Clinical Trials Register

Summary
EudraCT Number:	2012-002777-56
Sponsor's Protocol Code Number:	ML28470
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:	2012-08-31
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

2012-002777-56

A.3

Full title of the trial

Cross-sectional multicenter study evaluating the IL28B polymorphism in patients with HBeAg-negative chronic hepatitis B treated with pegylated interferon alfa-2a in the course of Peg.Be.Liver study

Studio trasversale multicentrico per la valutazione del polimorfismo di IL28B in pazienti affetti da epatite B cronica HBeAg negativa, trattati con interferone Pegilato alfa-2a durante lo studio Peg.Be.Liver

A.3.1

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

A.4.1

Sponsor's protocol code number

ML28470

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	ROCHE
B.1.3.4	Country	Italy
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	Roche S.p.A
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Roche S.p.A.
B.5.2	Functional name of contact point	Head of Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Viale G.B. Stucchi 110
B.5.3.2	Town/ city	Monza
B.5.3.3	Post code	20900
B.5.3.4	Country	Italy
B.5.4	Telephone number	039 247 5070
B.5.5	Fax number	039 247 5084
B.5.6	E-mail	sergio.scaccabarozzi@roche.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	Yes
D.2.1.1.1	Trade name	Pegasys
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	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.3.9.2	Current sponsor code	RO0258310
D.3.9.4	EV Substance Code	SUB16452MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Covalent conjugate of the protein interferon alfa-2a, produced by recombinant DNA technology
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	Yes
D.2.1.1.1	Trade name	ZEFFIX
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXO GROUP LTD
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	LAMIVUDINE
D.3.9.1	CAS number	134678-17-4
D.3.9.4	EV Substance Code	SUB08392MIG
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	Yes
D.3.11.13.1	Other medicinal product type	-

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

HBeAg-negative chronic hepatitis B

Epatite cronica B HbAg negativa

E.1.1.1

Medical condition in easily understood language

chronic hepatitis B

Epatite cronica B

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	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10008910
E.1.2	Term	Chronic hepatitis B
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

Cross-sectional multicenter study evaluating the IL28B polymorphism in patients with HBeAg-negative chronic hepatitis B treated with pegylated interferon alfa-2a in the course of Peg.Be.Liver study.

E.2.2

Secondary objectives of the trial

• Evaluation of the association between IL28B polymorphism and HBsAg clearance observed at the end of treatment (EoT) and at the end of follow-up (EoF) in the predecessor ML18253 study;
• Evaluation of the association between IL28B polymorphism and HBsAg ≤ 10 IU/ml at EoT and EoF in the predecessor ML18253 study;
• Evaluation of the association of IL28B polymorphism and HBsAg kinetic in the predecessor ML18253 study

• Valutazione della correlazione tra i polimorfismi di IL28B e l'eliminazione di HBsAg osservata alla fine del trattamento (EoT) e alla fine del follow up (EoF) nello studio precedente ML18253;
• Valutazione della correlazione tra i polimorfismi di IL28B e HBsAg ≤ 10 UI/ml a EoT e a EoF nello studio precedente ML18253;
• Valutazione della correlazione tra i polimorfismi di IL28B e la cinetica di HBsAg nello studio precedente ML18253.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Signature of the informed consent form for participation in this study;
• Previous participation in study ML18253;
• Administration of at least one dose of the study drug during ML18253 study.

1. firma del consenso informato per la partecipazione a questo studio
2. precedente partecipazione allo studio ML18253
3. assunzione di almeno una dose di farmaco in studio durante lo studio ML18253

E.4

Principal exclusion criteria

Patients not satisfying the above inclusion criteria will not be enrolled in the study.

I pazienti che non soddisfano tutti i criteri di inclusione sopra elencati non saranno arruolati nello studio.

E.5 End points

E.5.1

Primary end point(s)

Association between IL28B genotypes at rs12979860 (CC vs. TC vs. TT) and rs8099917 (TT vs. GT vs. GG)and SVR (No vs. Yes) at EoF. SVR is defined as HBV DNA ≤ 2.000 UI/ml.

Correlazione tra i genotipi di IL28B [rs12979860 (CC vs. TC vs. TT) e rs8099917 (TT vs. GT vs. GG)]- e la SVR (No vs. Sì) a EoF. La SVR è definita come HBV DNA ≤ 2.000 UI/ml.

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

• Association between IL28B genotypes at rs12979860 (CC vs. TC vs. TT) and rs8099917 (TT vs. GT vs. GG) and SVR at EoT, defined as HBV DNA ≤ 2.000 UI/ml;
• Association between IL28B genotypes at rs12979860 (CC vs. TC vs. TT) and rs8099917 (TT vs. GT vs. GG) and HBsAg clearance, defined as HBsAg < 0.05 IU/ml, at EoT;
• Association between IL28B genotypes at rs12979860 (CC vs. TC vs. TT) and rs8099917 (TT vs. GT vs. GG) and HBsAg clearance, defined as HBsAg < 0.05 IU/ml, at EoF;
• Association between IL28B genotypes at rs12979860 (CC vs. TC vs. TT) and rs8099917 (TT vs. GT vs. GG) and HBsAg < 10 IU/ml at EoT;
• Association between IL28B genotypes at rs12979860 (CC vs. TC vs. TT) and rs8099917 (TT vs. GT vs. GG) and HBsAg < 10 IU/ml at EoF;
• Kinetic of HBsAg during treatment and follow-up by IL28B genotypes at rs12979860 (CC vs. TC vs. TT) and rs8099917 (TT vs. GT vs. GG).

• Correlazione tra i genotipi di IL28B [rs12979860 (CC vs. TC vs. TT) e rs8099917 (TT vs. GT vs. GG)] e la SVR a EoT, definita come HBV DNA ≤ 2.000 UI/ml;
• Correlazione tra i genotipi di IL28B [rs12979860 (CC vs. TC vs. TT) e rs8099917 (TT vs. GT vs. GG)] e l’eliminazione di HBsAg, definita come HBsAg < 0,05 UI/ml, a EoT;
• Correlazione tra genotipi di IL28B [rs12979860 (CC vs. TC vs. TT) e rs8099917 (TT vs. GT vs. GG)] e l’eliminazione di HBsAg, definita come HBsAg < 0,05 UI/ml, a EoF;
• Correlazione tra i genotipi di IL28B [rs12979860 (CC vs. TC vs. TT) e rs8099917 (TT vs. GT vs. GG)] e HBsAg < 10 UI/ml, a EoT;
• Correlazione tra i genotipi di IL28B [rs12979860 (CC vs. TC vs. TT) e rs8099917 (TT vs. GT vs. GG)] e HBsAg < 10 UI/ml, a EoF;
• Correlazione tra i genotipi di IL28B [rs12979860 (CC vs. TC vs. TT) e rs8099917 (TT vs. GT vs. GG)] e la cinetica di HBsAg durante il trattamento e il follow up.

E.5.2.1

Timepoint(s) of evaluation of this end point

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

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

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)

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

The end of the study is defined as last patient last phone follow-up, which is the date at which the last patient performs the follow-up for the assessment of adverse events related to study procedures.

La fine dello studio corrisponde all'ultima telefonata di follow up dell'ultimo paziente, ovvero la data in cui l'ultimo paziente viene sottoposto al follow up telefonico per la valutazione degli eventi avversi correlati alle procedure dello studio.

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

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:

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

112

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)

not applicable

non applicabile

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

2012-08-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-10

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

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IMP with orphan designation in the indication
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