Hepatitis B
Conditions
Keywords
Healthy, Hepatitis B, Adolescents, Engerix™-B Kinder
Brief summary
The purpose of this study is to assess the long-term persistence of immunity to hepatitis B in adolescents aged 15-16 years who were vaccinated with Engerix™-B Kinder in infancy. The study will also assess the immune response to a challenge dose of Engerix™-B Kinder in these subjects.
Detailed description
This MDD has been updated following the Protocol Amendment 1, dated 20 June 2013. The Protocol was amended because GSK replaced its in-house Enzyme-Linked ImmunoSorbent Assay (ELISA) that was used to measure anti-HBs (antibodies to Hepatitis B surface antigen) antibody concentrations with ChemiLuminescence ImmunoAssay (CLIA). Additionally, the threshold level of prednisone was modified to reflect the dosage normally prescribed to adolescents.
Interventions
BIOLOGICALEngerix™-B Kinder
Single dose administered intramuscularly in the deltoid region of non-dominant arm at Day 0.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 16 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject's parent(s)/guardians who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. * A male or female between, and including, 15 and 16 years of age at the time of the vaccination. * Written informed consent obtained from the parent(s)/LAR(s) of the subject. * 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. * Documented evidence of previous vaccination with three consecutive doses of Engerix™-B Kinder in Germany: with the first two doses received by 9 months of age and the third dose received by 18 months of age. * Female subjects of non-childbearing potential may be enrolled in the study. * Non-childbearing potential is defined as pre-menarche, current tubal ligation, 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 2 months after completion of the vaccination.
Exclusion criteria
* Child in care. * Use of any investigational or non-registered product other than the study vaccine within 30 days preceding 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. * Previous hepatitis B vaccination since administration of the third dose of Engerix™-B Kinder. * History of hepatitis B disease. * Administration of a vaccine not foreseen by the study protocol within the period starting 30 days before study vaccine dose, or planned administration during the study period. * 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 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. * Acute disease and/or fever at the time of enrollment. * Fever is defined as temperature ≥ 37.5°C for oral, axillary or tympanic route, or ≥ 38.0°C on rectal route. The preferred route for recording temperature in this study will be axillary. * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. * Administration of immunoglobulins and/or any blood products within the 3 months preceding the study vaccine 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 Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the 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 |
|---|---|---|
| Antibody Titers Against Hepatitis B Virus | Before (Day 0) and one month (Month 1) after the challenge dose | Antibody titers were summarized by geometric mean concentrations (GMCs) with their 95% CIs. |
| Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status. | Prior to vaccination with 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 post-vaccination anti-HBs antibody concentrations in subjects seropositive at the pre-vaccination time point Post-vaccination anti-HB antibody concentrations ≥10 mIU/mL in subjects seronegative at the pre-vaccination time point |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | During the 4-day (Days 0-3) follow-up period after the challenge dose | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. \>50 mm. |
| Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | Before (Day 0) and one month after the challenge dose (Month 1) | The cut-off values defined were ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL. |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs). | During the 31-day (Days 0-30) follow-up period after the challenge dose | 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 was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. |
| Number of Subjects Reporting Any Serious Adverse Events (SAEs). | During the entire study period (Day 0 to Month 1) | Serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination. |
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | During the 4-day (Days 0-3) follow-up period after the challenge dose | Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever \[axillary temperature above 37.5 degrees Celsius (°C)\]. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C |
Countries
Germany
Participant flow
Pre-assignment details
One subject from the total number of 303 subjects enrolled did not qualify to start the study due to a protocol violation.
Participants by arm
| Arm | Count |
|---|---|
| HBV Group Subjects received a single dose of Engerix™-B Kinder vaccine (HBV). The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | 302 |
| Total | 302 |
Baseline characteristics
| Characteristic | HBV Group |
|---|---|
| Age, Continuous | 15.3 Years STANDARD_DEVIATION 0.5 |
| Sex: Female, Male Female | 139 Participants |
| Sex: Female, Male Male | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 169 / 302 |
| serious Total, serious adverse events | 2 / 302 |
Outcome results
Primary
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the 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 HBV and for whom data concerning immunogenicity outcome measures were available at the time point after the HBV challenge dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBV Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | 265 Participants |
Secondary
Antibody Titers Against Hepatitis B Virus
Antibody titers were summarized by geometric mean concentrations (GMCs) with their 95% CIs.
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 HBV and for whom data concerning immunogenicity outcome measures were available at the time point after the HBV challenge dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| HBV Group | Antibody Titers Against Hepatitis B Virus | Day 0 | 26.5 mIU/mL |
| HBV Group | Antibody Titers Against Hepatitis B Virus | Month 1 | 4134.9 mIU/mL |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. \>50 mm.
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 which included all subjects who received the challenge dose of HBV vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HBV Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Pain | 81 Participants |
| HBV Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Pain | 1 Participants |
| HBV Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Redness | 48 Participants |
| HBV Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Redness | 0 Participants |
| HBV Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Swelling | 16 Participants |
| HBV Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Swelling | 0 Participants |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever \[axillary temperature above 37.5 degrees Celsius (°C)\]. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C
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 which included all subjects who received the challenge dose of HBV vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue | 84 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue | 8 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue | 47 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal symptoms | 41 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal symptoms | 1 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal symptoms | 21 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Headache | 67 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache | 4 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Headache | 41 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Fever (≥ 37.5°C) | 7 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fever (> 39.0°C) | 0 Participants |
| HBV Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Fever | 4 Participants |
Secondary
Number of Subjects Reporting Any Serious Adverse Events (SAEs).
Serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination.
Time frame: During the entire study period (Day 0 to Month 1)
Population: Analysis was performed on the Total Vaccinated cohort which included all subjects who received the challenge dose of HBV vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBV Group | Number of Subjects Reporting Any Serious Adverse Events (SAEs). | 2 Participants |
Secondary
Number of Subjects Reporting 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. Any was defined as occurrence of any unsolicited 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 Total Vaccinated cohort which included all subjects who received the challenge dose of HBV vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBV Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs). | 46 Participants |
Secondary
Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status.
Anamnestic response to the challenge dose was defined as: At least (i.e. greater than or equal to ) 4-fold rise in post-vaccination anti-HBs antibody concentrations in subjects seropositive at the pre-vaccination time point Post-vaccination anti-HB antibody concentrations ≥10 mIU/mL in subjects seronegative at the pre-vaccination time point
Time frame: Prior to vaccination with 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 HBV and for whom data concerning immunogenicity outcome measures were available at the time point after the HBV challenge dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HBV Group | Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status. | Day 0 < 6.2 mIU/mL | 78 Participants |
| HBV Group | Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status. | Day 0 ≥ 6.2 mIU/mL | 204 Participants |
| HBV Group | Number of Subjects With an Anamnestic Response to the Challenge Dose in Relation to Their Pre Vaccination Status. | Total | 282 Participants |
Secondary
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value.
The cut-off values defined were ≥ 6.2 mIU/mL, ≥ 10 mIU/mL and ≥ 100 mIU/mL.
Time frame: Before (Day 0) and 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 HBV and for whom data concerning immunogenicity outcome measures were available at the time point after the HBV challenge dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HBV Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | Day 0 (≥ 6.2 mI/mL) | 208 Participants |
| HBV Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | Month 1 (≥ 6.2 mI/mL) | 287 Participants |
| HBV Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | Day 0 (≥ 10 mIU/mL) | 191 Participants |
| HBV Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | Month 1 (≥ 10 mIU/mL) | 286 Participants |
| HBV Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | Day 0 (≥ 100 mIU/mL) | 68 Participants |
| HBV Group | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut Off Value. | Month 1 (≥ 100 mIU/mL) | 265 Participants |