Hepatitis A, Hepatitis B
Conditions
Keywords
Hepatitis A, Hepatitis B
Brief summary
This study will evaluate the persistence of the immune response to HAV (Hepatitis A Virus) antigens and HBs (Hepatitis B surface) antigens in healthy adults previously vaccinated with GlaxoSmithKline (GSK) Biologicals' Twinrix Adult. The subjects will be invited for blood sampling 16, 17, 18, 19 and 20 years after vaccination to evaluate the antibody persistence. For subjects in whom low circulating antibodies are detected, the presence of immune memory against hepatitis A & B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine (Havrix and/or Engerix-B) at the next planned visit. No new subjects will be recruited during this study.
Interventions
PROCEDUREBlood sampling
Blood sampling at Year 16, 17, 18, 19 and 20 and at the time of challenge dose administration and 14 days and one month after challenge dose administration (if challenge dose needed).
BIOLOGICALEngerix-B
Engerix-B will be administered to subjects who are not seroprotected against hepatitis B
BIOLOGICALHavrix
Havrix will be administered to subjects who are seronegative for anti-HAV antibodies
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
All subjects must satisfy the following criteria at entry into each of the long-term follow-up visits: * 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 in the primary study Hepatitis A and B vaccine (HAB), HAB-028 (208127/021). * Written informed consent obtained from the subject. All subjects must satisfy the following criteria at entry into the challenge dose phase: * Subjects who the investigator believes that they can and will comply with the requirements of the protocol. * A male or female who received the complete primary vaccination course in the primary study HAB-028 (208127/021). * Written informed consent obtained from the subject. * Subjects who participated in the long-term follow-up (LTFU) phase of the HAB-028 (208127/021) study and for whom the antibody concentrations were below the cut-off at the last available follow-up time-point. * 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 for two months after the administration of the challenge dose.
Exclusion criteria
The following criteria should be checked before entry into each of the long-term follow-up visits. If any exclusion criterion applies, the subject must not be included in the study: * Use of any investigational or non-registered product within 30 days prior to blood sampling. * Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine outside the study procedures, since the primary study HAB-028 (208127/021). * History of hepatitis A or hepatitis B infection since the primary study HAB-028 (208127/021). * Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within three months prior to blood sampling. The following criteria should be checked before the challenge dose is administered. If any apply, the subject must not be included in the challenge dose phase: * Use of any investigational or non-registered product within 30 days prior to study start or planned use during the study. * Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine between the last LTFU visit and the challenge dose visit. * History of hepatitis A or hepatitis B infection between the last LTFU visit and the challenge dose visit. * History of anaphylactic reactions following the administration of vaccines. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. * Acute disease and/or fever at the time of enrolment. * Pregnant or lactating female. * Female planning to become pregnant or planning to discontinue contraceptive precautions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | At Years 16, 17, 18, 19 and 20. | Seropositivity for anti-HAV antibodies is defined as antibody concentrations \>= 15 milliinternational units per milliliter (mIU/mL). Seropositivity for anti-HBs antibodies is defined as antibody concentrations \>= 6.2 mIU/mL. |
| Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | At Years 16, 17, 18, 19 and 20. | Concentrations were expressed as GMCs in mIU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Immune Response to the Challenge Vaccine Antigen | Before, 14 days and one month after the challenge dose at Year 19. | None of the subjects received a challenge dose at Years 16, 17, 18 and 20 while, one subject received the challenge dose at Year 19. |
| Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration | At Year 18, 14 days and 30 days post challenge dose (Year 19). | Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL. |
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19. | An unsolicited AE was defined as any AE (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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19. | A serious adverse event was any untoward medical occurrence that: resulted in death, was 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. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. |
Countries
Belgium
Participant flow
Recruitment details
Subjects who entered the study at Years 16, 17, 18, 19 and 20 time points were subjects who completed the primary study and who returned for blood sampling at the considered time point. At Year 19 time point, one subject was given a challenge dose of Engerix.
Participants by arm
| Arm | Count |
|---|---|
| Twinrix Group Pooled group of subjects from groups who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | Twinrix Group |
|---|---|
| Age, Continuous | 39.6 Years STANDARD_DEVIATION 1.4 |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 40 |
Outcome results
Primary
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)
Concentrations were expressed as GMCs in mIU/mL.
Time frame: At Years 16, 17, 18, 19 and 20.
Population: The analysis was performed on the Long-Term (LT) According-to-Protocol (ATP) cohort for analysis of immunogenicity.They were included in the ATP analysis for the primary study, did not receive hepatitis A or B vaccination that was not specified in the protocol and were not eliminated for abnormal increase of antibody concentrations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HAV [at Year 16] (N=23) | 614.2 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HBs [at Year 16] (N=23) | 138.7 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HAV [at Year 17] (N=19) | 479.2 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HBs [at Year 17] (N=19) | 165.1 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HAV [at Year 18] (N=10) | 653.2 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HBs [at Year 18] (N=10) | 278.3 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HAV [at Year 19] (N=17) | 728.7 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HBs [at Year 19] (N=18) | 198.4 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HAV [at Year 20] (N=18) | 511.9 milli-international units per milliliter |
| Twinrix Group | Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs) | anti-HBs [at Year 20] (N=18) | 195.8 milli-international units per milliliter |
Primary
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL)
Seropositivity for anti-HAV antibodies is defined as antibody concentrations \>= 15 milliinternational units per milliliter (mIU/mL). Seropositivity for anti-HBs antibodies is defined as antibody concentrations \>= 6.2 mIU/mL.
Time frame: At Years 16, 17, 18, 19 and 20.
Population: The analysis was performed on the Long-Term (LT) According-to-Protocol (ATP) cohort for analysis of immunogenicity. They were included in the ATP analysis for the primary study, did not receive hepatitis A or B (hep A/B) vaccination that was not specified in the protocol and were not eliminated for abnormal increase of antibody concentrations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | Anti-HAV >=15 mIU/mL [at Year 16] (N=23) | 23 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 6.2 mIU/mL [at Year 16] (N=23) | 20 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 10 mIU/mL [at Year 16] (N=23) | 20 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HAV >= 15 mIU/mL [at Year 17] (N=19) | 19 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 6.2 mIU/mL [at Year 17] (N=19) | 17 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 10 mIU/mL [at Year 17] (N=19) | 17 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HAV >= 15 mIU/mL [at Year 18] (N=10) | 10 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 6.2 mIU/mL [at Year 18] (N=10) | 9 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 10 mIU/mL [at Year 18] (N=10) | 9 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HAV >= 15 mIU/mL [at Year 19] (N=17) | 17 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 6.2 mIU/mL [at Year 19] (N=18) | 17 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 10 mIU/mL [at Year 19] (N=18) | 17 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HAV >= 15 mIU/mL [at Year 20] (N=18) | 18 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 6.2 mIU/mL [at Year 20] (N=18) | 17 Subjects |
| Twinrix Group | Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) | anti-HBs >= 10 mIU/mL [at Year 20] (N=18) | 17 Subjects |
Secondary
Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration
Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL.
Time frame: At Year 18, 14 days and 30 days post challenge dose (Year 19).
Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration | [Subject 1; 30 days post challenge dose] | 12736.00 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration | [Subject 1; at year 18] | 13.26 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration | [Subject 1; 14 days post challenge dose] | 21926.00 milli-international units per milliliter |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event is any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, or was a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Time frame: Up to Year 20.
Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event was any untoward medical occurrence that: resulted in death, was 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. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Time frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.
Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 Subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AE)
An unsolicited AE was defined as any AE (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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Time frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.
Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 1 Subjects |
Secondary
Number of Subjects With Immune Response to the Challenge Vaccine Antigen
None of the subjects received a challenge dose at Years 16, 17, 18 and 20 while, one subject received the challenge dose at Year 19.
Time frame: Before, 14 days and one month after the challenge dose at Year 19.
Population: The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Twinrix Group | Number of Subjects With Immune Response to the Challenge Vaccine Antigen | 1 Subjects |