Clinical Trials Register

Summary
EudraCT Number:	2012-001344-22
Sponsor's Protocol Code Number:	116640
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-01-16
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-001344-22

A.3

Full title of the trial

A phase II, randomised, single-blind study to develop read-outs aimed at detecting and characterising the early and adaptive immune responses and to evaluate the kinetics of the early response and reactogenicity in healthy, hepatitis B virus naive adults vaccinated with the hepatitis B surface antigen in combination with a GSK Biologicals’ Adjuvant System

A.3.1

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

Development of read-outs in healthy, hepatitis B virus naive adults vaccinated with the hepatitis B surface antigen (HBsAg) in combination with a GlaxoSmithKline (GSK) Biologicals’ Adjuvant System.

A.3.2

Name or abbreviated title of the trial where available

EARLY-CLINRES-008

A.4.1

Sponsor's protocol code number

116640

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.4.1	Name of organisation providing support	Region Wallonne
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	Institute for Medical Immunology (Université Libre de Bruxelles)
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	Clincical 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	No
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.3.1	Product name	Hepatitis B surface antigen (HBsAg) candidate vaccine adjuvanted with AS01B
D.3.4	Pharmaceutical form	Powder and solvent for 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	HEPATITIS B SURFACE ANTIGEN
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/ml microgram(s)/millilitre
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	ENGERIX-B
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Biologicals
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.3.1	Product name	Engerix-B
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HEPATITIS B SURFACE ANTIGEN
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/ml microgram(s)/millilitre
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.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Healthy volunteers (Hepatitis B surface antigen (HBsAg) vaccine administered in hepatitis B virus (HBV) naive adult subjects aged between 18 and 45 years old, inclusive, in good general health.)

E.1.1.1

Medical condition in easily understood language

Infections caused by the hepatitis B virus

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 detect and measure soluble mediators from the early immune response in plasma.

E.2.2

Secondary objectives of the trial

•To evaluate the antibody response induced by GSK Biologicals’ adjuvanted investigational vaccine or by Engerix-B.
•To evaluate the magnitude of the T-cell immune response induced by GSK Biologicals’ adjuvanted investigational vaccine or by Engerix-B.
•To evaluate and further characterise the reactogenicity and its kinetics following the administration of GSK Biologicals’ adjuvanted investigational vaccine or of Engerix-B.
•To evaluate the safety following the administration of GSK Biologicals’ adjuvanted investigational vaccine or of Engerix-B.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
•A male or female between, and including, 18 and 45 years of age at the time of first study product administration.
•Written informed consent obtained from the subject.
•Healthy subjects, in the opinion of the investigator, as established by medical history, clinical examination, and clinical laboratory assessment with no active disease that could interfere with the study endpoints, before entering into the study.
•Body Mass Index (BMI) between 18.5 and 30 kg/m2.
•Female subjects of non-childbearing potential may be enrolled in the study
-Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
•Female subjects of childbearing potential may be enrolled in the study, if the subject:
-has practiced adequate contraception for 30 days prior to first study product administration , and
-has a negative pregnancy test on the day of placebo administration/ vaccination, and
-has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study.

E.4

Principal exclusion criteria

•Known history of HBV infection.
•Previous vaccination against hepatitis B.
•Positive for anti-hepatitis B surface (HBs) antibodies, anti-hepatitis B core (HBc) antibodies, HBsAg, HCV antibodies and/or HIV.
•Any previous administration of vaccine components.
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first study product administration , or planned use during the study period.
•No significant dietary restrictions or life-threatening food allergies.
•Regular use of non steroidal anti-inflammatory drugs within 1 month prior to first study product administration .
•Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first study product administration. Inhaled and topical steroids are allowed.
•Planned administration / administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first study product administration and during the entire study period(both Steps), with the exception of the influenza vaccine (pandemic or seasonal) which can be administered > 21 days preceding or > 21 days following each placebo/vaccine administration.
•Administration of immunoglobulins and/or any blood products within the last 3 months preceding the first study product administration or planned administration during the study period.
•Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV based on screening evaluations and on medical history and physical examination.
•History of or current bleeding or coagulation disorder.
•Any known or clinical signs of anaemia or any clinical condition (including vascular disorder) that would preclude frequent blood drawings.
•Poor venous access as assessed at screening by the investigator.
•Blood loss, including blood donation, of more than 300 mL within 90 days before the first study product administration .
•History of or current autoimmune or other immune-mediated disease.
•Any haematological or biochemical level out of normal range before entering into the study, as follows:
-Haemoglobin level < lower normal limit (LNL).
-Platelet counts out of normal range.
-Alanine aminotransferase [ALT] > upper normal limit (UNL).
-Aspartate aminotransferase [AST] > UNL.
-Creatinine > UNL.
-c-reactive protein [CRP] > UNL.
-Creatine phosphokinase [CPK] > UNL without any plausible explanation for this abnormality (such as sport activity).
In case of haematological and/or biochemical value out of range for parameters mentioned here above, one re-testing of out of range value may be performed.
•Any acute or chronic, clinically significant disease, as determined by medical history, physical examination or laboratory screening tests.
•Known or suspected reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
•Acute disease and/or fever at the time of enrolment.
-Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
-Fever is defined as temperature ≥ 37.5°C for oral route.
•Pregnant or lactating female.
•Recent history of chronic alcohol consumption and/or drug abuse.
•Other conditions that the principal investigator judges may interfere with study findings.

E.5 End points

E.5.1

Primary end point(s)

Innate/early immune response: Soluble mediators from the innate/early immune response in all subjects (Step 1 and Step 2).

E.5.1.1

Timepoint(s) of evaluation of this end point

Day of study product administration (D-30 [step 1 only], D0 [both steps], D30 [step 1 & Group C in step 2], D180 [Group D in step 2 only]) and, during a maximum of 7 day follow-up period post study product administration.

E.5.2

Secondary end point(s)

-Adaptive response: Classical cellular and humoral immune response to components of the study vaccine.
-Occurrence of solicited and non-serious unsolicited adverse events (AEs) (Step 1 and 2).
-Occurrence of any serious adverse event (SAE) (Step 1 and 2).
-Occurrence of any Potential Immune-Mediated Disease (pIMD) (Step 1 and 2).
-Occurrence of any new medical condition requiring medical attention (Step 1 and 2).
-Safety laboratory parameters (Step 1 and 2).
-Vital signs (Step 1 and 2).

E.5.2.1

Timepoint(s) of evaluation of this end point

Adaptive response: D0, D44, D60, D180, D210 (Step1) - D0, D44 (GroupC) - D0, D194 (GroupD-Step2)
Solicited and unsolicited AEs: Day of study product administration (D-30 [step1], D0 and D30 [both Steps], D180 [GroupD-Step 2]) and during a max of 28 day FU period post study product administration
Occurrence of any SAE & pIMD: Entire study period
New medical condition requiring medical attention: Entire study period
Safety laboratory parameters: At D0, D1, D7, D30, D31, D37, D60 (Step1) - D0, D2, D30, D31, D32, D37, D60 (GroupC) - D0, D2, D180, D181, D182, D187, D210 (GroupD-Step2)
Vital signs: Day of study product administration (D-30 [step1], D0 [both steps], D30 [Step1 & GroupC-Step2] and D180 (GroupD-Step2) and, during a max of 30 day FU period post study product administration

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

This trial will be conducted in 2 steps. Each step will contain 2 parallel arms.

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

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

LSLV

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.1.1.1

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)

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.4.1

In the member state

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

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2016-09-13

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