A phase II, randomized, multicentre, observer-blind study to compare and characterize the immunoginicity and safety parameters induced by various GSK Biologicals’ Adjuvant Systems in combination with the Hepatitis B surface antigen (HBsAg), according to a 0, 1 month schedule with a booster at Month 12, in healthy, Hepatitis B virus (HBV) naïve, adults. - EARLY-CLINRES-002

• Register: EUCTR
• Last refreshed on: 11 August 2014
• Main ID: EUCTR2008-004455-29-BE
• Date of registration: 13/11/2008
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: A phase II, randomized, multicentre, observer-blind study to compare and characterize the immunoginicity and safety parameters induced by various GSK Biologicals’ Adjuvant Systems in combination with the Hepatitis B surface antigen (HBsAg), according to a 0, 1 month schedule with a booster at Month 12, in healthy, Hepatitis B virus (HBV) naïve, adults. - EARLY-CLINRES-002
• Scientific title: A phase II, randomized, multicentre, observer-blind study to compare and characterize the immunoginicity and safety parameters induced by various GSK Biologicals’ Adjuvant Systems in combination with the Hepatitis B surface antigen (HBsAg), according to a 0, 1 month schedule with a booster at Month 12, in healthy, Hepatitis B virus (HBV) naïve, adults. - EARLY-CLINRES-002
• Date of first enrolment: 05/12/2008
• Target sample size: 710
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004455-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Observer-blind If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium, Germany

Key inclusion & exclusion criteria

Inclusion criteria:
All Subjects must satisfy the following criteria at study entry :
•Subjects who the investigator believes that they can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study.
•A male or female between, and including, 18 and 45 years at the time of the first vaccination.
•Written informed consent obtained from the subject.
•Healthy subjects as established by medical history, clinical examination and clinical laboratory assessment before entering into the study.
•If the subject is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.

Adequate contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly (when applicable, as mentioned in the product label) for example abstinence, combined or progestogen oral contraceptives, injectable progestogen, implants of levonorgestrel, oestrogenic vaginal ring, percutaneous contraceptive patches or intrauterine device (IUD) or intrauterine system (IUS), vasectomy with documented azoospermia of the sole male partner or double barrier method (condom or occlusive cap plus spermicidal agent).

For azoospermia, “documented” refers to the outcome of the investigator's/designee’s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records.

Post-menopause: Menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential by ovarian failure. A practical definition accepts menopause after 1 year without menses with an appropriate clinical profile at the appropriate age e.g. > 45 years.

Are the trial subjects under 18? no
Number of subjects for this age range:
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) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Previous vaccination against Hepatitis B.
•Positive for anti-HBs antibodies, antiHBc antibodies, HBsAg, HCV antibodies and/or HIV.
•Any previous administration of MPL® and/or QS21.
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
•Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. (For corticosteroids, this will mean prednisone, or equivalent, >= 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
•Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine with the exception of the influenza vaccine which can be administered > 7 days preceding or > 7 days following each vaccine dose.
•Administration of immunoglobulins and/or any blood products within the last 3 months.
•Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
•History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
•Current serious neurologic or mental disease.
•Any past or current malignancies (excluding non-melanic skin cancer) and lymphoproliferative disorders.
•Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal functional abnormality, autoimmune disease or anemia as determined by physical examination or laboratory screening tests at the discretion of the investigator.
•Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral temperature <37.5°C.
•Pregnant or lactating female.
•History of chronic alcohol consumption and/or drug abuse.
•Other conditions that the principal investigator judges may interfere with study findings.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hepatitis B surface antigen (HBsAg) vaccine administred in HBV naïve adult subjects aged between 18 and 45 years old, inclusive, in good general health.

Intervention(s)

Product Name: HBsAg adjuvanted with AS01B
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: Recombinant Hepatitis B surface antigen
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 20-

Product Name: HBsAg adjuvanted with AS01E
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: Recombinant Hepatitis B surface antigen
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 20-

Product Name: HBsAg adjuvanted with AS03A
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: recombinant Hepatitis B surface antigen
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Engerix B
Product Name: Engerix B
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Recombinant Hepatitis B surface antigen
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Fendrix
Product Name: Fendrix
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Recombinant Hepatitis B surface antigen
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Product Name: HBsAg in adjuvant free solution
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Recombinant Hepatitis B surface antigen
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: To compare the magnitude of the cellular immune response, post dose 2 at Day 44, induced by various GSK Adjuvant Systems in combination with the HBsAg, in adult subjects aged between 18 and 45 years old, inclusive, in good general health and not previously immunized or previously infected with Hepatitis B.

Secondary Objective: •To compare the humoral immune response, post dose 2 at Day 60, induced by various GSK Adjuvant Systems in combination with HBsAg.
•To compare the kinetics of the cellular response induced by various GSK Adjuvant Systems in combination with HBsAg.
•To compare the kinetics of the humoral response induced by various GSK Adjuvant Systems in combination with HBsAg.
•To evaluate the innate immune response induced by various GSK Adjuvant Systems in combination with HBsAg.
•To evaluate potential correlation between cytokine/ chemokine response and reactogenicity induced by various GSK Adjuvant Systems in combination with HBsAg.
•To evaluate potential correlation between the innate and adaptive immune responses induced by various GSK Adjuvant Systems in combination with HBsAg.
•To evaluate safety and reactogenicity induced by various GSK Adjuvant Systems in combination with HBsAg throughout the entire study period.

Primary end point(s): Immunogenicity : Cellular immune response to components of the investigational vaccine 14 days post dose 2 (Day 44), in all subjects.

Secondary ID(s)

112115