Hepatitis B
Conditions
Keywords
persistence, HBV, Long-term, Engerix™-B Kinder, Hepatitis B, adolescent
Brief summary
This phase IV open study will evaluate the persistence of humoral antibodies against hepatitis B as well as the immune response to a challenge dose of hepatitis B vaccine in adolescents aged 12-13 years, who received three consecutive doses of GSK Biologicals' recombinant hepatitis B vaccine (Engerix™-B) in infancy.
Interventions
BIOLOGICALEngerix™-B Kinder
Intramuscular, one dose.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 13 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that their parent(s)/Legally Accepted representative (LAR(s)) can and will comply with the requirements of the protocol. * A male or female of 12 to 13 years of age at the time of enrolment. * With documented evidence of previous vaccination with three consecutive doses of Engerix-B in Germany: with the first two doses received by 9 months of age and the third dose received by 18 months of age. * Written informed consent obtained from the parent(s) or LAR(s) of the subject at the time of enrolment. * Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/LAR(s). * Healthy subjects as established by medical history and clinical examination before entering into the study. * Female subjects of non-childbearing potential may be enrolled in the study. * Females of childbearing potential at the time of study entry must have a negative pregnancy test prior to administration of the dose of vaccine and are required to be abstinent or to use adequate contraceptive precautions for one month prior to vaccination. Subjects are required to agree to continue such precautions for two months after vaccination.
Exclusion criteria
* 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. * Evidence of previous hepatitis B booster vaccination since administration of the third dose of Engerix-B vaccine. * History of hepatitis B disease. * Hepatitis B vaccination at birth. * Adolescents living in institutional care. * Planned administration /administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before HBV vaccine challenge and ending 30 days after. * Administration of immunoglobulins and/or any blood products within the three months preceding HBV vaccine challenge or planned administration during the study period. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the HBV vaccine challenge.. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the challenge dose of study vaccine, or planned use during the study period. * Pregnant or lactating female. * Female planning to become pregnant or planning to discontinue contraceptive precautions. * Known hypersensitivity to any component of the HBV vaccine or evidence of hypersensitivity after previous immunisation with a vaccine containing the hepatitis B component. * Acute disease and/or fever at the time of enrolment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Value | One month after the challenge dose (Month 1) | The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL). |
| Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations as Measured by ChemiLuminescence ImmunoAssay (CLIA) Equal to or Above Cut-off Value. | One month after the challenge dose (Month 1) | The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Solicited Local and General Symptoms | During the 4-day (Day 0-3) follow-up period following the challenge dose vaccination | Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, gastrointestinal symptoms, headache and fever. Fever was defined as axillary temperature greater than or equal to 37.5 degrees Celsius. |
| Number of Subjects With Unsolicited Adverse Events (AEs) | During the 31-day (Day 0-30) follow-up period following the challenge dose vaccination | Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. |
| Number of Subjects With Anti-HBs Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Values | Before (Day 0) and one month (Month 1) after the challenge dose | The cut-off values were defined as 3.3 mIU/mL, 10 mIU/mL and 100 mIU/mL. Note: the number of subjects with anti-HBs antibody concentrations equal to or above 100 mIU/mL on month post-challenge dose data are presented as a primary outcome measure. |
| Number of Subjects With Anamnestic Response to the Challenge Dose as Measured by ELISA. | One month after the challenge dose (Month 1) | Anamnestic response was defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge vaccine dose anti-HBs antibody concentrations in subjects seropositive (i.e. with anti-HBs antibody concentration equal to or greater than 3.3 mIU/mL) at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations equal to or greater than 10 mIU/mL in subjects seronegative (i.e. with anti-HBs antibody concentrations less than 3.3 mIU/mL) at the pre-challenge dose time point. |
| Number of Subjects With Anamnestic Response to the Challenge Dose as Measured by CLIA. | One month after the challenge dose (Month 1) | Anamnestic response was defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge vaccine dose anti-HBs antibody concentrations in subjects seropositive (i.e. with anti-HBs antibody concentration ≥ 6.2 mIU/mL) at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations equal to or greater than 10 mIU/mL in subjects seronegative (i.e. with anti-HBs antibody concentrations \< 6.2 mIU/mL) at the pre-challenge dose time point. |
| Number of Subjects With Serious Adverse Events (SAEs) | After the challenge dose of the vaccine (Day 0) up to the study end (Month 1) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
| Number of Subjects With Anti-HBs Antibody Concentrations as Measured by CLIA Equal to or Above Cut-off Values | Before (Day 0) and one month (Month 1) after the challenge dose | The cut-off values were defined as 6.2 mIU/mL, 10 mIU/mL and 100 mIU/mL. Note: the number of subjects with anti-HBs antibody concentrations equal to or above 100 mIU/mL on month post-challenge dose data are presented as a primary outcome measure. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Engerix-B Group Subjects who were vaccinated with 3 doses of Engerix-B in infancy and who received a single challenge dose of Engerix-B , intramuscularly in the deltoid region of the non-dominant arm, at 12-13 years of age (Day 0). | 306 |
| Total | 306 |
Baseline characteristics
| Characteristic | Engerix-B Group |
|---|---|
| Age, Continuous | 12.4 Years STANDARD_DEVIATION 0.49 |
| Sex: Female, Male Female | 152 Participants |
| Sex: Female, Male Male | 154 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 170 / 306 |
| serious Total, serious adverse events | 0 / 306 |
Outcome results
Primary
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations as Measured by ChemiLuminescence ImmunoAssay (CLIA) Equal to or Above Cut-off Value.
The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL).
Time frame: One month after the challenge dose (Month 1)
Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of Engerix-B and for whom data concerning immunogenicity outcome measures were available at the time point after the Engerix-B challenge dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engerix-B Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations as Measured by ChemiLuminescence ImmunoAssay (CLIA) Equal to or Above Cut-off Value. | 257 Participants |
Primary
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Value
The cut-off value was defined as 100 milli-international units per milliliter (mIU/mL).
Time frame: One month after the challenge dose (Month 1)
Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of Engerix-B and for whom data concerning immunogenicity outcome measures were available at the time point after the Engerix-B challenge dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engerix-B Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Value | 266 Participants |
Secondary
Number of Subjects With Anamnestic Response to the Challenge Dose as Measured by CLIA.
Anamnestic response was defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge vaccine dose anti-HBs antibody concentrations in subjects seropositive (i.e. with anti-HBs antibody concentration ≥ 6.2 mIU/mL) at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations equal to or greater than 10 mIU/mL in subjects seronegative (i.e. with anti-HBs antibody concentrations \< 6.2 mIU/mL) at the pre-challenge dose time point.
Time frame: One month after the challenge dose (Month 1)
Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of Engerix-B and for whom data concerning immunogenicity outcome measures were available at the time point after the Engerix-B challenge dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engerix-B Group | Number of Subjects With Anamnestic Response to the Challenge Dose as Measured by CLIA. | 267 Participants |
Secondary
Number of Subjects With Anamnestic Response to the Challenge Dose as Measured by ELISA.
Anamnestic response was defined as: - At least (i.e. greater than or equal to) a 4-fold rise in post-challenge vaccine dose anti-HBs antibody concentrations in subjects seropositive (i.e. with anti-HBs antibody concentration equal to or greater than 3.3 mIU/mL) at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations equal to or greater than 10 mIU/mL in subjects seronegative (i.e. with anti-HBs antibody concentrations less than 3.3 mIU/mL) at the pre-challenge dose time point.
Time frame: One month after the challenge dose (Month 1)
Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of Engerix-B and for whom data concerning immunogenicity outcome measures were available at the time point after the Engerix-B challenge dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engerix-B Group | Number of Subjects With Anamnestic Response to the Challenge Dose as Measured by ELISA. | 274 Participants |
Secondary
Number of Subjects With Anti-HBs Antibody Concentrations as Measured by CLIA Equal to or Above Cut-off Values
The cut-off values were defined as 6.2 mIU/mL, 10 mIU/mL and 100 mIU/mL. Note: the number of subjects with anti-HBs antibody concentrations equal to or above 100 mIU/mL on month post-challenge dose data are presented as a primary outcome measure.
Time frame: Before (Day 0) and one month (Month 1) after the challenge dose
Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of Engerix-B and for whom data concerning immunogenicity outcome measures were available at the time point after the Engerix-B challenge dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by CLIA Equal to or Above Cut-off Values | pre challenge dose 6.2 mIU/mL | 201 Participants |
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by CLIA Equal to or Above Cut-off Values | post challenge dose 6.2 mIU/mL | 271 Participants |
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by CLIA Equal to or Above Cut-off Values | pre challenge dose 10 mIU/mL | 181 Participants |
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by CLIA Equal to or Above Cut-off Values | post challenge dose 10 mIU/mL | 271 Participants |
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by CLIA Equal to or Above Cut-off Values | pre challenge dose 100 mIU/mL | 67 Participants |
Secondary
Number of Subjects With Anti-HBs Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Values
The cut-off values were defined as 3.3 mIU/mL, 10 mIU/mL and 100 mIU/mL. Note: the number of subjects with anti-HBs antibody concentrations equal to or above 100 mIU/mL on month post-challenge dose data are presented as a primary outcome measure.
Time frame: Before (Day 0) and one month (Month 1) after the challenge dose
Population: The analysis was performed on the according-to-protocol (ATP) cohort of immunogenicity on all evaluable subjects who had received a challenge dose of Engerix-B and for whom data concerning immunogenicity outcome measures were available at the time point after the Engerix-B challenge dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Values | pre challenge dose 3.3 mIU/mL | 259 Participants |
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Values | post challenge dose 3.3 mIU/mL | 283 Participants |
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Values | pre challenge dose 10 mIU/mL | 220 Participants |
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Values | post challenge dose 10 mIU/mL | 281 Participants |
| Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentrations as Measured by ELISA Equal to or Above Cut-off Values | pre challenge dose 100 mIU/mL | 70 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: After the challenge dose of the vaccine (Day 0) up to the study end (Month 1)
Population: The analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engerix-B Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Number of Subjects With Solicited Local and General Symptoms
Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, gastrointestinal symptoms, headache and fever. Fever was defined as axillary temperature greater than or equal to 37.5 degrees Celsius.
Time frame: During the 4-day (Day 0-3) follow-up period following the challenge dose vaccination
Population: The analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engerix-B Group | Number of Subjects With Solicited Local and General Symptoms | pain | 104 Participants |
| Engerix-B Group | Number of Subjects With Solicited Local and General Symptoms | redness | 56 Participants |
| Engerix-B Group | Number of Subjects With Solicited Local and General Symptoms | swelling | 26 Participants |
| Engerix-B Group | Number of Subjects With Solicited Local and General Symptoms | fatigue | 63 Participants |
| Engerix-B Group | Number of Subjects With Solicited Local and General Symptoms | gastrointestinal symptoms | 14 Participants |
| Engerix-B Group | Number of Subjects With Solicited Local and General Symptoms | headache | 56 Participants |
| Engerix-B Group | Number of Subjects With Solicited Local and General Symptoms | fever | 9 Participants |
Secondary
Number of Subjects With Unsolicited Adverse Events (AEs)
Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time frame: During the 31-day (Day 0-30) follow-up period following the challenge dose vaccination
Population: The analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engerix-B Group | Number of Subjects With Unsolicited Adverse Events (AEs) | 64 Participants |