Hepatitis B
Conditions
Keywords
Hepatitis B, Persistence, Challenge dose
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.
Interventions
BIOLOGICALEngerix™-B
One dose (10µg Hepatitis B surface antigen (HBsAg))
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to 22 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Immunological Response to Challenge Dose in Terms of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | 30 days post-challenge dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-HBs Antibody Concentrations Above the Cut-off Value | 30 days post-challenge dose | Anti-HBs antibody cut-off values assessed include 3.3, 10 and 100 mIU/mL. |
| Concentration of Anti-HBs Antibodies | 30 days post-challenge dose | Concentrations given as geometric mean concentration (GMC) and expressed in mIU/mL. |
| Number of Participants Reporting Unsolicited Adverse Events (AE) | During the 31-day follow-up period (Day 0-30) after the challenge dose | 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. |
| Number of Participants Reporting Solicited General Symptoms | During the 4-day follow-up period (Day 0-3) after the challenge dose | Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms, and headache. |
| Number of Participants Reporting Serious Adverse Events (SAE) | During the 31-day follow-up period (Day 0-30) after the challenge dose | 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. |
| Number of Participants Reporting Solicited Local Symptoms | During the 4-day follow-up period (Day 0-3) after the challenge dose | Solicited local symptoms assessed include pain, redness and swelling. |
Countries
Australia, Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Engerix 2 Doses + Challenge Dose 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. | 97 |
| Engerix 3 Doses + Challenge Dose 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. | 47 |
| Total | 144 |
Baseline characteristics
| Characteristic | Engerix 2 Doses + Challenge Dose | Engerix 3 Doses + Challenge Dose | Total |
|---|---|---|---|
| Age, Continuous | 19.5 years STANDARD_DEVIATION 1.22 | 19.3 years STANDARD_DEVIATION 1.46 | 19.4 years STANDARD_DEVIATION 1.3 |
| Sex: Female, Male Female | 50 Participants | 23 Participants | 73 Participants |
| Sex: Female, Male Male | 47 Participants | 24 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 22 |
| other Total, other adverse events | 39 / 55 | 14 / 22 |
| serious Total, serious adverse events | 0 / 55 | 0 / 22 |
Outcome results
Primary
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.
Time frame: 30 days post-challenge dose
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity. Data from the Australian center were not included following data quality issues detected at the investigator site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix 2 Doses + Challenge Dose | Number of Participants With Immunological Response to Challenge Dose in Terms of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | 53 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants With Immunological Response to Challenge Dose in Terms of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | 21 participants |
Secondary
Concentration of Anti-HBs Antibodies
Concentrations given as geometric mean concentration (GMC) and expressed in mIU/mL.
Time frame: 30 days post-challenge dose
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity. Data from the Australian center were not included following data quality issues detected at the investigator site.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Engerix 2 Doses + Challenge Dose | Concentration of Anti-HBs Antibodies | 6214.1 mIU/mL |
| Engerix 3 Doses + Challenge Dose | Concentration of Anti-HBs Antibodies | 16564.3 mIU/mL |
Secondary
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.
Time frame: During the 31-day follow-up period (Day 0-30) after the challenge dose
Population: Analysis was performed on the Total Vaccinated Cohort. This table describes SAEs reported by all subjects except for those enrolled in the Australian center.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Serious Adverse Events (SAE) | 0 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Serious Adverse Events (SAE) | 0 participants |
Secondary
Number of Participants Reporting Solicited General Symptoms
Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms, and headache.
Time frame: During the 4-day follow-up period (Day 0-3) after the challenge dose
Population: Analysis was performed on the Total Vaccinated Cohort. Data from the Australian center were not included following data quality issues detected at the investigator site.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Solicited General Symptoms | Gastrointestinal disorder | 7 participants |
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Solicited General Symptoms | Fever ≥ 37.5 degree Celsius | 1 participants |
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Solicited General Symptoms | Headache | 14 participants |
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Solicited General Symptoms | Fatigue | 19 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Solicited General Symptoms | Headache | 4 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Solicited General Symptoms | Fever ≥ 37.5 degree Celsius | 0 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Solicited General Symptoms | Gastrointestinal disorder | 4 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Solicited General Symptoms | Fatigue | 7 participants |
Secondary
Number of Participants Reporting Solicited Local Symptoms
Solicited local symptoms assessed include pain, redness and swelling.
Time frame: During the 4-day follow-up period (Day 0-3) after the challenge dose
Population: Analysis was performed on the Total Vaccinated Cohort. Data from the Australian center were not included following data quality issues detected at the investigator site.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Solicited Local Symptoms | Pain | 22 participants |
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Solicited Local Symptoms | Redness | 11 participants |
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Solicited Local Symptoms | Swelling | 9 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Solicited Local Symptoms | Pain | 4 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Solicited Local Symptoms | Redness | 1 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Solicited Local Symptoms | Swelling | 0 participants |
Secondary
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.
Time frame: During the 31-day follow-up period (Day 0-30) after the challenge dose
Population: Analysis was performed on the Total Vaccinated Cohort. Data from the Australian center were not included following data quality issues detected at the investigator site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix 2 Doses + Challenge Dose | Number of Participants Reporting Unsolicited Adverse Events (AE) | 19 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants Reporting Unsolicited Adverse Events (AE) | 5 participants |
Secondary
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.
Time frame: 30 days post-challenge dose
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity. Data from the Australian center were not included following data quality issues detected at the investigator site.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Engerix 2 Doses + Challenge Dose | Number of Participants With Anti-HBs Antibody Concentrations Above the Cut-off Value | ≥ 3.3 mIU/mL | 53 participants |
| Engerix 2 Doses + Challenge Dose | Number of Participants With Anti-HBs Antibody Concentrations Above the Cut-off Value | ≥ 10 mIU/mL | 53 participants |
| Engerix 2 Doses + Challenge Dose | Number of Participants With Anti-HBs Antibody Concentrations Above the Cut-off Value | ≥ 100 mIU/mL | 50 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants With Anti-HBs Antibody Concentrations Above the Cut-off Value | ≥ 3.3 mIU/mL | 21 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants With Anti-HBs Antibody Concentrations Above the Cut-off Value | ≥ 10 mIU/mL | 21 participants |
| Engerix 3 Doses + Challenge Dose | Number of Participants With Anti-HBs Antibody Concentrations Above the Cut-off Value | ≥ 100 mIU/mL | 20 participants |