Clinical Trials Register

Summary
EudraCT Number:	2004-000558-22
Sponsor's Protocol Code Number:	P02538
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:	2005-09-26
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

2004-000558-22

A.3

Full title of the trial

Assessment of the safety, efficacy, tolerability and pharmacokinetics of PegIntron plus Rebetol in pediatric patients with chronic hepatitis C.

Valutazione di sicurezza, efficacia, tollerabilita` e farmacocinetica di PegIntron + Rebetol in pazienti pediatrici affetti da Epatite C.

A.3.1

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

Assessment of the safety, efficacy, tolerability and pharmacokinetics of PegIntron plus Rebetol in pediatric patients with chronic hepatitis C.

Valutazione di sicurezza, efficacia, tollerabilita` e farmacocinetica di PegIntron + Rebetol in pazienti pediatrici affetti da Epatite C.

A.4.1

Sponsor's protocol code number

P02538

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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4	Country	United States
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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., 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	MSD Italia s.r.l.
B.5.2	Functional name of contact point	Divisione Ricerca Clinica
B.5.3	Address:
B.5.3.1	Street Address	Via Fratelli Cervi, Centro Direzionale Milano Due, Palazzo Borromini
B.5.3.2	Town/ city	Segrate
B.5.3.3	Post code	20090
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39 02 21018402
B.5.5	Fax number	+39 02 21018629
B.5.6	E-mail	gcto.italy@merck.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	PEGINTRON*SC 1FL 100MCG+1F
D.2.1.1.2	Name of the Marketing Authorisation holder	SP EUROPE
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	Powder and solvent for 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-2b
D.3.9.1	CAS number	215647-85-1
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.3	Concentration number	100
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	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	Non Applicabile
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	REBETOL*84CPS 200MG
D.2.1.1.2	Name of the Marketing Authorisation holder	SP EUROPE
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, hard
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.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile
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	Rebetol
D.2.1.1.2	Name of the Marketing Authorisation holder	SP EUROPE
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	Syrup
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.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	40
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	Non Applicabile

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 in pediatric patients.

Epatite cronica C in pazienti pediatrici

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis C

epatite cronica 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	10019744
E.1.2	Term	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

To assess the safety, efficacy and tolerability of the combination of PEG-Intron 60 μg/m2 once weekly (QW) plus REBETOL 15 mg/kg/day in pediatric subjects with chronic hepatitis C.

Valutare sicurezza, efficacia e tollerabilita' della combinazione di PegIntron 60 mcg/m2 una volta alla settimana (QW) + Rebetol 15 mg/kg/die in pazienti pediatrici affetti da epatite C.

E.2.2

Secondary objectives of the trial

To measure the multiple-dose pharmacokinetics of PEG-Intron and REBETOL in pediatric subjects with chronic hepatitis C.

Verificare i parametri farmacocinetici dopo somministrazioni ripetute di PegIntron e Rebetol in pazienti pediatrici con epatite cronica C.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:1
Date:2004/06/02
Title:Assessment of the Safety, Efficacy, Tolerability, and Pharmacokinetics of PEG-Intron Plus REBETOL in Pediatric Patients With Chronic Hepatitis C
Objectives:To measure the multiple-dose pharmacokinetics of PEG-Intron and REBETOL in pediatric subjects with chronic hepatitis C.

OTHER SUBSTUDIES:
Tanner staging (optional) to assess sexula organ development

FARMACOCINETICA/FARMACODINAMICA:
Vers:1
Data:2004/06/02
Titolo:valutazione di sicurezza, efficacia, tollerabilita` e farmacocinetica di Peg Intron + Rebetol in pazienti pediatrici affetti da Epatite C cronica
Obiettivi:verificare i parametri farmacocinetici dopo somministrazioni ripetute di Peg Intron e rebetol in pazienti pediatrici con epatite cronica C

ALTRI SOTTOSTUDI:
stadiazione di Tanner (opzionale) per valutare lo sviluppo degli organi sessuali

E.3

Principal inclusion criteria

Informed consent must be obtained from subject’s parent or legal guardian prior to any study-related procedures and the subject must be able to adhere to the dose and visit schedule. According to local laws and/or IRB/IEC requirements, subjects may also need to provide written assent. 2. History of chronic hepatitis C as documented either by anti-HCV or HCV RNA positivity at least 6 months prior to Screening 1. 3. Subjects 3 through 17 years of age (inclusive) at time of Screening 2, of either gender. 4. Body weight ≤90 kg at the Screening 2 visit. In addition, subjects undergoing pharmacokinetic sampling must weigh ≥13 kg at the Screening 2 visit. 5. Plasma positive for HCV RNA by quantitative RT-PCR, as measured by the sponsor`s assay, during Screening 1 visit. 6. Results of a liver biopsy performed prior to entry to the study are required

1. ottenimento del consenso informato 2. storia di epatite cronica C documentata tramite anti-HCV o HCV RNA positivo nei 6 mesi precedenti lo screening 1 3. pazienti di eta` compresa tra i 3 e i 17 anni al momento dello screening 2, di ambo i sessi 4. peso <= 90 kg allo screening 2

E.4

Principal exclusion criteria

1. Serum ALT level >10 times the upper limit of normal within the 6 months prior to Screening 1 visit. 2. Any other cause for liver disease other than chronic hepatitis C. 3.Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices or hepatic encephalopathy. 4. The most recent liver biopsy is normal, as determined by the local pathology report. 5. Prior treatment for chronic hepatitis C, including but not limited to antiviral or immunomodulatory product, any interferon product, or ribavirin, either as monotherapy or in combination. 6. Suspected hypersensitivity to any interferon product or ribavirin. 7. Known coinfection with either HIV or HBV. 8. Known immunodeficiency disorders requiring immunoglobulin therapy. 9. Known coagulopathies, including hemophilia, or anticoagulant use. 10. Known hemoglobinopathies. 11. Known G6PD deficiency. 12. Evidence of active or suspected malignancy, or a history of malignancy within the last 5 years. 13. Subjects with organ transplants.

1. ALT > 10 X UNL nei 6 mesi precedenti la V1 2. altre patologie epatiche, oltre l`epatite C 3. la biopsia piu` recente e` normale 4. precedente trattamento per epatite C

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint(s) are the safety and efficacy (efficacy defined as the proportion of subjects in each group that exhibits SVR at 24 weeks of follow-up) of PEG-Intron and REBETOL.

Valutazione di sicurezza ed efficacia [quest'ultima definita come la proporzione di soggetti per gruppo che dimostra una risposta virologica mantenuta alla settimana 24 di follow-up] di PegIntron e Rebetol.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 settimana di follow-up

E.5.2

Secondary end point(s)

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

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

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

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

Argentina

Puerto Rico

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

LVLS

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

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

minor

minori

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

100

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)

follow-up

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

2005-06-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-04-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-01-10

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