Clinical Trials Register

Summary
EudraCT Number:	2015-001517-27
Sponsor's Protocol Code Number:	208127/084,100566/567/568/569/570
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-06-03
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

2015-001517-27

A.3

Full title of the trial

An open multicentre, multicountry study to evaluate long-term anti-body persistence and immune memory between Years 11 and 15 after the primary study HAB-084 in which healthy adolescents were vaccinated with Twinrix™ Adult following a two-dose schedule or Twinrix™ Junior following a three-dose schedule.

A.3.1

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

Study to compare the immunogenicity, safety and reactogenicity of SmithKline Beecham’s Twinrix administered following a 2 dose schedule (0, 6 months) to that of Twinrix Junior administered following a 3 dose schedule (0, 1, 6 months) in healthy volunteers aged 12-15 years.

A.3.2

Name or abbreviated title of the trial where available

HAB-084, HAB-153EXT:084Y6, HAB-154EXT:084Y7, HAB-155EXT:084Y8, HAB-156EXT:084Y9, HAB-157EXT:084Y10

A.4.1

Sponsor's protocol code number

208127/084,100566/567/568/569/570

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.3.4	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 enzyme-linked immunosorbent assay unit
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.3.4	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 enzyme-linked immunosorbent assay unit
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	360
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.3.11 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

To protect healthy volunteers between the ages of 12 and 15 years against hepatitis A and hepatitis B viruses and to determine the optimal dose range and schedule of the combined hepatitis A / hepatitis B vaccine, with respect to immunogenicity, reactogenicity and safety in this age group.

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 primary study:
To demonstrate, that the immunogenicity elicited by the combined hepatitis A / hepatitis B vaccine Twin-rix is at least equivalent to that of Twinrix Junior vaccine, by measuring the anti-HAV and anti-HBs antibody levels reached at month 7.
For the long term follow-up (LTFU):
To evaluate anti-HAV and anti-HBs antibody per-sistence at Year 6 (i.e. Month 72), Year 7 (i.e. Month 84), Year 8 (i.e. Month 96), Year 9 (i.e. Month108) and Year 10 (i.e. Month 120) after the first vaccine dose of the two-dose or three-dose primary vaccination.

E.2.2

Secondary objectives of the trial

To compare the immunogenicity elicited by the combined hepatitis A / hepatitis B vaccine Twinrix to that of the Twinrix Junior vaccine by measuring the anti-HAV and anti-HBs antibody levels reached at months 1, 2, and 6.
To compare the safety and reactogenicity of the combined hepatitis A / hepatitis B vaccine Twinrix to that of Twinrix Junior vaccine after each vaccine dose.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For primary study:
Healthy male and female volunteers between the ages of 12-15 years at first vaccination will be enrolled in this study.
Negative titres for anti-HAV, anti-HBs, anti-HBc antibodies and / or HBsAg.
Age: between 12 and 15 years at the time of the first vaccination.
Free of obvious health problems as established by medical history and clinical examination before entering into the study.
Written informed consent obtained from the parent / guardian of the subject.
If the subject is female, she must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions.
For the LTFU:
Subjects who had received at least one dose of the study vaccine in the primary study HAB-084.
Written informed consent was obtained from each subject or parent/guardian of the subject before the first blood-sampling visit of the follow-up.

E.4

Principal exclusion criteria

Use of any investigational or non-registered drug or vac-cine other than the study vaccines during the study period or within 30 days preceding the first dose of study vaccine.
Administration of chronic immunosuppressants or other immune-modifying drugs within six months.
Planned administration of a vaccine not foreseen by the study protocol during the period starting from one week before each dose of vaccine and ending 30 days after.
Previous vaccination against hepatitis A or hepatitis B.
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection.
Family history of congenital or hereditary immunodeficiency
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
Major congenital defects or serious chronic illness.
History of any neurologic disorders or seizures.
Acute disease at the time of enrollment.
Hepatomegaly, right upper quadrant abdominal pain or tenderness.
Oral or axillary temperature of >= 37.5° C.
Administration of immunoglobulin and / or any blood product within the six months preceding the first dose of study vaccine or planned administration during the study period.
Pregnant or lactating female.

E.5 End points

E.5.1

Primary end point(s)

Titres for anti-Hepatitis A virus (HAV) antibodies and for anti-Hepatitis B surface antigen (HBs) antibodies.
For the LTFU:
Anti-HAV seropositivity rates and GMCs (calculated on ser positive subjects).
Anti-HBs seropositivity rates, proportion of 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 endpoint: At Month 7
For LTFU endpoints: At all the LTFU points (At Years 6, 7, 8, 9 and 10).

E.5.2

Secondary end point(s)

Titres for anti-HAV and anti-HBs antibodies.
Reactogenicity after each dose (defined as solicited adverse events [AEs], unsolicited adverse events and serious adverse events [SAEs} reported).
For the LTFU:
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 anti-HAV and anti-HBs antibodies titres: At month 1, 2, and 6.
For solicited AEs-reported on the day of vaccination (Day 0) and during the three-day follow-up period after each vaccine dose (Day 0 to Day 3).
For unsolicited AEs-Occurring within 30 days after each vaccine dose (Day 0 to Day 30).
For SAEs-During the course of the study (Month 0 to Month7).
For SAEs in LTFU: At all the LTFU time-points (At Years 6, 7, 8, 9 and 10).

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

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

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

Yes

E.8.6.3

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

Belgium

Czech Republic

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:

300

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

300

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

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.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

300

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:	Belgium

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