Clinical Trials Register

Summary
EudraCT Number:	2015-001515-12
Sponsor's Protocol Code Number:	208127/120,/132,/133,/134,/137
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-06-24
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2015-001515-12

A.3

Full title of the trial

A phase III, open, randomized, multicentre, multicountry study to compare the reactogenicity and evaluate the safety and immunogenicity of GSK Bio’s combined hepatitis A / hepatitis B vaccine (at least 720 EL.U of hepatitis A antigen and 20 µg of hepatitis B surface antigen per dose of 1 ml) administered according to a 0, 6 month schedule by intramuscular injection versus Twinrix™ Junior (at least 360 EL.U of hepatitis A antigen and 10 µg of hepatitis B surface antigen per dose of 0.5 ml) administered according to a 0, 1, 6 month schedule by intramuscular injection in healthy children between 1 to 11 years old.

A.3.1

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

Study to compare the reactogenicity and evaluate the safety and immunogenicity of GSK Biologicals combined hepatitis A / hepatitis B vaccine administered according to a 0, 6 month schedule versus Twinrix™ Junior administered according to a 0, 1, 6 month schedule in healthy children between 1 to 11 years old.

A.3.2

Name or abbreviated title of the trial where available

HAB-120, HAB-132 EXT HAB 120Y2, HAB-133 EXT HAB 120Y3, HAB-134 EXT HAB 120Y4, HAB-137 EXT HAB 120Y5

A.4.1

Sponsor's protocol code number

208127/120,/132,/133,/134,/137

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	GlaxoSmithKline Biologicals
B.1.3.4	Country	Belgium
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	GlaxoSmithKline Biologicals
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Biologicals
B.5.2	Functional name of contact point	Clinical Disclosure Advisor
B.5.3	Address:
B.5.3.1	Street Address	Rue de l’Institut, 89
B.5.3.2	Town/ city	Rixensart
B.5.3.3	Post code	1330
B.5.3.4	Country	Belgium
B.5.4	Telephone number	442089904466
B.5.6	E-mail	GSKClinicalSupportHD@gsk.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	Twinrix Adult
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Biologicals SA
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.3.2	Product code	HAB Adult
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.2	Current sponsor code	HAV
D.3.9.3	Other descriptive name	HEPATITIS A VIRUS (INACTIVATED)
D.3.9.4	EV Substance Code	SUB20081
D.3.10	Strength
D.3.10.1	Concentration unit	ELISA unit/dose enzyme-linked immunosorbent assay unit/dose
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	720
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.2	Current sponsor code	HBsAg
D.3.9.3	Other descriptive name	HEPATITIS B SURFACE ANTIGEN
D.3.9.4	EV Substance Code	SUB14083MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Twinrix Paediatric
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Biologicals SA
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.3.2	Product code	HAB Ped
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.2	Current sponsor code	HBsAg
D.3.9.3	Other descriptive name	HEPATITIS B SURFACE ANTIGEN
D.3.9.4	EV Substance Code	SUB14083MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.2	Current sponsor code	HAV
D.3.9.3	Other descriptive name	HEPATITIS A VIRUS (INACTIVATED)
D.3.9.4	EV Substance Code	SUB20081
D.3.10	Strength
D.3.10.1	Concentration unit	ELISA unit/dose enzyme-linked immunosorbent assay unit/dose
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	360
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

Vaccination of healthy children from 1 to 11 years old against Hepatitis

E.1.1.1

Medical condition in easily understood language

Infection of the liver
Persistent Jaundice
Liver failure
Liver cancer

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

For the primary study:
To demonstrate that the combined hepatitis A / hepatitis B (720/20) vaccine is not more reactogenic than Twinrix™ Junior.

For the long term follow up (LTFU):
To evaluate anti-HAV and anti-HBs antibody persistence at Year 2, Year 3, Year 4 and Year 5 after the first vaccine dose of the primary vaccination course (a two-dose schedule of Twinrix Adult 720/20 vaccine or a three-dose schedule of Twinrix Junior 360/10 vaccine).
To evaluate the immune memory in the subjects who became seronegative for anti-HAV antibodies (i.e. anti-HAV antibody concentrations < 15 mIU/ml) or had anti-HBs antibody concentrations < 10 mIU/ml at the long-term blood sampling time-point (i.e. Year 2, 3, 4 or 5) and who received the challenge dose (administered 6 to 12 months after the Year 5 time-point).

E.2.2

Secondary objectives of the trial

To assess the reactogenicity after each vaccine dose.
To assess the safety throughout the study.
To evaluate the immunogenicity elicited by the study vaccines, by measuring the anti-Hepatitis A virus (HAV) and anti-Hepatitis B surface antigen (HBs) antibody levels reached one month following the last vaccine dose (month 7).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Fro the primary study:
A male or female between, and including, 1 and 11 years of age at the time of the first vaccination.
Written informed consent obtained from the parent or guardian of the subject and/or the subject.
Free of obvious health problems as established by medical history and clinical examination before entering into the study.
Not known to be seropositive for anti-HAV antibodies, HBs antigen, anti-HBc and anti-HBs antibodies.
Although very unlikely in this age group, female partici-pants who may be at risk of becoming pregnant should take precautions to avoid pregnancy.

For the LTFU:
Subjects who had received at least one dose of the study vaccine in the primary study HAB-120.
Written informed consent was obtained from the parents or guardians of the subject before the blood-sampling visit of each follow-up visit.

E.4

Principal exclusion criteria

Use of any investigational or non-registered drug or vac-cine other than the study vaccines within 30 days preced-ing the first dose of study vaccine, or planned use during the study period.
Any chronic drug therapy to be continued during the study period.
Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccines.
Previous vaccination against hepatitis A or B.
History of hepatitis A or B.
Any confirmed or suspected immunosuppressive or im-munodeficient condition, including human immunodefi-ciency virus infection.
History of allergic disease or reactions likely to be exac-erbated by any component of the vaccine.
History of any neurologic disorders or seizures.
Acute disease at the time of enrolment.
Hepatomegaly, right upper quadrant abdominal pain or tenderness.
Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

E.5 End points

E.5.1

Primary end point(s)

Overall number of subjects reporting with at least one grade 3 solicited symptom.
For the LTFU:
Anti-HAV seropositivity rates and geometric mean concentrations (GMCs) (calculated on seropositive subjects).
Anti-HBs seropositivity rates, proportion of the subjects with antibody concentrations >=10 mIU/ml and GMCs (calculated on seropositive subjects).

E.5.1.1

Timepoint(s) of evaluation of this end point

For primary study: On the day of vaccination (Day 0) and during the 3 day follow-up period after each vaccine dose (Day 0-3).
For LTFU: At all the LTFU time-points (at Years 2, 3, 4 and 5).

E.5.2

Secondary end point(s)

Frequency and intensity of local solicited symptoms.
Frequency, intensity and relationship of general solicited symptoms.
Frequency, intensity and relationship of unsolicited symptoms.
Frequency, intensity and relationship of serious adverse events (SAEs).

For LTFU :
Anti-Hepatitis A virus (HAV) and anti-Hepatitis B surface antigen (HBs) antibody titres.
Seroconversion rate (SC) and geometric mean titres (GMTs) for anti-HAV antibodies.
SC rate, seroprotection (SP) and GMTs for anti-HBs antibodies.
SAEs that are determined by the investigator to have a causal relationship to primary vaccination, any event related to a lack of vaccine efficacy (i. e. hepatitis A or hepatitis B infection), SAEs that are related to study participation (blood sampling).

E.5.2.1

Timepoint(s) of evaluation of this end point

For solicited local and general symptoms: On the day of vaccination (Day 0) and during the 3 day follow-up period after each vaccine dose (Day0-3).
For unsolicited symptoms: Within 30 days after each vaccine dose and overall.
For SAEs: During the study up to 30 days after the last vaccination.
For anti-HAV and anti-HBs antibody titres at LTFU time point: At Month 0 and Month 7 for all subjects.
For seroprotection, seroconversion and GMTs at LTFU time point: At Month 7 for all subjects.
For SAEs at LTFU time points : At all the LTFU time-points (at Years 2, 3, 4 and 5).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

reactogenicity, immunology

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Australia

Belgium

Spain

Sweden

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

LVLS

E.8.9 Initial estimate of the duration of the trial

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:

511

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

100

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

411

F.1.1.6

Adolescents (12-17 years)

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.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

511

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

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Australia

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