Hepatitis A, Hepatitis B
Conditions
Keywords
Monovalent Hepatitis A, hepatitis B vaccine, Belgium and Czech Republic
Brief summary
This study will evaluate the immune response against Hepatitis-A (HAV) and Hepatitis B surface (HBs) antigen in healthy subjects aged 12 to 15 years (at the time of primary vaccination), who received vaccination course with GSK Biologicals' Twinrix Adult and Twinrix Junior vaccine, approximately 10 years ago in the primary study. The subjects will be invited for blood sampling at 11, 12, 13, 14 and 15 years after primary vaccination to evaluate the persistence of immune response. For subjects detected with decreased immunity, the presence of immune memory against hepatitis A & B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine 6 to 12 months after the Year 15 follow-up time-point. No new subjects will be recruited during this booster phase of the study.
Interventions
PROCEDUREBlood sampling
Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
BIOLOGICALAdditional challenge dose
If a subject became seronegative for anti-HAV antibodies (\< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 15 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study * Written informed consent obtained from the subject. All subjects must satisfy the following criteria at entry into the challenge dose phase: * A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study. * Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points. * Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * Written informed consent obtained from the subject. * Healthy subjects as established by medical history and clinical examination before entering into the challenge dose phase of this study. * If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.
Exclusion criteria
The following criteria should be checked at each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit. * Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit. * Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study. * History of hepatitis A or hepatitis B infection. * Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 months prior to blood sampling. The following criteria should be checked before the challenge dose phase. If any apply, the subject must not be included in the challenge dose phase: * Use of any investigational or non-registered product (drug or vaccine) within 30 days before the administration of the challenge dose or planned use during the study period outside the context of the study. * Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine between the primary vaccination course of the primary study and the challenge dose visit. * History of hepatitis A or hepatitis B infection. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. * Acute disease at the time of. * Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the challenge dose or planned administration before the final blood sampling point (one month after the challenge dose). * Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HAV Antibody Concentrations | At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084 | Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations \>= 15 mIU/mL. |
| Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084 | Anti-HBs antibody cut-off values assessed were \>= 6.2 mIU/mL and \>= 10 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA). |
| Anti-HBs Antibody Concentrations | At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084. | Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations \>= 6.2 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA. |
| Anti-HBs Anamnestic Response. | One month after the challenge dose. | Anamnestic response was defined as: Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points. At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points. |
| Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084. | Anti-HAV antibody cut-off value assessed was \>= 15 milli-International Units per milliliter (mIU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | Since the last long-term follow-up visit up to Year 11. | 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 Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value. | Before (PRE) the challenge dose | Anti-HAV antibody cut-off value assessed was \>= 15 milli-International Units per milliliter (mIU/mL). Note: Since none of the subjects were seronegative for anti-HAV antibody concentration at the pre-challenge time point, subjects received only the HBV vaccine as the challenge dose. |
| Anti-HAV Antibody Concentrations | Before (PRE) the challenge dose | Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations \>= 15 mIU/mL. |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. |
| Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | Before (PRE) and one month after (POST) the challenge dose | Anti-HBs antibody cut-off values assessed were \>= 6.2 mIU/mL and \>= 10 mIU/mL |
| Anti-HBs Antibody Concentrations | Before (PRE) and one month after (POST) the challenge dose | Antibody concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations \>= 6.2 mIU/mL. |
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose. | Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever (axillary temperature). Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature \> 39.5°C. Related = general symptoms which were assessed by the investigator as causally related to vaccination. |
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms. | During the 31-day (Day 0 to 30) follow-up period after the challenge dose. | 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. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. Grade 3 = AE that prevented normal activity. Related = AE assessed by the investigator as causally related to the study vaccination. |
| Number of Subjects With Serious Adverse Events (SAEs). | One month after the administration of the challenge dose (Month 0 to Month 1) | Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. |
Countries
Belgium, Czechia
Participant flow
Pre-assignment details
In this study, a total of 210 subjects were enrolled who participated at Year 11 (Y11) and Y12. There were a total of 8 additional subjects at Y13 and Y14 who came back from the primary study but did not participate in Y11 and Y12 as allowed by the protocol. One subject from the 210 subjects who participated in Y11 and Y12 did not return at Y15.
Participants by arm
| Arm | Count |
|---|---|
| Twinrix Adult Group Subjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study | 102 |
| Twinrix Junior Group Subjects received 3 doses of Twinrix™ Junior (= half dose Twinrix™ Adult) intramuscularly according to a 0, 1, 6 month schedule in the primary study | 113 |
| Total | 215 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Challenge Dose Epoch | Pregnancy | 1 | 0 |
Baseline characteristics
| Characteristic | Twinrix Junior Group | Total | Twinrix Adult Group |
|---|---|---|---|
| Age, Continuous | 26.4 Years STANDARD_DEVIATION 1.06 | 26.40 Years STANDARD_DEVIATION 1.06 | 27.40 Years STANDARD_DEVIATION 1.11 |
| Sex: Female, Male Female | 53 Participants | 103 Participants | 50 Participants |
| Sex: Female, Male Male | 4 Participants | 110 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 7 / 11 |
| serious Total, serious adverse events | 1 / 102 | 0 / 113 |
Outcome results
Primary
Anti-HAV Antibody Concentrations
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations \>= 15 mIU/mL.
Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084
Population: Analysis was performed on subjects from the Long Term According-to-Protocol (LT ATP) cohort for immunogenicity on anti-HAV seropositive subjects with available data at the specified time-points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Adult Group | Anti-HAV Antibody Concentrations | Year 12 (N= 75; 90) | 450.8 mIU/mL |
| Twinrix Adult Group | Anti-HAV Antibody Concentrations | Year 14 (N= 75; 91) | 388.0 mIU/mL |
| Twinrix Adult Group | Anti-HAV Antibody Concentrations | Year 13 (N= 77; 92) | 401.5 mIU/mL |
| Twinrix Adult Group | Anti-HAV Antibody Concentrations | Year 15 (N= 74; 88) | 387.5 mIU/mL |
| Twinrix Adult Group | Anti-HAV Antibody Concentrations | Year 11 (N= 78; 92) | 360.5 mIU/mL |
| Twinrix Junior Group | Anti-HAV Antibody Concentrations | Year 15 (N= 74; 88) | 299.4 mIU/mL |
| Twinrix Junior Group | Anti-HAV Antibody Concentrations | Year 11 (N= 78; 92) | 257.2 mIU/mL |
| Twinrix Junior Group | Anti-HAV Antibody Concentrations | Year 12 (N= 75; 90) | 335.6 mIU/mL |
| Twinrix Junior Group | Anti-HAV Antibody Concentrations | Year 13 (N= 77; 92) | 293.6 mIU/mL |
| Twinrix Junior Group | Anti-HAV Antibody Concentrations | Year 14 (N= 75; 91) | 291.4 mIU/mL |
Primary
Anti-HBs Anamnestic Response.
Anamnestic response was defined as: Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points. At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points.
Time frame: One month after the challenge dose.
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Adult Group | Anti-HBs Anamnestic Response. | 8 Subjects |
| Twinrix Junior Group | Anti-HBs Anamnestic Response. | 10 Subjects |
Primary
Anti-HBs Antibody Concentrations
Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations \>= 6.2 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA.
Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.
Population: Analysis was performes on subjects from the Long Term According-to-Protocol (LT ATP) cohort forimmunogenicity on anti-HBs seropositive subjects with available data at the specified time-points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Adult Group | Anti-HBs Antibody Concentrations | Year 12 (N = 75;90) | 93.3 mIU/mL |
| Twinrix Adult Group | Anti-HBs Antibody Concentrations | Year 14 (N= 75;91) | 81.8 mIU/mL |
| Twinrix Adult Group | Anti-HBs Antibody Concentrations | Year 13 (N = 77;92) | 92.4 mIU/mL |
| Twinrix Adult Group | Anti-HBs Antibody Concentrations | Year 15 (N= 74;88) | 87.2 mIU/mL |
| Twinrix Adult Group | Anti-HBs Antibody Concentrations | Year 11 (N = 78;91) | 88.0 mIU/mL |
| Twinrix Junior Group | Anti-HBs Antibody Concentrations | Year 15 (N= 74;88) | 69.6 mIU/mL |
| Twinrix Junior Group | Anti-HBs Antibody Concentrations | Year 11 (N = 78;91) | 75.2 mIU/mL |
| Twinrix Junior Group | Anti-HBs Antibody Concentrations | Year 12 (N = 75;90) | 77.0 mIU/mL |
| Twinrix Junior Group | Anti-HBs Antibody Concentrations | Year 13 (N = 77;92) | 70.1 mIU/mL |
| Twinrix Junior Group | Anti-HBs Antibody Concentrations | Year 14 (N= 75;91) | 70.2 mIU/mL |
Primary
Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value.
Anti-HAV antibody cut-off value assessed was \>= 15 milli-International Units per milliliter (mIU/mL).
Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.
Population: Analysis was performed on subjects from the Long Term According-to-Protocol (LT ATP) cohort for immunogenicity on subjects with available data at the specified time-points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 12 (N= 75; 90) | 75 subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 14 (N= 75; 91) | 75 subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 13 (N= 77; 92) | 76 subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 15 (N= 74; 88) | 74 subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 11 (N= 78; 92) | 78 subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 15 (N= 74; 88) | 88 subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 11 (N= 78; 92) | 92 subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 12 (N= 75; 90) | 90 subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 13 (N= 77; 92) | 92 subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. | Year 14 (N= 75; 91) | 91 subjects |
Primary
Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values
Anti-HBs antibody cut-off values assessed were \>= 6.2 mIU/mL and \>= 10 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA).
Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084
Population: Analysis was performed on subjects from the Long Term According-to-Protocol (LT ATP) cohort for immunogenicity on subjects with available data at the specified time-points
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 11 [6.2 mIU/mL] (N = 78;91) | 68 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 12 [6.2 mIU/mL] (N = 75;90) | 64 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 13 [6.2 mIU/mL] (N = 77;92) | 65 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 14 [6.2 mIU/mL] (N= 75;91) | 66 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 15 [6.2 mIU/mL] (N= 74;88) | 62 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 11 [10 mIU/mL] (N = 78;91) | 64 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 12 [10 mIU/mL] (N = 75;90) | 62 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 13 [10 mIU/mL] (N = 77;92) | 62 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 14 [10 mIU/mL] (N= 75;91) | 62 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 15 [10 mIU/mL] (N= 74;88) | 60 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 13 [10 mIU/mL] (N = 77;92) | 77 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 11 [6.2 mIU/mL] (N = 78;91) | 79 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 11 [10 mIU/mL] (N = 78;91) | 75 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 12 [6.2 mIU/mL] (N = 75;90) | 80 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 15 [10 mIU/mL] (N= 74;88) | 72 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 13 [6.2 mIU/mL] (N = 77;92) | 83 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 12 [10 mIU/mL] (N = 75;90) | 76 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 14 [6.2 mIU/mL] (N= 75;91) | 80 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 14 [10 mIU/mL] (N= 75;91) | 73 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values | Year 15 [6.2 mIU/mL] (N= 74;88) | 79 Subjects |
Secondary
Anti-HAV Antibody Concentrations
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations \>= 15 mIU/mL.
Time frame: Before (PRE) the challenge dose
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Twinrix Adult Group | Anti-HAV Antibody Concentrations | 270.9 mIU/mL |
| Twinrix Junior Group | Anti-HAV Antibody Concentrations | 201.3 mIU/mL |
Secondary
Anti-HBs Antibody Concentrations
Antibody concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations \>= 6.2 mIU/mL.
Time frame: Before (PRE) and one month after (POST) the challenge dose
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Adult Group | Anti-HBs Antibody Concentrations | PRE (N= 8;11) | 3.1 mIU/mL |
| Twinrix Adult Group | Anti-HBs Antibody Concentrations | POST (N= 8;11) | 3022.8 mIU/mL |
| Twinrix Junior Group | Anti-HBs Antibody Concentrations | PRE (N= 8;11) | 4.1 mIU/mL |
| Twinrix Junior Group | Anti-HBs Antibody Concentrations | POST (N= 8;11) | 1433.1 mIU/mL |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events.
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
Time frame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Adult Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Grade 3 Swelling | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Grade 3 Redness | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Any Pain | 5 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Any Redness | 1 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Grade 3 Pain | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Any Swelling | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Any Swelling | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Any Redness | 2 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Grade 3 Redness | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Grade 3 Swelling | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Any Pain | 4 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. | Grade 3 Pain | 0 Subjects |
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). Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature \> 39.5°C. Related = general symptoms which were assessed by the investigator as causally related to vaccination.
Time frame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose.
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue | 3 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue | 3 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal symptoms | 1 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal symptoms | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal symptoms | 1 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Headache | 1 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Headache | 1 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Headache | 2 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue | 3 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue | 3 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal symptoms | 1 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal symptoms | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Headache | 2 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal symptoms | 1 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache | 0 Subjects |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms.
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. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. Grade 3 = AE that prevented normal activity. Related = AE assessed by the investigator as causally related to the study vaccination.
Time frame: During the 31-day (Day 0 to 30) follow-up period after the challenge dose.
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms. | Any AE(s) | 4 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms. | Grade 3 AE(s) | 0 Subjects |
| Twinrix Adult Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms. | Related AE(s) | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms. | Any AE(s) | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms. | Grade 3 AE(s) | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms. | Related AE(s) | 0 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 15.
Population: Analysis was performed on Long Term (LT) Total Cohort which included all subjects who returned at the current follow-up study and who belonged to the Total cohort in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Adult Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 11.
Population: Analysis was performed on Long Term (LT) Total Cohort which included all subjects who returned at the current follow-up study and who belonged to the Total cohort in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Adult Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 subjects |
| Twinrix Junior Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 12.
Population: Analysis was performed on Long Term (LT) Total Cohort which included all subjects who returned at the current follow-up study and who belonged to the Total cohort in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Adult Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 subjects |
| Twinrix Junior Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 13.
Population: Analysis was performed on Long Term (LT) Total Cohort which included all subjects who returned at the current follow-up study and who belonged to the Total cohort in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Adult Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 subjects |
| Twinrix Junior Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 14.
Population: Analysis was performed on Long Term (LT) Total Cohort which included all subjects who returned at the current follow-up study and who belonged to the Total cohort in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Adult Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 Subjects |
| Twinrix Junior Group | Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. | 0 Subjects |
Secondary
Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value.
Anti-HAV antibody cut-off value assessed was \>= 15 milli-International Units per milliliter (mIU/mL). Note: Since none of the subjects were seronegative for anti-HAV antibody concentration at the pre-challenge time point, subjects received only the HBV vaccine as the challenge dose.
Time frame: Before (PRE) the challenge dose
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Adult Group | Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value. | 8 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value. | 11 Subjects |
Secondary
Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values
Anti-HBs antibody cut-off values assessed were \>= 6.2 mIU/mL and \>= 10 mIU/mL
Time frame: Before (PRE) and one month after (POST) the challenge dose
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Adult Group | Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | POST [6.2 mIU/mL] (N = 8;11) | 8 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | PRE [10 mIU/mL] (N = 8;11) | 0 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | POST [10 mIU/mL] (N = 8;11) | 8 Subjects |
| Twinrix Adult Group | Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | PRE [6.2 mIU/mL] (N = 8;11) | 0 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | PRE [6.2 mIU/mL] (N = 8;11) | 2 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | POST [6.2 mIU/mL] (N = 8;11) | 11 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | POST [10 mIU/mL] (N = 8;11) | 10 Subjects |
| Twinrix Junior Group | Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values | PRE [10 mIU/mL] (N = 8;11) | 1 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs).
Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: One month after the administration of the challenge dose (Month 0 to Month 1)
Population: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Adult Group | Number of Subjects With Serious Adverse Events (SAEs). | 1 Subjects |
| Twinrix Junior Group | Number of Subjects With Serious Adverse Events (SAEs). | 0 Subjects |