorio dell’Emoglobina durante il trattamento. 2. Percentuale di soggetti con fallimento virologico durante il trattamento 3. Percentuale di soggetti con recidiva dopo il trattamento.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. First dose of study drug until last dose of study drug. 2. Post-treatment Day 1 through post-treatment week 48. 3. Post-treatment Day 1 through post-treatment week 48.

1. Dalla prima dose di farmaco sperimentale fino all’ultima dose di farmaco sperimentale. 2. Dal giorno 1 dopo il trattamento fino alla settimana 48 dopo il trattamento. 3. Dal giorno 1 dopo il trattamento fino alla settimana 48 dopo il trattamento.

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

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

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

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)

E.8.2.2

Placebo

Yes

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

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

Israel

Mexico

Russian Federation

Turkey

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.

Ultima visita dell’ultimo soggetto.

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

Number of subjects for this age range:

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:

360

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

215

F.4.2.2

In the whole clinical trial

400

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 may participate in an Abbott observational study to evaluate the durability of virologic response for subjects who achieve SVR and subjects who fail treatment. All subjects who do not achieve and maintain virologic suppression (HCV RNA < LLOQ), or who relapse post DAA therapy, may enter another Abbott study including ABT-450/r + ABT 267 + pegIFN/RBV. Subjects may be offered another non-Abbott treatment as determined appropriate by the investigator.

Tutti i sogg. possono partecipare ad uno st. osservazionale Abbott per valutare la risp. virologica in sogg. che raggiungono la SVR e in sogg. che falliscono il trattamento. Tutti i sogg. che non raggiungano e non mantengano la soppress. virologica (HCV RNA < LLOQ), o che presentino una recidiva dopo terapia con DAA, possono partecipare ad un altro studio Abbott con ABT-450/r+ABT-267+pegIFN/RBV. Ai sogg. può essere offerto un altro trattam. non-Abbott, se ritenuto opportuno dal PI.

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

2013-02-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-25

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

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