Hepatitis B
Conditions
Keywords
Persistence, Hepatitis B vaccine
Brief summary
To evaluate the persistence of antibodies against hepatitis B at 30, 42, 54 and 66 months after the first dose of the hepatitis B primary vaccination course. Subjects were aged 11 to 15 years at the time of the primary vaccination course. At the time of enrollment in the present long-term follow-up study subjects were aged 13 to 18 years. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed description
All subjects who participated in the primary study, in which they received either 2 or 3 doses of GSK Biologicals hepatitis B vaccine, and who consented to participate in the long-term follow-up at Month 42 were contacted by the investigators. No additional subjects will be recruited during this long-term follow-up study and no vaccine will be administered.
Interventions
BIOLOGICALEngerix™-B (thiomersal-free) 20µg
In the primary study: 2 deep intramuscular injections (Months 0, & 6)
BIOLOGICAL10 μg Engerix™-B (preservative-free)
In the primary study: 3 deep intramuscular injections (months 0, 1 & 6)
BIOLOGICALplacebo
In the primary study: 1 deep intramuscular injection (month 1)
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 20 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects have participated in primary study HBV-280 * Written informed consent will be obtained from each subject and/ or parent or guardian of the subject before the blood-sampling visit of each year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | At Month 7 | A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL. |
| Antibody Titers Against Hepatitis-B Virus. | At Month 30, Month 42, Month 54 and Month 66 | Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | During the 4-day (Day 0-3) follow-up period after each vaccination and overall | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. |
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | During the 4-day (Day 0-3) follow-up period after each vaccination and overall | Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, and fever. Any was defined as incidence of the specified symptoms regardless of intensity or relationship to study vaccine. Gastrointestinal symptoms included nausea, vomiting, diarrhea and abdominal pain. Grade 3 fever was defined as fever (axillary temperature) \> 38.5°C. Grade 3 symptoms were defined as symptoms which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the vaccination. |
| Antibody Titers Against Hepatitis-B Virus. | At Months 1, 2, 6 and 7 | Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs. |
| Number of Subjects With Serious Adverse Events (SAEs) | During the entire study period (Month 0 to Month 66) | Serious adverse events (SAEs) assessed include 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. |
| Number of Subjects With Serious Adverse Events (SAEs). | At Month 30, Month 42, Month 54 & Month 66 | erious adverse events (SAEs) assessed include 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. |
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE). | During the 31-day (Day 0-30) follow-up period after each vaccination and overall | 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. |
| Number of Subjects Seroprotected for Anti-HBs Antibody. | At Months 1, 2 and 6 | A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL. |
Countries
Australia, Belgium, Ukraine
Participant flow
Recruitment details
All subjects who participated in the primary vaccination study, in which they received either 2 or 3 doses of GSK Biologicals hepatitis B vaccine, and who consented to participate in the long-term follow-up were contacted by the investigators. No additional subjects were recruited during this long-term follow-up study.
Participants by arm
| Arm | Count |
|---|---|
| 2-dose Engerix subjects received 2 doses of adult (thiomersal-free) HBV formulation, one at 0 and 6 months, respectively and placebo (physiological saline) at 1 month. | 258 |
| 3-dose Engerix subjects received 3 doses of paediatric (preservative-free) HBV formulation one at 0, 1 and 6 months, respectively. | 126 |
| Total | 384 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Primary Study | Lost to Follow-up | 2 | 3 |
| Primary Study | Other | 1 | 0 |
| Primary Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | 2-dose Engerix | 3-dose Engerix | Total |
|---|---|---|---|
| Age, Continuous | 12.9 years STANDARD_DEVIATION 1.23 | 12.7 years STANDARD_DEVIATION 1.32 | 12.8 years STANDARD_DEVIATION 1.26 |
| Sex: Female, Male Female | 132 Participants | 61 Participants | 193 Participants |
| Sex: Female, Male Male | 126 Participants | 65 Participants | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 257 | 0 / 125 |
| other Total, other adverse events | 155 / 257 | 74 / 125 |
| serious Total, serious adverse events | 4 / 257 | 1 / 125 |
Outcome results
Primary
Antibody Titers Against Hepatitis-B Virus.
Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs.
Time frame: At Month 30, Month 42, Month 54 and Month 66
Population: Long Term According-to-Protocol cohort for immunogenicity, including all subjects who returned at the considered follow-up time point and who complied with the protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 2-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 30 (N=140, 64) | 229.0 mIU/mL |
| 2-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 42 (N=166, 80) | 159.7 mIU/mL |
| 2-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 54 (N=147, 76) | 123.6 mIU/mL |
| 2-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 66 (N=132, 70) | 82.1 mIU/mL |
| 3-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 66 (N=132, 70) | 225.2 mIU/mL |
| 3-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 30 (N=140, 64) | 708.3 mIU/mL |
| 3-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 54 (N=147, 76) | 277.6 mIU/mL |
| 3-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 42 (N=166, 80) | 417.9 mIU/mL |
Primary
Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.
A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.
Time frame: At Month 7
Population: The ATP cohort for immunogenicity included all evaluable subjects who had post-vaccination immunogenicity results and who complied with the protocol, including the time schedule for vaccination and blood sample draw.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | 233 Subjects |
| 3-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | 111 Subjects |
Primary
Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.
A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.
Time frame: At Month 30, Month 42, Month 54 and Month 66
Population: Long Term According-to-Protocol cohort for immunogenicity, including all subjects who returned at the considered follow-up time point and who complied with the protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | Month 30 (N=140, 64) | 122 Subjects |
| 2-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | Month 42 (N=166, 80) | 139 Subjects |
| 2-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | Month 54 (N=147, 76) | 124 Subjects |
| 2-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | Month 66 (N=132, 70) | 105 Subjects |
| 3-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | Month 66 (N=132, 70) | 64 Subjects |
| 3-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | Month 30 (N=140, 64) | 62 Subjects |
| 3-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | Month 54 (N=147, 76) | 72 Subjects |
| 3-dose Engerix | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. | Month 42 (N=166, 80) | 74 Subjects |
Secondary
Antibody Titers Against Hepatitis-B Virus.
Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs.
Time frame: At Months 1, 2, 6 and 7
Population: The ATP cohort for immunogenicity included all evaluable subjects who had post-vaccination immunogenicity results and who complied with the protocol, including the time schedule for vaccination and blood sample draw.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 2-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 6 (N=239, 113) | 18.8 mIU/mL |
| 2-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 2 (N=240, 113) | 17.6 mIU/mL |
| 2-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 7 (N=241, 113) | 2738.5 mIU/mL |
| 2-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 1 (N=240, 112) | 28.8 mIU/mL |
| 3-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 7 (N=241, 113) | 7238.3 mIU/mL |
| 3-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 2 (N=240, 113) | 29.4 mIU/mL |
| 3-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 6 (N=239, 113) | 90.0 mIU/mL |
| 3-dose Engerix | Antibody Titers Against Hepatitis-B Virus. | Month 1 (N=240, 112) | 28.7 mIU/mL |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE).
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.
Time frame: During the 31-day (Day 0-30) follow-up period after each vaccination and overall
Population: Total Cohort included all enrolled (i.e. randomized or vaccinated) subjects who received at least one vaccine dose and for whom data were available. No information regarding AEs was available for 1 subject in each group
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2-dose Engerix | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE). | any AE(s) | 112 Subjects |
| 2-dose Engerix | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE). | grade 3 AE(s) | 31 Subjects |
| 2-dose Engerix | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE). | related AE(s) | 9 Subjects |
| 3-dose Engerix | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE). | any AE(s) | 54 Subjects |
| 3-dose Engerix | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE). | grade 3 AE(s) | 15 Subjects |
| 3-dose Engerix | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE). | related AE(s) | 1 Subjects |
Secondary
Number of Subjects Seroprotected for Anti-HBs Antibody.
A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.
Time frame: At Months 1, 2 and 6
Population: The ATP cohort for immunogenicity included all evaluable subjects who had post-vaccination immunogenicity results and who complied with the protocol, including the time schedule for vaccination and blood sample draw.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2-dose Engerix | Number of Subjects Seroprotected for Anti-HBs Antibody. | Month 1 (N=240, 112) | 31 Subjects |
| 2-dose Engerix | Number of Subjects Seroprotected for Anti-HBs Antibody. | Month 2 (N=240, 113) | 27 Subjects |
| 2-dose Engerix | Number of Subjects Seroprotected for Anti-HBs Antibody. | Month 6 (N=239, 113) | 63 Subjects |
| 3-dose Engerix | Number of Subjects Seroprotected for Anti-HBs Antibody. | Month 1 (N=240, 112) | 8 Subjects |
| 3-dose Engerix | Number of Subjects Seroprotected for Anti-HBs Antibody. | Month 2 (N=240, 113) | 63 Subjects |
| 3-dose Engerix | Number of Subjects Seroprotected for Anti-HBs Antibody. | Month 6 (N=239, 113) | 99 Subjects |
Secondary
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
Time frame: During the 4-day (Day 0-3) follow-up period after each vaccination and overall
Population: The ATP cohort for safety included all evaluable subjects, who received at least one dose of study vaccine according to their random assignment, with sufficient data to perform safety analysis, who did not receive a vaccine not specified or forbidden in the protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain; Dose 2 (N=252, 119) | 42 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain; Dose 1 (N=253, 121) | 6 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness; Dose 1 (N=253, 121) | 30 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness; Dose 1 (N=253, 121) | 0 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling; Dose 1 (N=253, 121) | 18 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling; Dose 1 (N=253, 121) | 2 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain; Dose 1 (N=253, 121) | 121 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain; Dose 2 (N=252, 119) | 3 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness; Dose 2 (N=252, 119) | 15 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness; Dose 2 (N=252, 119) | 1 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling; Dose 2 (N=252, 119) | 8 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling; Dose 2 (N=252, 119) | 1 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain; Dose 3 (N=250, 118) | 106 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain; Dose 3 (N=250, 118) | 4 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness; Dose 3 (N=250, 118) | 29 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness; Dose 3 (N=250, 118) | 0 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling; Dose 3 (N=250, 118) | 14 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling; Dose 3 (N=250, 118) | 0 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain; Across Doses (N=253, 121) | 155 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain; Across Doses (N=253, 121) | 8 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness; Across Doses (N=253, 121) | 50 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness; Across Doses (N=253, 121) | 0 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling; Across Doses (N=253, 121) | 27 Subjects |
| 2-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling; Across Doses (N=253, 121) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling; Across Doses (N=253, 121) | 15 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain; Dose 1 (N=253, 121) | 44 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain; Dose 3 (N=250, 118) | 35 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain; Dose 1 (N=253, 121) | 3 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain; Across Doses (N=253, 121) | 74 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness; Dose 1 (N=253, 121) | 10 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain; Dose 3 (N=250, 118) | 1 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness; Dose 1 (N=253, 121) | 1 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness; Across Doses (N=253, 121) | 1 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling; Dose 1 (N=253, 121) | 8 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness; Dose 3 (N=250, 118) | 11 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling; Dose 1 (N=253, 121) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain; Across Doses (N=253, 121) | 6 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain; Dose 2 (N=252, 119) | 38 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness; Dose 3 (N=250, 118) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain; Dose 2 (N=252, 119) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling; Across Doses (N=253, 121) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness; Dose 2 (N=252, 119) | 15 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling; Dose 3 (N=250, 118) | 6 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness; Dose 2 (N=252, 119) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness; Across Doses (N=253, 121) | 28 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling; Dose 2 (N=252, 119) | 5 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling; Dose 3 (N=250, 118) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling; Dose 2 (N=252, 119) | 0 Subjects |
Secondary
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, and fever. Any was defined as incidence of the specified symptoms regardless of intensity or relationship to study vaccine. Gastrointestinal symptoms included nausea, vomiting, diarrhea and abdominal pain. Grade 3 fever was defined as fever (axillary temperature) \> 38.5°C. Grade 3 symptoms were defined as symptoms which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the vaccination.
Time frame: During the 4-day (Day 0-3) follow-up period after each vaccination and overall
Population: The ATP cohort for safety included all evaluable subjects, who received at least one dose of study vaccine according to their random assignment, with sufficient data to perform safety analysis, who did not receive a vaccine not specified or forbidden in the protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue; Dose 2 (N=252, 119) | 37 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue; Dose 1 (N=253, 121) | 1 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue; Dose 1 (N=253, 121) | 29 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal; Dose 1 (N=253, 121) | 26 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal; Dose 1 (N=253, 121) | 3 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal; Dose 1 (N=253, 121) | 11 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Headache; Dose 1 (N=253, 121) | 57 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache; Dose 1 (N=253, 121) | 0 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Headache; Dose 1 (N=253, 121) | 33 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Dose 1 (N=253, 121) | 4 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Dose 1 (N=253, 121) | 0 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Dose 1 (N=253, 121) | 3 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue; Dose 1 (N=253, 121) | 50 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue; Dose 2 (N=252, 119) | 2 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue; Dose 2 (N=252, 119) | 23 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal; Dose 2 (N=252, 119) | 20 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal; Dose 2 (N=252, 119) | 0 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal; Dose 2 (N=252, 119) | 7 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Headache; Dose 2 (N=252, 119) | 40 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache; Dose 2 (N=252, 119) | 0 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Headache; Dose 2 (N=252, 119) | 24 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Dose 2 (N=252, 119) | 5 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Dose 2 (N=252, 119) | 1 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Dose 2 (N=252, 119) | 5 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue; Dose 3 (N=250, 118) | 49 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue; Dose 3 (N=250, 118) | 3 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue; Dose 3 (N=250, 118) | 30 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal; Dose 3 (N=250, 118) | 17 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal; Dose 3 (N=250, 118) | 3 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal; Dose 3 (N=250, 118) | 6 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Headache; Dose 3 (N=250, 118) | 36 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache; Dose 3 (N=250, 118) | 1 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Headache; Dose 3 (N=250, 118) | 22 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Dose 3 (N=250, 118) | 13 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Dose 3 (N=250, 118) | 1 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Dose 3 (N=250, 118) | 7 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue; Across Doses (N=253, 121) | 77 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue; Across Doses (N=253, 121) | 4 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue; Across Doses (N=253, 121) | 51 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal; Across Doses (N=253, 121) | 36 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal; Across Doses (N=253,121) | 6 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal; Across Doses (N=253,121) | 17 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Headache; Across Doses (N=253, 121) | 78 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache; Across Doses (N=253, 121) | 1 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Headache; Across Doses (N=253, 121) | 49 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Across Doses (N=253, 121) | 17 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Across Doses (N=253, 121) | 1 Subjects |
| 2-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Across Doses (N=253, 121) | 10 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Across Doses (N=253, 121) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue; Dose 1 (N=253, 121) | 26 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue; Dose 3 (N=250, 118) | 20 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue; Dose 1 (N=253, 121) | 1 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue; Across Doses (N=253, 121) | 46 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue; Dose 1 (N=253, 121) | 16 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue; Dose 3 (N=250, 118) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal; Dose 1 (N=253, 121) | 4 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Headache; Across Doses (N=253, 121) | 46 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal; Dose 1 (N=253, 121) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue; Dose 3 (N=250, 118) | 8 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal; Dose 1 (N=253, 121) | 3 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue; Across Doses (N=253, 121) | 3 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Headache; Dose 1 (N=253, 121) | 29 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal; Dose 3 (N=250, 118) | 14 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache; Dose 1 (N=253, 121) | 1 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Across Doses (N=253, 121) | 14 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Headache; Dose 1 (N=253, 121) | 15 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal; Dose 3 (N=250, 118) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Dose 1 (N=253, 121) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue; Across Doses (N=253, 121) | 30 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Dose 1 (N=253, 121) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal; Dose 3 (N=250, 118) | 6 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Dose 1 (N=253, 121) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache; Across Doses (N=253, 121) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Fatigue; Dose 2 (N=252, 119) | 18 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Headache; Dose 3 (N=250, 118) | 20 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Fatigue; Dose 2 (N=252, 119) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal; Across Doses (N=253, 121) | 21 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Fatigue; Dose 2 (N=252, 119) | 13 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache; Dose 3 (N=250, 118) | 1 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Gastrointestinal; Dose 2 (N=252, 119) | 7 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Across Doses (N=253, 121) | 10 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal; Dose 2 (N=252, 119) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Headache; Dose 3 (N=250, 118) | 12 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal; Dose 2 (N=252, 119) | 5 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Gastrointestinal; Across Doses (N=253,121) | 2 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Headache; Dose 2 (N=252, 119) | 21 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Dose 3 (N=250, 118) | 9 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Headache; Dose 2 (N=252, 119) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Headache; Across Doses (N=253, 121) | 30 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Headache; Dose 2 (N=252, 119) | 11 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Dose 3 (N=250, 118) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Dose 2 (N=252, 119) | 5 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Gastrointestinal; Across Doses (N=253,121) | 14 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Dose 2 (N=252, 119) | 0 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Dose 3 (N=250, 118) | 5 Subjects |
| 3-dose Engerix | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Dose 2 (N=252, 119) | 4 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include 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: During the entire study period (Month 0 to Month 66)
Population: Total Cohort included all enrolled (i.e. randomized or vaccinated) subjects who received at least one vaccine dose and for whom data were available. No information regarding AEs was available for 1 subject in each group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs) | 4 Subjects |
| 3-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs) | 1 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs).
erious adverse events (SAEs) assessed include 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: At Month 30, Month 42, Month 54 & Month 66
Population: LT total cohort included all subjects who were included in the total cohort in the primary study and returned at the considered follow-up time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs). | Month 30 (N=179, 88) | 0 Participants |
| 2-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs). | Month 42 (N=174, 84) | 0 Participants |
| 2-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs). | Month 54 (N=166, 79) | 0 Participants |
| 2-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs). | Month 66 (N=158, 76) | 0 Participants |
| 3-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs). | Month 66 (N=158, 76) | 0 Participants |
| 3-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs). | Month 30 (N=179, 88) | 0 Participants |
| 3-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs). | Month 54 (N=166, 79) | 0 Participants |
| 3-dose Engerix | Number of Subjects With Serious Adverse Events (SAEs). | Month 42 (N=174, 84) | 0 Participants |