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.) |
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E.1.1.1 | Medical condition in easily understood language |
Infections caused by the hepatitis B virus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
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. |
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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.
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E.2.3 | Trial contains a sub-study | No |
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.
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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.
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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). |
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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. |
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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). |
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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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
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. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 21 |