Challenge Dose of Hepatitis B Vaccine in Subjects Who Previously Received Engerix™-B Vaccine

Study Overview
=================
Brief Summary
-----------------
To evaluate the response to an additional dose (challenge dose) of hepatitis B vaccine, when given to subjects who had received primary vaccination of Engerix™-B vaccine approximately 72-78 months ago. This protocol posting deals with objectives & outcome measures of the challenge phase. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
-----------------
Administration of a Challenge Dose of Hepatitis B Vaccine in Subjects Who Previously Received Engerix™-B Vaccine.

Conditions
-----------------
Hepatitis B

Intervention / Treatment
-----------------
* Biological: Engerix™-B


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol. A male or female who had received complete primary vaccination course of hepatitis B vaccine in the primary study Written informed consent obtained from the subject and/or parent/guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. If the subject is female, she must be of non-childbearing potential 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 the hepatitis B challenge dose. Exclusion Criteria: Use of any investigational/non-registered drug or vaccine other than the study vaccine within 30 days preceding the hepatitis B vaccine challenge dose or planned use during the study period. Chronic administration (more than 14 days) of immunosuppressants other immune-modifying drugs within six months prior to the hepatitis B vaccine challenge dose. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before the hepatitis B vaccine challenge dose and ending 30 days after. Subjects who received an additional dose of hepatitis B vaccine outside the context of the study between the primary vaccination course and the hepatitis B challenge vaccination visit. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Acute disease at the time of enrolment. Acute or chronic, clinically significant hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Administration of immunoglobulins and/or any blood products within the three months preceding the hepatitis B vaccine challenge dose or planned administration during the study period (one month). Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions.

Ages Eligible for Study
-----------------
Minimum Age: 17 Years
Maximum Age: 22 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Engerix 2 Doses + Challenge Dose<br>Subjects received 2 doses of Engerix™-B (Month 0 and 6) in the primary study and a single dose of Engerix™-B during the booster study. | Biological: Engerix™-B<br>* One dose (10µg Hepatitis B surface antigen (HBsAg))<br>* Other names: Hepatitis B vaccine;|
| Experimental: Engerix 3 Doses + Challenge Dose<br>Subjects received 3 doses of Engerix™-B (Month 0, 1 and 6) in the primary study and a single dose of Engerix™-B during the booster study. | Biological: Engerix™-B<br>* One dose (10µg Hepatitis B surface antigen (HBsAg))<br>* Other names: Hepatitis B vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Immunological Response to Challenge Dose in Terms of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Immune response defined as: For initially seronegative subjects (anti-HBs antibody concentration <3.3 milli-international unit per milliliter [mIU/mL] before vaccination) antibody concentration ≥ 10mIU/mL at post booster. For initially seropositive subjects: antibody concentration at post booster ≥ 4-fold the pre-vaccination antibody concentration. | 30 days post-challenge dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Anti-HBs Antibody Concentrations Above the Cut-off Value | Anti-HBs antibody cut-off values assessed include 3.3, 10 and 100 mIU/mL. | 30 days post-challenge dose | 
| Concentration of Anti-HBs Antibodies | Concentrations given as geometric mean concentration (GMC) and expressed in mIU/mL. | 30 days post-challenge dose | 
| Number of Participants Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. | During the 4-day follow-up period (Day 0-3) after the challenge dose | 
| Number of Participants Reporting Solicited General Symptoms | Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms, and headache. | During the 4-day follow-up period (Day 0-3) after the challenge dose | 
| Number of Participants Reporting Unsolicited Adverse Events (AE) | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | During the 31-day follow-up period (Day 0-30) after the challenge dose | 
| Number of Participants Reporting Serious Adverse Events (SAE) | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | During the 31-day follow-up period (Day 0-30) after the challenge dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis B, Persistence, Challenge dose