Clinical Trials Register

Summary
EudraCT Number:	2011-005762-38
Sponsor's Protocol Code Number:	M13-393
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:	2012-11-23
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-005762-38

A.3

Full title of the trial

A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Coadministration of ABT-450 with Ritonavir (ABT-450/r) and ABT-267 in Adults with Chronic Hepatitis C Virus Infection (PEARL-I).

Sperimentazione Randomizzata in Aperto per la Valutazione della Sicurezza ed Efficacia della Co-somministrazione di ABT-450 e Ritonavir (ABT 450/r) e ABT-267 in Adulti affetti da Infezione Cronica da Virus dell'Epatite C (PEARL-I).

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 Co-administration of ABT-450 with Ritonavir (ABT-450/r) and ABT-267 in Adults with Chronic Hepatitis C Virus Infection.

Sperimentazione per Valutare la Sicurezza e gli Effetti della Co-somministrazione di ABT-450 e Ritonavir (ABT 450/r) e ABT-267 in Adulti affetti da Infezione Cronica da Virus dell’Epatite C.

A.4.1

Sponsor's protocol code number

M13-393

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	Abbott Laboratories
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	Abbott Laboratories
B.5.2	Functional name of contact point	EU Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Abbott House, Vanwall Business Park
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL64XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 1628 77 4695
B.5.5	Fax number	+44 1628 64 4330
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	NA
D.3.2	Product code	ABT-450
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.3.9.2	Current sponsor code	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	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: 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	NA
D.3.2	Product code	ABT-267
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.3.9.2	Current sponsor code	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	25
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.2.1.1.1	Trade name	Norvir
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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, 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	RITONAVIR
D.3.9.1	CAS number	155213-67-5
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	100
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

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	10008909
E.1.2	Term	Chronic hepatitis
E.1.2	System Organ Class	10019805 - Hepatobiliary disorders

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 is to assess the safety and efficacy (the percentage of subjects with HCV RNA < LLOQ 12 weeks after the last actual dose of study drug [SVR12 actual]) of ABT-450/r and ABT- 267 among treatment naive and prior null responder to pegylated IFN (pegIFN) and ribavirin (RBV) genotype 1b HCV infected subjects.

L’obiettivo primario di questa sperimentazione è quello di valutare la sicurezza e l ‘efficacia (la percentuale dei soggetti con HCV RNA < LLOQ 12 settimane dopo la somministrazione dell’ultima dose effettiva del medicinale sperimentale [SVR12effettiva]) ) di ABT-450/r e ABT-267 mediante confronto fra soggetti affetti da Infezione Cronica da Virus dell’Epatite C di genotipo 1b naïve rispetto al trattamento e con risposta nulla (null responders) a una pregressa terapia con Interferone pegilato (pegIFN) e ribavirina RBV.

E.2.2

Secondary objectives of the trial

- To assess the safety and efficacy (the percentage of subjects with SVR12 actual) of two durations of ABT-450/r + ABT-267 among treatment naive genotype 1b HCV infected subjects. - To assess the safety and efficacy (the percentage of subjects with SVR12 actual) of ABT-450/r + ABT-267 among treatment naive genotype 1a and genotype 1b HCV infected subjects.

- Valutare la sicurezza e l’ efficacia (la percentuale di soggetti con SVR12effettiva) di due periodi di trattamento di ABT-450/ritonavir+ABT-267 fra soggetti, affetti da Infezione Cronica da Virus dell’Epatite C di genotipo 1b, naïve rispetto al trattamento. - Valutare la sicurezza e l’ efficacia (la percentuale di soggetti con SVR12effettiva) di ABT-450/ritonavir+ABT-267 fra soggetti, affetti da Infezione Cronica da Virus dell’Epatite C naïve rispetto al trattamento di genotipo 1a e genotipo 1b.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female between the age of 18 and 70 years, inclusive, at time of enrollment. 2. Subjects must meet one of the following categories: • Treatment-naïve: Subject has never received antiviral treatment for hepatitis C infection; •Prior null responders: Subject has documentation that they previously received pegIFN plus RBV for at least 10 weeks and failed to achieve a 2 log10 IU/mL HCV RNA decrease by Week 12 (Week 10 to Week 16). 3. Body mass index (BMI) is ≥ 18 to < 38 kg/m2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m). 4. Chronic HCV genotype 1-infection for at least 6 months prior to study screening. 5. Subject has plasma HCV RNA level > 10,000 IU/mL at Screening.

1. Soggetti di ambo i sessi e di età compresa fra 18 e 70 anni al momento dell'arruolamento. 2. Soggetti che rientrano in una delle seguenti categorie: • Naïve rispetto al trattamento: nessun trattamento antivirale pregresso per l'infezione da epatite C o • Risposta nulla (null responders) a una pregressa terapia: soggetti con documentata terapia precedente di almeno 10 settimane con pegIFN eRBV senza ottenere una riduzione pari a 2 log10 IU/ml dei livelli di HCV RNA alla settimana 12 (fra le Settimane 10 e 16). 3. Indice di massa corporea (BMI) compresa fra ≥ 18 e < 38 kg/m2. Il valore BMI viene calcolato dividendo il peso espresso in kilogrammi (kg) per l'altezza in metri (m) al quadrato. 4. Infezione cronica da HCV di genotipo 1 per almeno 6 mesi prima dello Screening nella sperimentazione. 5. Soggetti con livelli plasmatici di HCV RNA > 10.000 IU/mL allo Screening.

E.4

Principal exclusion criteria

1. History of severe, life-threatening or other significant sensitivity to any drug. 2. Females who are pregnant or breastfeeding. 3. Recent history of drug or alcohol abuse that could preclude adherence to the protocol. 4. Positive test result for hepatitis B surface antigen or anti-HIV antibodies. 5. Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis.

1. Storia di ipersensibilità grave, potenzialmente fatale o altrimenti significativa a qualsiasi farmaco. 2. Soggetti di sesso femminile che sono in stato di gravidanza o stanno allattando. 3. Storia recente di abuso di droga o di alcolici che potrebbe impedire l'aderenza al protocollo. 4. Positività al test per l’antigene di superficie dell’epatite B oppure per gli anticorpi anti-HIV. 5. Qualsiasi evidenza clinica presente o pregressa di cirrosi quale ascite, o varici esofagee, o biopsia pregressa che documenta la presenza di cirrosi.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the percentage of subjects with SVR12 actual (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug). The primary comparison will be between Groups 2 and 3. Additional comparisons between Groups 1 and 2 and Groups 2 and 4 will be performed, provided that Groups 1 and 4 are enrolled.

L’endpoint primario di efficacia è rappresentato dalla percentuale dei soggetti con SVR12 effettiva (HCV RNA ≤LLOQ 12 settimane dopo l’ultima dose effettiva del medicinale sperimentale). Il principale confronto verrà effettuato fra il Gruppo 2 ed il Gruppo 3. Verranno effettuati ulteriori confronti fra Gruppo 1 e Gruppo 2 e fra Gruppo 2 e Gruppo 4 , se verranno arruolati soggetti nell’ambito dei Gruppi 1 e 4.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after last dose of study drug.

12 settimane dopo la somministrazione dell’ultima dose del medicinale sperimentale.

E.5.2

Secondary end point(s)

● The percentage of subjects with SVR24 actual (HCV RNA < LLOQ 24
weeks after the last actual dose of study drug),
● The percentage of subjects with EOTR (HCV RNA < LLOQ at Week 8 for
Group 1 or at Week 12 for Groups 2, 3 and 4).
For each secondary efficacy variable, comparisons between Groups 1 and
2, Groups 2 and 3, and Groups 2 and 4 will be performed, provided that
Groups 1 and 4 are enrolled.

• Percentuale dei soggetti con SVR24 effettiva (HCV RNA < LLOQ 24 settimane dopo l’ultima dose effettiva del medicinale sperimentale),
• Percentuale di soggetti con EOTR (HCV RNA < LLOQ alla Settimana 8 per il Gruppo 1 o alla Settimana 12 per il Gruppo 2, 3 e 4).
Per ciascuna variabile di efficacia secondaria, verranno effetuati confronti tra Gruppo 1 e 2, Gruppo 2 e 3, e Gruppo 2 e 4, verranno arruolati soggetti nell’ambito dei Gruppi 1 e 4.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 weeks after last dose of study drug.

24 settimane dopo la somministrazione dell’ultima dose del medicinale sperimentale.

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

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)

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

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

Yes

E.8.2.3.1

Comparator description

Non applicabile

Not applicable

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

Puerto Rico

Turkey

United States

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

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:

140

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

160

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 DAA and who do not achieve and maintain virologic suppression (HCV RNA < LLOQ), or who relapse post DAA therapy, may be offered participation in a separate, Abbott-sponsored treatment study, or may be offered another off-study (non-Abbott) treatment regimen, as determined appropriate by the investigator.

A tutti i soggetti che hanno ricevuto almeno una dose di DAA e che non hanno raggiunto e mantenuto soppressione virologica (HCV RNA < LLOQ), o che hanno manifestato recidiva dopo terapia con DAA, potrebbe essere offeta la partecipazione in una sperimentazione separata con Abbott come promotore, o potrebbe essere offerto un altro regime di terapia non sperimentale (non Abbott), come ritenuto appropriato dallo sperimentatore.

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

2013-01-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-02-17

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