Hepatitis B
Conditions
Keywords
Persistence, challenge dose, Engerix-B, immune response
Brief summary
This study will evaluate the persistence of immunity to hepatitis B 10 to 11 years after vaccination with Infanrix hexa™ or Engerix™-B and also the ability to mount an immune response to the challenge dose of Engerix™-B.
Detailed description
Subjects who participated in the primary study 217744/031 (NCT01457495) will be invited at the age of 11-12 years to participate in this follow-up study.
Interventions
BIOLOGICALEngerix™-B
Intramuscular, single dose
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to 12 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that their parents/Legally acceptable representative) can and will comply with the requirements of the protocol should be enrolled in the study. * A male or female aged 11-12 years at the time of study entry (from and including the 11th birthday until and excluding the 13th birthday). * Written informed consent obtained from the parent or Legally Acceptable Representative of the subject. * Study procedures will be explained to subjects and depending on their understanding, optional informed assent will be sought at the discretion of the investigator. * Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/ Legally Acceptable Representative (s). * Healthy subjects as established by medical history and clinical examination before entering into the study. * Subjects who have received all three doses of Infanrix hexa or Engerix-B in the primary study 217744/031 (NCT01457495). * Female subjects of non-childbearing potential may be enrolled in the study. * 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
* 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. * Child in care. * Use of any investigational or non-registered product drug or vaccine) other than the study vaccine within 30 days preceding the challenge dose of HBV vaccine, or planned use during the study period. * Receipt of hepatitis B (containing) vaccine after vaccination in the primary study 217744/031 (NCT01457495). * History of hepatitis B disease. * 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 vaccine challenge dose. * Administration of immunoglobulins and/or any blood products within the three months preceding the challenge dose of HBV vaccine or planned administration during the study period. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose of HBV vaccine. * 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. * Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL) | One month after a challenge dose of Engerix-B vaccine | A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL | Before and one month after a challenge dose of Engerix-B vaccine | A seropositive subject was defined as a subject with anti-HBs antibody concentration ≥ the 6.2 mIU/mLcut-off. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off. |
| Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL | Before and one month after a challenge dose of Engerix-B vaccine | A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. |
| Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL | Before the challenge dose of Engerix-B vaccine | A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. |
| Number of Subjects With an Anamnestic Response to a Challenge Dose | Before and one month after a challenge dose of Engerix-B vaccine | The anamnestic response was defined as: at least (≥) a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in seronegative subjects at the pre-challenge dose time point. A seropositive/seronegative subject is a subject with anti-HBs antibody concentration ≥/lower than (\<) 6.2 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off. |
| Number of Subjects Reporting Solicited General Symptoms | During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine | Solicited general symptoms assessed were fatigue, gastrointestinal, headache and temperature (Temperature is defined as axillary temparature equal to or above 37.5 degrees Celsius (°C)). |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | During the 31-day (Days 0-30) follow-up period after a challenge dose of Engerix-B vaccine | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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 Reporting Serious Adverse Events (SAEs) | After the challenge dose of Engerix-B vaccine up to the study end | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. |
| Number of Subjects Reporting Solicited Local Symptoms | During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine | Solicited local symptoms assessed were pain, redness and swelling. |
Countries
Slovakia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infanrix-hexa/Engerix-B Group Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm. | 95 |
| Infanrix-IPV+Hib/Engerix-B Group Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (NCT01457495) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm. | 90 |
| Total | 185 |
Baseline characteristics
| Characteristic | Infanrix-hexa/Engerix-B Group | Infanrix-IPV+Hib/Engerix-B Group | Total |
|---|---|---|---|
| Age, Continuous | 11.3 Years STANDARD_DEVIATION 0.46 | 11.3 Years STANDARD_DEVIATION 0.47 | 11.3 Years STANDARD_DEVIATION 0.47 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 45 Participants | 35 Participants | 80 Participants |
| Sex: Female, Male Male | 50 Participants | 55 Participants | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 95 | 0 / 90 |
| other Total, other adverse events | 48 / 95 | 43 / 90 |
| serious Total, serious adverse events | 1 / 95 | 0 / 90 |
Outcome results
Primary
Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL)
A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.
Time frame: One month after a challenge dose of Engerix-B vaccine
Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL) | 88 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL) | 84 Participants |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
Time frame: After the challenge dose of Engerix-B vaccine up to the study end
Population: The Total Vaccinated cohort included all subjects who received the challenge dose of Engerix-B vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 1 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Number of Subjects Reporting Solicited General Symptoms
Solicited general symptoms assessed were fatigue, gastrointestinal, headache and temperature (Temperature is defined as axillary temparature equal to or above 37.5 degrees Celsius (°C)).
Time frame: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine
Population: The Total Vaccinated cohort included all subjects who received the challenge dose of Engerix-B vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Solicited General Symptoms | Fatigue | 23 Participants |
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Solicited General Symptoms | Gastrointestinal | 9 Participants |
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Solicited General Symptoms | Headache | 19 Participants |
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Solicited General Symptoms | Temperature ≥ 37.5°C | 1 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Solicited General Symptoms | Temperature ≥ 37.5°C | 3 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Solicited General Symptoms | Fatigue | 22 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Solicited General Symptoms | Headache | 14 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Solicited General Symptoms | Gastrointestinal | 9 Participants |
Secondary
Number of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed were pain, redness and swelling.
Time frame: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine
Population: The Total Vaccinated cohort included all subjects who received the challenge dose of Engerix-B vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 30 Participants |
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 25 Participants |
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 15 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 24 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 22 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 8 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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 (Days 0-30) follow-up period after a challenge dose of Engerix-B vaccine
Population: The Total Vaccinated cohort included all subjects who received the challenge dose of Engerix-B vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 5 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 7 Participants |
Secondary
Number of Subjects With an Anamnestic Response to a Challenge Dose
The anamnestic response was defined as: at least (≥) a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in seronegative subjects at the pre-challenge dose time point. A seropositive/seronegative subject is a subject with anti-HBs antibody concentration ≥/lower than (\<) 6.2 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off.
Time frame: Before and one month after a challenge dose of Engerix-B vaccine
Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects With an Anamnestic Response to a Challenge Dose | 91 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects With an Anamnestic Response to a Challenge Dose | 86 Participants |
Secondary
Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL
A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.
Time frame: Before the challenge dose of Engerix-B vaccine
Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL | 14 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL | 17 Participants |
Secondary
Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL
A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.
Time frame: Before and one month after a challenge dose of Engerix-B vaccine
Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL | ≥ 10 mIU/mL [pre-challenge dose] | 46 Participants |
| Infanrix-hexa/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL | ≥ 10 mIU/mL [post-challenge dose] | 91 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL | ≥ 10 mIU/mL [pre-challenge dose] | 52 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL | ≥ 10 mIU/mL [post-challenge dose] | 88 Participants |
Secondary
Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL
A seropositive subject was defined as a subject with anti-HBs antibody concentration ≥ the 6.2 mIU/mLcut-off. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off.
Time frame: Before and one month after a challenge dose of Engerix-B vaccine
Population: The According-To-Protocol (ATP) cohort for analysis of immunogenicity included all evaluable subjects (i.e. those meeting eligibility criteria, complied with the procedures, with no elimination criteria) who had received a challenge dose Engerix-B vaccine and for whom immunogenicity data were available at the post-Engerix-B challenge time-point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Infanrix-hexa/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL | ≥ 6.2 mIU/mL [pre-challenge dose] | 53 Participants |
| Infanrix-hexa/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL | ≥ 6.2 mIU/mL [post-challenge dose] | 92 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL | ≥ 6.2 mIU/mL [pre-challenge dose] | 57 Participants |
| Infanrix-IPV+Hib/Engerix-B Group | Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL | ≥ 6.2 mIU/mL [post-challenge dose] | 88 Participants |