Hepatitis B
Conditions
Keywords
Hepatitis, vaccine
Brief summary
In this study, subjects who received primary neonatal vaccination with hepatitis B vaccine at 0, 1, 2, 12 months, 20 years ago in the 103860/272 primary study will be evaluated for immunological memory to hepatitis B vaccine via assessment of the response to a vaccine challenge dose.
Interventions
BIOLOGICALEngerix™-B
A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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 adult who received the complete neonatal primary vaccination course of hepatitis B vaccine (Engerix™-B), in the 103860/272 primary study approximately 20 years earlier. * Documented level of anti-HBs antibody concentrations \< 100 milli-international units per milliliter (mIU/ml) at the previous long-term time-point for which serological results are available for that subject. * Written informed consent obtained from 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 completion of the hepatitis B challenge dose.
Exclusion criteria
* 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. * Chronic administration (defined as more than 14 days) of immunosuppressants or 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 a booster dose of hepatitis B vaccine outside the context of this study between the long-term time-point at the documented level of anti-HBs antibody concentrations and the current challenge dose study 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, including human immunodeficiency virus (HIV) infection. * Acute disease at the time of enrolment. * Acute or chronic, clinically significant pulmonary, cardiovascular, 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. * Pregnant or lactating female. * Female planning to become pregnant or planning to discontinue contraceptive precautions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With an Immune Response to a Challenge Dose of Hepatitis B Vaccine | One month after the hepatitis B vaccine challenge dose | Immune response to a challenge dose of hepatitis B vaccine is defined as * at least a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive (≥ 3.3 mIU/mL) at the previous available long-term time point, or * a post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in subjects seronegative (\<3.3 mIU/mL) at the previous available long-term time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-HBs Antibody Concentrations Above Pre-defined Cut-off Values | One month after the hepatitis B vaccine challenge dose | Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 3.3, 10 and 100 mIU/mL. |
| Concentration of Anti-HBs Antibodies | One month after the hepatitis B vaccine challenge dose | Concentrations are given as Geometric Mean Concentrations (GMCs), calculated on subjects seropositive (subjects with anti-HBs antibody concentrations ≥ 3.3 mIU/mL) post-challenge dose. |
| Number of Subjects Reporting Unsolicited Adverse Events | During the 31-day follow-up period after the challenge dose of hepatitis B vaccine | An adverse event 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. |
| Number of Subjects Reporting Serious Adverse Events | During the 31-day follow-up period after the challenge dose of hepatitis B vaccine | A serious adverse event 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. |
Countries
Thailand
Participant flow
Recruitment details
Subjects who received primary neonatal Engerix™-B vaccination 20 years ago in the 103860/272 primary study and who had anti-hepatitis B surface antigen (HBs) antibody concentrations \< 100 milli-international units per milliliter (mIU/ml) at the previous available long-term time-point (NCT00240539), were invited to participate in the current study.
Participants by arm
| Arm | Count |
|---|---|
| Engerix Group Subjects received a challenge dose of hepatitis B vaccine (Engerix™-B). | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Engerix Group |
|---|---|
| Age, Continuous | 19.9 years STANDARD_DEVIATION 0.35 |
| Gender Female | 19 Participants |
| Gender Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Number of Subjects With an Immune Response to a Challenge Dose of Hepatitis B Vaccine
Immune response to a challenge dose of hepatitis B vaccine is defined as * at least a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive (≥ 3.3 mIU/mL) at the previous available long-term time point, or * a post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in subjects seronegative (\<3.3 mIU/mL) at the previous available long-term time point.
Time frame: One month after the hepatitis B vaccine challenge dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix Group | Number of Subjects With an Immune Response to a Challenge Dose of Hepatitis B Vaccine | 28 subjects |
Secondary
Concentration of Anti-HBs Antibodies
Concentrations are given as Geometric Mean Concentrations (GMCs), calculated on subjects seropositive (subjects with anti-HBs antibody concentrations ≥ 3.3 mIU/mL) post-challenge dose.
Time frame: One month after the hepatitis B vaccine challenge dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Engerix Group | Concentration of Anti-HBs Antibodies | 1082.4 mIU/mL |
Secondary
Number of Subjects Reporting Serious Adverse Events
A serious adverse event 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.
Time frame: During the 31-day follow-up period after the challenge dose of hepatitis B vaccine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix Group | Number of Subjects Reporting Serious Adverse Events | 0 subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events
An adverse event 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.
Time frame: During the 31-day follow-up period after the challenge dose of hepatitis B vaccine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix Group | Number of Subjects Reporting Unsolicited Adverse Events | 0 subjects |
Secondary
Number of Subjects With Anti-HBs Antibody Concentrations Above Pre-defined Cut-off Values
Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 3.3, 10 and 100 mIU/mL.
Time frame: One month after the hepatitis B vaccine challenge dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Engerix Group | Number of Subjects With Anti-HBs Antibody Concentrations Above Pre-defined Cut-off Values | ≥3.3 mIU/mL | 29 subjects |
| Engerix Group | Number of Subjects With Anti-HBs Antibody Concentrations Above Pre-defined Cut-off Values | ≥10 mIU/mL | 28 subjects |
| Engerix Group | Number of Subjects With Anti-HBs Antibody Concentrations Above Pre-defined Cut-off Values | ≥100 mIU/mL | 27 subjects |