Hepatitis B
Conditions
Keywords
Infanrix™ hexa, Hepatitis B antibodies, Immunogenicity, Hepatitis B, Adolescents, Infancy, Engerix™-B Kinder, Safety
Brief summary
The purpose of this study is to assess the long-term persistence of immunity to hepatitis B in adolescents aged 12-13 years who were vaccinated with four doses of Infanrix™-Hexa in infancy and to assess the anamnestic response, immunogenicity, safety and reactogenicity of a single challenge dose of the hepatitis B vaccine Engerix™-B Kinder.
Interventions
BIOLOGICALEngerix™-B Kinder
Single dose administered intramuscularly in deltoid region of non-dominant arm.
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' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit). * A male or female between the ages of 12 to 13 (from and including the 12th birthday, up to but excluding the 14th birthday) at the time of enrolment. * Subjects with documented evidence of previous vaccination with four consecutive doses of Infanrix hexa as part of routine vaccination in Germany: three doses of primary vaccination received by 9 months of age and one booster dose received between 11 and 18 months of age. * Written informed consent obtained from the parents/LAR(s) of the subject. * In addition to the informed consent that will be signed by the parents/LAR(s), written informed assent of the subject will be sought. * 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. * 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 series.
Exclusion criteria
* Child in care. * Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period. * Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). * Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccination. Inhaled and topical steroids are allowed. * Administration of any chronic drug therapy to be continued during the study period. * Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before and ending 30 days after the HBV challenge dose, with the exception of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (dTpa) vaccine, which can be given as part of routine vaccination practice. * 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 (pharmaceutical product or device). * Evidence of previous hepatitis B booster vaccination since administration of the fourth dose of Infanrix hexa booster in the second year of life. * History of or intercurrent hepatitis B disease. * Hepatitis B vaccination at birth. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * Family history of congenital or hereditary immunodeficiency. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. * Major congenital defects or serious chronic illness including thrombocytopenia and bleeding disorders. * History of any neurological disorders or seizures. * 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. The preferred route for recording temperature in this study will be axillary. * Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. * 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 3 months preceding the dose of study vaccine 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 |
|---|---|---|
| Anti-HBs Immune Response | One month after the single challenge dose of Engerix-B Kinder vaccine (Month 1) | Anti-HBs immune response was defined as the number of subjects with Anti-HBs antibody concentrations ≥ 100 mIU/ml. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml, ≥ 10 mIU/ml, 10 to < 100 mIU/ml and ≥ 100 mIU/ml. | Before the single challenge dose of Engerix-B Kinder vaccine. | A seropositive subject was defined as a subject with anti-HBs antibody concentrations ≥ 6.2 milli-international units per milliliter (mIU/ml). A seroprotected subjects was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/ml. |
| Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml and ≥ 10 mIU/ml. | 1 month after the single challenge dose of Engerix-B Kinder vaccine. | A seropositive subject was defined as a subject with anti-HBs antibody concentrations ≥ 6.2 mIU/ml. A seroprotected subjects was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/ml. |
| Number of Subjects With an Anamnestic Response to the Single Challenge Dose of Engerix-B Kinder Vaccine. | One month after the single challenge dose of Engerix-B Kinder vaccine. | The amnestic response to the challenge dose was defined as: for initially seronegative subjects, antibody concentration ≥ 10mIU/mL; for initially seropositive subjects, antibody concentration at least four times the pre-challenge antibody concentration. |
| Anti-HBs Antibody Concentrations at 12-13 Years of Age, After Previous Vaccination With Infanrix Hexa. | Before (PRE) and 1 month after (POST) the single challenge dose of Engerix-B Kinder vaccine. | Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of 6.2 mIU/ml. |
| Number of Subjects With Any Solicited General Symptoms. | During the 4-day (Day 0-3) follow-up period after the single challenge dose of Engerix-B Kinder vaccine. | Assessed solicited general symptoms were fatigue, gastrointestinal, headache and temperature \[defined as axillary temperature equal to oe above 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade. |
| Number of Subjects With Any Unsolicited Adverse Events (AEs). | During the 31-day (Day 0-30) follow-up period after the single challenge dose of Engerix-B Kinder vaccine. | An unsolicited AE covers 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 and 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. |
| Number of Subjects With Serious Adverse Events (SAEs). | From Month 0 to Month 1 | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. |
| Number of Subjects With Any Solicited Local Symptoms. | During the 4-day (Day 0-3) follow-up period after the single challenge dose of Engerix-B Kinder vaccine. | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. |
Countries
Germany
Participant flow
Pre-assignment details
301 subjects were enrolled in the study but one subject was withdrawn before any study procedure.
Participants by arm
| Arm | Count |
|---|---|
| Engerix-B Kinder Group Subjects who were previously primed and boosted with four doses of Infanrix hexa in the first two years of life, received a single dose of Engerix-B Kinder vaccine. The vaccine was administered intramuscularly into the deltoid of the non-dominant arm. | 300 |
| Total | 300 |
Baseline characteristics
| Characteristic | Engerix-B Kinder Group |
|---|---|
| Age, Continuous | 12.3 Years STANDARD_DEVIATION 0.5 |
| Sex: Female, Male Female | 150 Participants |
| Sex: Female, Male Male | 150 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 200 / 300 |
| serious Total, serious adverse events | 2 / 300 |
Outcome results
Primary
Anti-HBs Immune Response
Anti-HBs immune response was defined as the number of subjects with Anti-HBs antibody concentrations ≥ 100 mIU/ml.
Time frame: One month after the single challenge dose of Engerix-B Kinder vaccine (Month 1)
Population: The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects, who complied with the protocol, for whom immunogenicity data were available and for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination time points.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix-B Kinder Group | Anti-HBs Immune Response | 272 Subject |
Secondary
Anti-HBs Antibody Concentrations at 12-13 Years of Age, After Previous Vaccination With Infanrix Hexa.
Concentrations were expressed as geometric mean concentrations (GMCs) for the seropositivity cut-off of 6.2 mIU/ml.
Time frame: Before (PRE) and 1 month after (POST) the single challenge dose of Engerix-B Kinder vaccine.
Population: The analysis was performed on the According-To-Protocol cohort for persistence, which included all evaluable subjects, aged 12-13 years at the time of enrolment, who did not received any additional dose of hepatitis B vaccine other than four doses of Infanrix hexa during first two years of life, for whom the serological results were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Engerix-B Kinder Group | Anti-HBs Antibody Concentrations at 12-13 Years of Age, After Previous Vaccination With Infanrix Hexa. | Anti-HBs, PRE | 22.7 mIU/mL |
| Engerix-B Kinder Group | Anti-HBs Antibody Concentrations at 12-13 Years of Age, After Previous Vaccination With Infanrix Hexa. | Anti-HBs, POST | 3502.6 mIU/mL |
Secondary
Number of Subjects With an Anamnestic Response to the Single Challenge Dose of Engerix-B Kinder Vaccine.
The amnestic response to the challenge dose was defined as: for initially seronegative subjects, antibody concentration ≥ 10mIU/mL; for initially seropositive subjects, antibody concentration at least four times the pre-challenge antibody concentration.
Time frame: One month after the single challenge dose of Engerix-B Kinder vaccine.
Population: The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects, who complied with the protocol, for whom immunogenicity data were available and for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination time points.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix-B Kinder Group | Number of Subjects With an Anamnestic Response to the Single Challenge Dose of Engerix-B Kinder Vaccine. | 277 Subject |
Secondary
Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml, ≥ 10 mIU/ml, 10 to < 100 mIU/ml and ≥ 100 mIU/ml.
A seropositive subject was defined as a subject with anti-HBs antibody concentrations ≥ 6.2 milli-international units per milliliter (mIU/ml). A seroprotected subjects was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/ml.
Time frame: Before the single challenge dose of Engerix-B Kinder vaccine.
Population: The analysis was performed on the According-To-Protocol cohort for persistence, which included all evaluable subjects, aged 12-13 years at the time of enrolment, who did not received any additional dose of hepatitis B vaccine other than four doses of Infanrix hexa during first two years of life, for whom the serological results were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Engerix-B Kinder Group | Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml, ≥ 10 mIU/ml, 10 to < 100 mIU/ml and ≥ 100 mIU/ml. | Anti-HBs ≥ 6.2 mIU/ml | 205 Subject |
| Engerix-B Kinder Group | Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml, ≥ 10 mIU/ml, 10 to < 100 mIU/ml and ≥ 100 mIU/ml. | Anti-HBs ≥ 10 mIU/ml | 178 Subject |
| Engerix-B Kinder Group | Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml, ≥ 10 mIU/ml, 10 to < 100 mIU/ml and ≥ 100 mIU/ml. | Anti-HBs 10 to < 100 mIU/ml | 116 Subject |
| Engerix-B Kinder Group | Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml, ≥ 10 mIU/ml, 10 to < 100 mIU/ml and ≥ 100 mIU/ml. | Anti-HBs ≥ 100 mIU/ml | 62 Subject |
Secondary
Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml and ≥ 10 mIU/ml.
A seropositive subject was defined as a subject with anti-HBs antibody concentrations ≥ 6.2 mIU/ml. A seroprotected subjects was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/ml.
Time frame: 1 month after the single challenge dose of Engerix-B Kinder vaccine.
Population: The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects, who complied with the protocol, for whom immunogenicity data were available and for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Engerix-B Kinder Group | Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml and ≥ 10 mIU/ml. | Anti-HBs ≥ 6.2 mIU/ml | 283 Subject |
| Engerix-B Kinder Group | Number of Subjects With Anti-HBs Antibody Concentrations ≥ 6.2 mIU/ml and ≥ 10 mIU/ml. | Anti-HBs ≥ 10 mIU/ml | 282 Subject |
Secondary
Number of Subjects With Any Solicited General Symptoms.
Assessed solicited general symptoms were fatigue, gastrointestinal, headache and temperature \[defined as axillary temperature equal to oe above 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade.
Time frame: During the 4-day (Day 0-3) follow-up period after the single challenge dose of Engerix-B Kinder vaccine.
Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with the vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Engerix-B Kinder Group | Number of Subjects With Any Solicited General Symptoms. | Fatigue | 73 Subject |
| Engerix-B Kinder Group | Number of Subjects With Any Solicited General Symptoms. | Gastrointestinal | 34 Subject |
| Engerix-B Kinder Group | Number of Subjects With Any Solicited General Symptoms. | Headache | 71 Subject |
| Engerix-B Kinder Group | Number of Subjects With Any Solicited General Symptoms. | Temperature/(Axillary) | 7 Subject |
Secondary
Number of Subjects With Any Solicited Local Symptoms.
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
Time frame: During the 4-day (Day 0-3) follow-up period after the single challenge dose of Engerix-B Kinder vaccine.
Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with the vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Engerix-B Kinder Group | Number of Subjects With Any Solicited Local Symptoms. | Swelling | 29 Subject |
| Engerix-B Kinder Group | Number of Subjects With Any Solicited Local Symptoms. | Pain | 132 Subject |
| Engerix-B Kinder Group | Number of Subjects With Any Solicited Local Symptoms. | Redness | 70 Subject |
Secondary
Number of Subjects With Any Unsolicited Adverse Events (AEs).
An unsolicited AE covers 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 and 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time frame: During the 31-day (Day 0-30) follow-up period after the single challenge dose of Engerix-B Kinder vaccine.
Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with the vaccine administration documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix-B Kinder Group | Number of Subjects With Any Unsolicited Adverse Events (AEs). | 44 Subject |
Secondary
Number of Subjects With Serious Adverse Events (SAEs).
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time frame: From Month 0 to Month 1
Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with the vaccine administration documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Engerix-B Kinder Group | Number of Subjects With Serious Adverse Events (SAEs). | 2 Subject |