Hepatitis B Vaccine
Conditions
Keywords
Hepatitis B surface antigen antibody, adult subjects, Hepatitis B, HBV
Brief summary
The purpose of this study is to assess the long-term protection against HBV infection in adult subjects, aged 18-40 years vaccinated with three or four doses of Engerix-B 20 to 30 years ago
Interventions
BIOLOGICALEngerix-B
Intramuscular administration of single challenge dose of Engerix-B vaccine in the deltoid region of the non-dominant arm.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 60 Years
Healthy volunteers
Yes
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 40 and 60 years of age (from and including the 40th birthday up to, but excluding, the 61st birthday) at the time of the vaccination. * Written informed consent obtained from the subject. * Documented evidence of previous vaccination with three or four consecutive doses of Engerix-B administered in adulthood (i.e. at least 18 years of age) with * the last dose received 4 to 12 months after the previous one, * no subsequent booster dose ever received later, and * the last dose received 20 to 30 years before enrolment. * Female subjects of non-childbearing potential may be enrolled in the study. * Non-childbearing potential is defined as pre-menarche, 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 vaccination, and * has a negative pregnancy test on the day of vaccination, and * has agreed to continue adequate contraception during the entire treatment period and for one month after vaccination.
Exclusion criteria
* Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the dose of study vaccine, or planned use during the study period. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed. * Administration of long-acting immune-modifying drugs at any time during the study period. * Previous hepatitis B booster vaccination since completion of the primary vaccination series with three or four doses of Engerix-B. * Planned administration of a vaccine not foreseen by the study protocol within 30 days preceding the dose of study vaccine, or planned administration during the study period, with the exception of seasonal influenza vaccine. * Any medical condition that in the judgment of the investigator places the subject at undue risk by participating in the study. * 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 vaccine/product. * History of hepatitis B disease or episode of jaundice with unknown etiology. * History of any reaction or hypersensitivity 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. * Major congenital defects or serious chronic illness (including insulin-dependent diabetes). * Acute disease and/or fever at the time of enrolment. * Fever is defined as temperature ≥37.5°C for oral, axillary or tympanic route, or 38.0°C on rectal route. * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. * Administration of immunoglobulins and/or any blood products during the period starting 3 months before the dose of study vaccine, or planned administration during the study period. * Drug and/ or alcohol abuse within the last 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose | 7 days after the challenge dose (Day 7) | Anamnestic response to the challenge dose was defined as: At least (i.e. greater than or equal to \[≥\]) 4-fold rise in one month post-vaccination anti-hepatitis B surface antigen (anti-HBs) antibody concentrations in previously seropositive subjects (Subjects with anti-HBs antibody concentration ≥ 6.2 milli International Unit/Milliliter (mIU/mL) at the pre-challenge dose time point); In previously seronegative subjects (Subjects with anti-HBs antibody concentration \< 6.2 mIU/mL at the pre-challenge dose time point), anti-HBs antibody concentrations ≥10 mIU/mL at one month post-challenge dose time-point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HBs Antibody Concentrations | At the pre-challenge dose time-point (Day 0), at 7 days post-challenge dose time-point (Day 7) and at 30 days post-challenge dose time-point (Day 30) | Anti-HBs antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. |
| Number of Subjects With Any Solicited Local Adverse Events (AEs) | During the 4-day (Days 0-3) follow-up period after the challenge dose | Assessed solicited local symptoms were injection site pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. |
| Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | At the pre-challenge dose time-point (Day 0), at 7 days post-challenge time-point (Day 7) and at 30 days post-challenge time-point (Day 30) | Percentage of subjects with anti-HBs antibody concentrations ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL. |
| Number of Subjects With Any Unsolicited AEs | During the 31-day (Days 0-30) follow-up period after the challenge dose | An 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. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. |
| Number of Subjects With Any Serious Adverse Events (SAEs) | During the entire study period (Day 0 to Day 30) | SAEs assessed included any untoward medical occurrences that resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or congenital anomaly/birth defect in the offspring of a study subject. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. |
| Number of Subjects With Any Solicited General AEs | During the 4-day (Days 0-3) follow-up period after the challenge dose | Assessed solicited general symptoms were fatigue, fever (defined as axillary temperature ≥ 37.5 degrees Celsius \[°C\]) , gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain) and headache. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. |
Countries
Belgium, Canada
Participant flow
Recruitment details
Subjects aged between and including 40 to 60 years were enrolled in this study, in compliance with the inclusion criteria, which required the documented evidence of previous vaccination with three or four consecutive doses of Engerix-B administered in adulthood (i.e. at least 18 years of age).
Pre-assignment details
106 subjects were enrolled in the study but 3 subjects were withdrawn before vaccine administration. Therefore, the number of subjects started is 103.
Participants by arm
| Arm | Count |
|---|---|
| HBV Group Subjects aged 40 to 60 years old who received 3 or 4 doses of HBV vaccine 20 to 30 years ago and were administered with a single challenge dose of HBV vaccine in this study at Day 0 (Visit 1). | 103 |
| Total | 103 |
Baseline characteristics
| Characteristic | HBV Group |
|---|---|
| Age, Continuous | 48.6 Years STANDARD_DEVIATION 5.9 |
| Race/Ethnicity, Customized White - Caucasian / European Heritage | 103 Participants |
| Sex: Female, Male Female | 87 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 103 |
| other Total, other adverse events | 75 / 103 |
| serious Total, serious adverse events | 0 / 103 |
Outcome results
Primary
Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose
Anamnestic response to the challenge dose was defined as: At least (i.e. greater than or equal to \[≥\]) 4-fold rise in one month post-vaccination anti-hepatitis B surface antigen (anti-HBs) antibody concentrations in previously seropositive subjects (Subjects with anti-HBs antibody concentration ≥ 6.2 milli International Unit/Milliliter (mIU/mL) at the pre-challenge dose time point); In previously seronegative subjects (Subjects with anti-HBs antibody concentration \< 6.2 mIU/mL at the pre-challenge dose time point), anti-HBs antibody concentrations ≥10 mIU/mL at one month post-challenge dose time-point.
Time frame: 7 days after the challenge dose (Day 7)
Population: Analysis was performed on the According-to-protocol (ATP) cohort for analysis of immunogenicity which included all evaluable subjects who had received the challenge dose of HRV vaccine and for whom data concerning immunogenicity outcome measures at pre-challenge (Day 0) and one month post-challenge (Day 30) were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HBV Group | Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose | < 6.2 mIU/mL | 66.7 Percentage of subjects |
| HBV Group | Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose | ≥ 6.2 mIU/mL | 85.3 Percentage of subjects |
Primary
Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose
Anamnestic response to the challenge dose was defined as: At least (i.e. ≥ 4-fold rise in one month post-vaccination anti-HBs antibody concentrations in previously seropositive subjects (Subjects with anti-HBs antibody concentration ≥ 6.2 mIU/mL at the pre-challenge dose time point); In previously seronegative subjects (Subjects with anti-HBs antibody concentration \< 6.2 mIU/mL at the pre-challenge dose time point), anti-HBs antibody concentrations ≥10 mIU/mL at one month post-challenge dose time-point.
Time frame: 30 days after the challenge dose (Day 30)
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity which included all evaluable subjects who had received the challenge dose of HRV vaccine and for whom data concerning immunogenicity outcome measures at pre-challenge (Day 0) and one month post-challenge (Day 30) were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HBV Group | Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose | < 6.2 mIU/mL | 100 Percentage of subjects |
| HBV Group | Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose | ≥ 6.2 mIU/mL | 100 Percentage of subjects |
Secondary
Anti-HBs Antibody Concentrations
Anti-HBs antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
Time frame: At the pre-challenge dose time-point (Day 0), at 7 days post-challenge dose time-point (Day 7) and at 30 days post-challenge dose time-point (Day 30)
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity which included all evaluable subjects who had received the challenge dose of HRV vaccine and for whom data concerning immunogenicity outcome measures at pre-challenge (Day 0) and one month post-challenge (Day 30) were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| HBV Group | Anti-HBs Antibody Concentrations | At Day 0 | 184.6 mIU/mL |
| HBV Group | Anti-HBs Antibody Concentrations | At Day 7 | 3840.0 mIU/mL |
| HBV Group | Anti-HBs Antibody Concentrations | At Day 30 | 48999.1 mIU/mL |
Secondary
Number of Subjects With Any Serious Adverse Events (SAEs)
SAEs assessed included any untoward medical occurrences that resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or congenital anomaly/birth defect in the offspring of a study subject. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.
Time frame: During the entire study period (Day 0 to Day 30)
Population: Analysis was performed on the TVC which included all subjects who received the challenge dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBV Group | Number of Subjects With Any Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Number of Subjects With Any Solicited General AEs
Assessed solicited general symptoms were fatigue, fever (defined as axillary temperature ≥ 37.5 degrees Celsius \[°C\]) , gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain) and headache. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.
Time frame: During the 4-day (Days 0-3) follow-up period after the challenge dose
Population: Analysis was performed on the TVC which included all subjects who received the challenge dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HBV Group | Number of Subjects With Any Solicited General AEs | Any Fatigue | 27 Participants |
| HBV Group | Number of Subjects With Any Solicited General AEs | Any Gastrointestinal symptoms | 10 Participants |
| HBV Group | Number of Subjects With Any Solicited General AEs | Any Headache | 20 Participants |
| HBV Group | Number of Subjects With Any Solicited General AEs | Any Fever | 0 Participants |
Secondary
Number of Subjects With Any Solicited Local Adverse Events (AEs)
Assessed solicited local symptoms were injection site pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.
Time frame: During the 4-day (Days 0-3) follow-up period after the challenge dose
Population: Analysis was performed on the Total Vaccinated cohort (TVC) which included all subjects who received the challenge dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HBV Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) | Any Pain | 40 Participants |
| HBV Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) | Any Redness (mm) | 4 Participants |
| HBV Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) | Any Swelling (mm) | 3 Participants |
Secondary
Number of Subjects With Any Unsolicited AEs
An 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. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.
Time frame: During the 31-day (Days 0-30) follow-up period after the challenge dose
Population: Analysis was performed on the TVC which included all subjects who received the challenge dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBV Group | Number of Subjects With Any Unsolicited AEs | 41 Participants |
Secondary
Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values
Percentage of subjects with anti-HBs antibody concentrations ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL.
Time frame: At the pre-challenge dose time-point (Day 0), at 7 days post-challenge time-point (Day 7) and at 30 days post-challenge time-point (Day 30)
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity which included all evaluable subjects who had received the challenge dose of HRV vaccine and for whom data concerning immunogenicity outcome measures at pre-challenge (Day 0) and one month post-challenge (Day 30) were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 6.2 mIU/mL [Day 0] | 94.1 Percentage of subjects |
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 10 mIU/mL [Day 0] | 90.1 Percentage of subjects |
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 100 mIU/mL [Day 0] | 61.4 Percentage of subjects |
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 6.2 mIU/mL [Day 7] | 98.0 Percentage of subjects |
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 10 mIU/mL [Day 7] | 97.0 Percentage of subjects |
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 100 mIU/mL [Day 7] | 92.1 Percentage of subjects |
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 6.2 mIU/mL [Day 30] | 100 Percentage of subjects |
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 10 mIU/mL [Day 30] | 100 Percentage of subjects |
| HBV Group | Percentage of Subjects With Anti-HBs Antibody Concentrations Equal to or Above Cut-off Values | ≥ 100 mIU/mL [Day 30] | 98.0 Percentage of subjects |