Clinical Trials Register

Summary
EudraCT Number:	2013-001602-28
Sponsor's Protocol Code Number:	HXV02C
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:	2013-05-14
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

2013-001602-28

A.3

Full title of the trial

An open-label, controlled, multi-centre study of the immunogenicity and safety of a challenge dose of HBVAXPRO® to explore the anamnestic immune response in healthy children vaccinated 10 years ago with a primary series (3 doses) of either HEXAVAC® or INFANRIX®-HEXA

Uno Studio in aperto, controllato, multicentrico, sull’immunogenicità e sicurezza di una dose challenge di HBVAXPRO®, per valutare la risposta immunitaria anamnestica in bambini sani vaccinati 10 anni prima con una serie primaria (3 dosi) di HEXAVAC® o INFANRIX®-HEXA

A.3.1

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

study of the immunogenicity and safety of a decoy dose of HBVAXPRO®, in healthy children vaccinated 10 years ago with 3 doses of HEXAVAC® or INFANRIX®-HEXA.

studio sull'immunogenicità e sulla sicurezza della dose di richiamo con HBVAXPRO®, in bambini sani vaccinati 10 prima con 3 dosi di HEXAVAC® o INFANRIX®-HEXA.

A.3.2

Name or abbreviated title of the trial where available

HXV02C

A.4.1

Sponsor's protocol code number

HXV02C

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	Sanofi Pasteur MSD S.N.C.
B.1.3.4	Country	France
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	Sanofi Pasteur MSD SNC
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi Pasteur MSD SNC
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	8 rue Jonas Salk
B.5.3.2	Town/ city	Lyon cedex 07
B.5.3.3	Post code	69367
B.5.3.4	Country	France
B.5.4	Telephone number	+33(0)437282774
B.5.5	Fax number	+33(0)437284451
B.5.6	E-mail	sdard@spmsd.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	HBVAXPRO®
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur MSD S.N.C
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	Suspension for injection
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intramuscular use
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)	Yes
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	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

HEALTHY CHILDREN

BAMBINI SANI

E.1.1.1

Medical condition in easily understood language

HEALTHY CHILDREN

BAMBINI SANI

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

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 describe, in subjects vaccinated with 3 doses of HEXAVAC® as infants, the percentage of subjects with an anti-HBs concentration ≥10 mIU/mL one month after a challenge dose of HBVAXPRO® given at least 10 years later
*To describe, in subjects vaccinated with 3 doses of INFANRIX®-HEXA as infants, the percentage of subjects with an anti-HBs concentration ≥10 mIU/mL one month after a challenge dose of HBVAXPRO® given at least 10 years later

*Descrivere, nei soggetti vaccinati con tre dosi di HEXAVAC® in età infantile, la percentuale dei soggetti con una concentrazione di anti-HBs ≥10 mUI/mL un mese dopo la dose challenge di HBVAXPRO®, somministrata dopo un periodo di almeno 10 anni.
*Descrivere, nei soggetti vaccinati con tre dosi di INFANRIX®-HEXA in età infantile, la percentuale dei soggetti con una concentrazione di anti-HBs ≥10mUI/mL un mese dopo la dose challenge di HBVAXPRO®, somministrata almeno 10 anni dopo.

E.2.2

Secondary objectives of the trial

Immunogenicity objective:
*To describe, in subjects vaccinated with 3 doses of HEXAVAC® or 3 doses of INFANRIX®-HEXA as infants, the level of antibody to HBs before and one month after a challenge dose of HBVAXPRO® given at least 10 years later,
*To describe, in subjects vaccinated with 3 doses of HEXAVAC® or 3 doses of INFANRIX®-HEXA as infants, the level of antibody to HBs before and one month after a challenge dose of HBVAXPRO® given at least 10 years later, by subsets of subjects defined according to the pre-challenge anti-HBs concentration (<10 mIU/mL and ≥10 mIU/mL).
Safety objective:
*To describe the safety profile of HBVAXPRO®

Obiettivi di immunogenicità:
*Descrivere, nei soggetti vaccinati con tre dosi di HEXAVAC® o tre dosi di INFANRIX®-HEXA in età infantile, il livello di anticorpi anti-HBs prima e dopo un mese dalla challenge dose di HBVAXPRO®, somministrata dopo un periodo di almeno 10 anni.
*Descrivere, nei soggetti vaccinati con tre dosi di HEXAVAC® o tre dosi di INFANRIX®-HEXA in età infantile, il livello di anticorpi anti-HBs prima e dopo un mese dalla challenge dose HBVAXPRO®, somministrata dopo un periodo di almeno 10 anni, attraverso sottogruppi di soggetti definiti in base alla concentrazione pre-challenge di anti-HBs (<10 mUI/mL e ≥10 mUI/mL).
Obiettivo di sicurezza
*Descrivere il profilo di sicurezza di HBVAXPRO®.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects have to meet all the following criteria to be eligible for inclusion:
1.Healthy child of either gender
2.Child vaccinated with 3 doses of HEXAVAC® or 3 doses of INFANRIX®-HEXA as infants (documented vaccination history)
3.Child vaccinated with the third dose of HEXAVAC® or INFANRIX®-HEXA at least 10 years prior to challenge dose
4.Subject and parent(s) or legal representative fully understand study procedures, alternative treatments available, the risks involved with the study, and voluntarily agree to participate by giving written informed consent and assent.

I soggetti devono soddisfare tutti i seguenti criteri per risultare eleggibili:
1.Bambino sano, di entrambi i sessi.
2.Bambino vaccinato con tre dosi di HEXAVAC® o tre dosi di INFANRIX®-HEXA in età infantile (anamnesi vaccinale documentata).
3.Bambino vaccinato con la terza dose di HEXAVAC® o INFANRIX®-HEXA almeno 10 anni prima della dose challenge.
4.Il soggetto e i genitori o il tutore legale comprendono pienamente le procedure dello studio, le terapie alternative disponibili ed i rischi associati allo studio, a cui acconsentono volontariamente di partecipare fornendo il proprio consenso informato scritto ed assenso.

E.4

Principal exclusion criteria

Subjects meeting at least one of the following criteria will be ineligible for inclusion. Please note for criteria marked with an asterisk, a subject can return to be entered into the study once these criteria no longer apply:
1.*History of febrile illness (body temperature ≥38.0°C) in the 3 days prior to challenge dose
2.Receipt of more than 3 doses of any Hepatitis B containing vaccine either alone or in any combination
3.History of clinical diagnosis of infection due to Hepatitis B
4.History or current close contact with known carriers of Hepatitis B virus
5.Prior known sensitivity or allergy to any component of HBVAXPRO®
6.Known blood dyscrasias, leukemia, lymphomas of any type or other malignant neoplasms affecting the haematopoietic and lymphatic systems
7.Severe thrombocytopenia or other coagulation disorder that would contraindicate intramuscular injection
8.Immune impairment or humoral/cellular deficiency or depressed immunity
9.Subject is pregnant (as determined by a urine pregnancy test provided by the sponsor)
10.*High dose systemic corticosteroids (i.e. ≥ 1 mg/day/kg prednisone equivalent administered orally or parenterally) given ≥14 days in the 30 days prior to challenge dose. Inhaled, nasal or topical corticosteroids are not considered as systemic treatment
11.Immunoglobulins, blood or blood-derived products in the 3 months prior to challenge dose
12.*Inactivated vaccine in the 14 days prior to challenge dose
13.*Live vaccine in the 28 days prior to challenge dose
14.Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives
15.Subject that, in the investigator’s opinion, is likely to be lost to follow-up or to be poorly compliant with the study requirements
16.Planned participation in another clinical study during the present study period

I soggetti che soddisfano almeno uno dei seguenti criteri non saranno inclusi nello studio. Per i criteri contrassegnati con l’asterisco, il soggetto potrà essere incluso nello studio soltanto quando questi non saranno più applicabili:
1.* Storia di malattia febbrile (temperatura corporea ≥38,0 °C) nei 3 giorni che precedono la dose challenge.
2.Somministrazione di più di 3 dosi di un altro vaccino anti epatite B, da solo o in associazione.
3.Precedente diagnosi clinica d’infezione da epatite B.
4.Contatto ravvicinato, passato o recente, con portatori del virus dell’epatite B.
5.Nota sensibilità o allergia pregressa a qualsiasi componente di HBVAXPRO®.
6.Discrasia ematica documentata, leucemia, linfoma di qualsiasi tipo o altra neoplasia maligna che interessa il sistema ematopoietico e linfatico.
7.Trombocitopenia grave o altro disordine della coagulazione controindicati per l’iniezione intramuscolare.
8.Compromissione immunitaria o deficit umorale/cellulare o immunodeficienza.
9.Gravidanza del soggetto (determinata da un test sulle urine fornito dallo sponsor).
10.*Dosi elevate di corticosteroidi sistemici (per esempio ≥1 mg/die/kg in equivalenti di prednisone, somministrati per via orale o parenterale), somministrati per ≥14giorni nei 30 giorni che precedono la dose challenge. I corticosteroidi inalati o assunti per via nasale o topica non sono considerati trattamenti sistemici.
11.Immunoglobuline, sangue o emoderivati nei tre mesi che precedono la dose challenge.
12.*Vaccini inattivati nei 14 giorni precedenti la dose challenge.
13.*Vaccini vivi nei 28 giorni precedenti la dose challenge.
14.Qualsiasi condizione medica che, nell’opinione dello sperimentatore, possa interferire con la valutazione degli obiettivi dello studio.
15.Soggetto che, nell’opinione dello sperimentatore, rischia di non seguire o di essere scarsamente aderente ai requisiti dello studio.
16.Pianificata partecipazione ad un’altra sperimentazione clinica nel periodo del presente studio.

E.5 End points

E.5.1

Primary end point(s)

IMMUNOGENICITY
•Percentage of subjects with an anti-HBs concentration ≥10 mIU/mL before and one month after the challenge dose
•GMC before and one month after the challenge dose
•GMCR from before to one month after the challenge dose

IMMUNOGENICITÀ
•Percentuale di soggetti con una concentrazione di anti-HBs ≥10mUI/mL prima e dopo un mese dalla somministrazione della dose challenge.
•Media geometrica delle concentrazioni (GMC) prima e dopo un mese dalla somministrazione della dose challenge
•Media geometrica dei rapporti delle concentrazioni individuali anti HBs (GMCR) da prima fino a un mese dopo la somministrazione della dose challenge.

E.5.1.1

Timepoint(s) of evaluation of this end point

ONE MONTH

UN MESE

E.5.2

Secondary end point(s)

SAFETY
•From Day 0 to Day 4 percentage of subjects with solicited events:
oInjection-site adverse reactions (injection site erythema, injection site swelling and injection site pain),
oPyrexia defined as a body temperature ≥38.0°C
•From Day 0 to Day 14 percentage of subjects with:
oUnsolicited (i.e. spontaneously reported) injection-site adverse reactions,
oUnsolicited (i.e. spontaneously reported) systemic adverse events,
•From study vaccination to the last visit: percentage of subjects with serious adverse events

SICUREZZA
•Dal Giorno 0 al Giorno 4, percentuale di soggetti con eventi sollecitati:
oReazioni avverse nel sito di iniezione (eritema, gonfiore e dolore in corrispondenza del sito di iniezione);
oPiressia, definita come temperatura corporea ≥38,0 °C.
•Dal Giorno 0 al Giorno 14, percentuale di soggetti con:
oReazioni avverse non sollecitate (ossia descritte spontaneamente) nel sito d’iniezione;
oEventi avversi sistemici non sollecitati (ossia descritti spontaneamente)
•Dalla vaccinazione all’ultima visita: percentuale di soggetti con eventi avversi seri.

E.5.2.1

Timepoint(s) of evaluation of this end point

ONE MONTH

UN MESE

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

Yes

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

IMMUNOGENICITY

IMMUNOGENICITA'

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

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

il controllo è riferito al trattamento effettuato dai pazienti prima dell'inizio dello studio

the comparator is referred to the treatment before the start of the this study

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 WILL BE DEFINED AS THE END OF DATA COLLECTION INCLUDING AVAILABILITY OF SEROLOGY RESULTS

LA FINE DELLO STUDIO SARA' DEFINITA COME LA FINE DELLA RACCOLTA DATI INCLUSI I RISULTATI DISPONIBILI DI SIERIOLOGIA

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

Yes

F.1.1

Number of subjects for this age range:

750

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:

375

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

375

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

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

750

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)

NONE

NESSUNO

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

2013-07-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-02-04

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