Clinical Trials Register

Summary
EudraCT Number:	2011-005740-95
Sponsor's Protocol Code Number:	M13-389
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-07-25
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

Austria - BASG

A.2

EudraCT number

2011-005740-95

A.3

Full title of the trial

A Randomized, Open-Label, Multicenter Study to Evaluate the Safety and Antiviral Activity of the Combination of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With and Without Ribavirin in Treatment-Experienced Subjects with Genotype 1b Chronic Hepatitis C Virus (HCV) Infection (PEARL–II)

Randomisierte, offene, multizentrische Studie zur Bewertung der
Sicherheit und antiviralen Wirksamkeit der Kombination von ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) und ABT-333 mit und ohne Ribavirin bei vorbehandelten Patienten mit chronischer Hepatitis-C-Virus-Infektion (HCV-Infektion) vom Genotyp 1b (PEARL-II)

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 people with HCV. "Experimental" means that they have not been approved by any regulatory agency for sale to the public.

Eine Studie zur Beurteilung der Sicherheit und Wirksamkeit von 3
experimentellen Medikamenten ABT-450, ABT-267 und ABT-33 bei
Menschen mit Hepatitis C. "Experimentell" bedeutet, dass noch keine
Zulassung zum Verkauf an die Öffentlichkeit durch eine Behörde erlangt
wurde.

A.4.1

Sponsor's protocol code number

M13-389

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	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	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44162877 4695
B.5.5	Fax number	+44162864 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	ABT-450/ritonavir/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.3.10	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.3.9.3	Other descriptive name	ABT-267
D.3.9.4	EV Substance Code	SUB32604
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.3.4	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.3.10	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.3.4	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.3.9.4	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

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	16.0
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 evaluate the safety of 12 weeks of treatment with ABT-450/r/ABT-267 and ABT-333 with and without RBV, and to show the non-inferiority in SVR12 rates (the percentage of subjects achieving a 12-week sustained virologic response, SVR12, [HCV RNA < LLOQ 12 weeks following therapy]) of both arms to the historical SVR rate of telaprevir plus pegIFN and RBV.

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) by the end of treatment with ABT-450/r/ABT-267 and ABT-333 with RBV and without RBV;
- To show the superiority in SVR12 rates of 12 weeks of treatment with ABT-450/r/ABT-267 and ABT-333 with and without RBV to the historical SVR rate of telaprevir plus pegIFN and RBV therapy;
- To show the non-inferiority in SVR12 rates of 12 weeks of treatment with ABT-450/r/ABT-267, and ABT-333 without RBV (3 DAA/12) to 12 weeks of treatment with ABT-450/r/ABT-267 and ABT-333 with RBV (3 DAA/RBV/12);
- 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 groups.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female and is between 18 and 70 years, inclusive, at time of screening.
2. Subject failed previous treatment with pegIFN and RBV
3. Chronic HCV genotype 1b-infection for at least 6 months prior to study Screening
4. Subject's HCV genotype is subgenotype 1b at Screening without co-infection with any other genotype/subgenotype.

E.4

Principal exclusion criteria

1. Recent history of drug or alcohol abuse
2. Positive test result for hepatitis B surface antigen (HBsAg) or anti-HIV antibodies (anti-HIV Ab).
3. Any current or past clinical evidence of cirrhosis
4. Any cause of liver disease other than chronic HCV infection.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoints are:
(1) SVR12: non inferiority of Arm 2 to the historical rate for telaprevir plus pegIFN/RBV.
(2) SVR12: non inferiority of Arm 1 to the historical rate for telaprevir plus pegIFN/RBV

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after last dose of study drugs

E.5.2

Secondary end point(s)

The secondary efficacy endpoints included in the fixed-sequence are:
(3) Comparison of the percentage of subjects with a decrease in hemoglobin to below the lower limit of normal (LLN) at the end of treatment with ABT-450/r/ABT-267 and ABT-333 with RBV versus without RBV.
(4) SVR12: Superiority of Arm 1 to the historical rate for telaprevir plus pegIFN/RBV
(5) SVR12: Superiority of Arm 2 to the historical rate for telaprevir plus pegIFN/RBV
(6) SVR12: Non-inferiority of Arm 2 to Arm 1.

Other secondary endpoints not included in the fixed sequence are:
● The percentage of subjects in each treatment group with virologic failure during treatment (defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment or confirmed HCV RNA ≥ LLOQ at the end of treatment), and
● The percentage of subjects in each treatment group with post-treatment relapse (defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of study drugs among subjects completing treatment and with HCV RNA < LLOQ at the end of treatment).

E.5.2.1

Timepoint(s) of evaluation of this end point

During treatment or at the end of treatment (last dose of study drug)

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)

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

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

Austria

Belgium

Italy

Netherlands

Puerto Rico

Sweden

Switzerland

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

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:

190

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

168

F.4.2.2

In the whole clinical trial

210

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 active DAA may be offered participation in an AbbVie-sponsored observational study to evaluate the durability of virologic response. Subjects receiving active DAA and who do not achieve and maintain virologic suppression, or relapse, may be offered another AbbVie-sponsored treatment study including ABT-450/r + ABT 267 + pegIFN/RBV. Subjects may also be offered another non-AbbVie treatment 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

2012-07-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-31

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-10-13

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