Evaluation of Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™

GlaxoSmithKline210 enrolled

Overview

This study will evaluate the immune response against Hepatitis-A (HAV) and Hepatitis B surface (HBs) antigen in healthy subjects aged 12 to 15 years (at the time of primary vaccination), who received vaccination course with GSK Biologicals' Twinrix Adult and Twinrix Junior vaccine, approximately 10 years ago in the primary study. The subjects will be invited for blood sampling at 11, 12, 13, 14 and 15 years after primary vaccination to evaluate the persistence of immune response. For subjects detected with decreased immunity, the presence of immune memory against hepatitis A \& B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine 6 to 12 months after the Year 15 follow-up time-point. No new subjects will be recruited during this booster phase of the study.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

210

Conditions

Hepatitis B Hepatitis A

Interventions

Additional challenge doseBIOLOGICAL

If a subject became seronegative for anti-HAV antibodies (\< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 15 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study * Written informed consent obtained from the subject. All subjects must satisfy the following criteria at entry into the challenge dose phase: * A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study. * Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points. * Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * Written informed consent obtained from the subject. * Healthy subjects as established by medical history and clinical examination before entering into the challenge dose phase of this study. * If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination. Exclusion Criteria: The following criteria should be checked at each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit. * Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit. * Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study. * History of hepatitis A or hepatitis B infection. * Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 months prior to blood sampling. The following criteria should be checked before the challenge dose phase. If any apply, the subject must not be included in the challenge dose phase: * Use of any investigational or non-registered product (drug or vaccine) within 30 days before the administration of the challenge dose or planned use during the study period outside the context of the study. * Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine between the primary vaccination course of the primary study and the challenge dose visit. * History of hepatitis A or hepatitis B infection. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. * Acute disease at the time of. * Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the challenge dose or planned administration before the final blood sampling point (one month after the challenge dose). * Pregnant or lactating female.

Outcomes

Primary Outcomes

Anti-HAV Antibody Concentrations

Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations \>= 15 mIU/mL.

Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084

Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values

Anti-HBs antibody cut-off values assessed were \>= 6.2 mIU/mL and \>= 10 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA).

Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084

Anti-HBs Antibody Concentrations

Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations \>= 6.2 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA.

Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.

Anti-HBs Anamnestic Response.

Anamnestic response was defined as: Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points. At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points.

Time frame: One month after the challenge dose.

Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value.

Anti-HAV antibody cut-off value assessed was \>= 15 milli-International Units per milliliter (mIU/mL).

Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.