Hepatitis A, Hepatitis B
Conditions
Keywords
Hepatitis A, Hepatitis B, TWINRIX™ ADULT
Brief summary
The aim of this study is to evaluate the long-term persistence of hepatitis A and B antibodies at Years 6, 7, 8, 9 and 10 after subjects received their first two doses primary vaccination schedule of combined hepatitis A/hepatitis B vaccine. This protocol posting deals with objectives & outcome measures of the extension phase at year 6 through to 10. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed description
To evaluate the long-term antibody persistence, volunteers will be bled at Years 6, 7, 8, 9 and 10 after the first vaccine dose of the primary vaccination course to determine their anti-HAV and anti-HBs antibody concentrations. If a subject has become seronegative for anti-HAV antibodies or lost anti-HBs seroprotection concentrations at the long-term blood sampling time point (i.e. Years 6, 7, 8, 9 or 10), he/ she will be offered an additional vaccine dose.
Interventions
BIOLOGICALTWINRIX™ ADULT
2 doses IM injection in primary study
BIOLOGICALEngerix TM
If a subject has become seronegative for anti-HAV antibodies or lost anti-HBs seroprotection concentrations at the long-term blood sampling time point (i.e. Years 6, 7, 8, 9 or 10), he/ she will be offered an additional vaccine dose.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects participating in this study should have participated in the primary study with combined hepatitis A/ hepatitis B vaccine. * 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 |
|---|---|---|
| Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Years 6, 7, 8, 9, and 10. | — |
| Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | At Year 6, 7, 8, 9 and 10 | — |
| Number of Subjects With Immune Response to the Additional Dose of Engerix™-B | One month after the additional dose administration | Immune response was defined as: * anti-hepatitis B surface antigen (anti-HBs) antibody concentration equal or above to 10 milli-international units per milliliter (mIU/mL) at 1 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 1 month post-challenge dose in subjects seropositive at the pre-challenge time-points. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy | At Year 6, 7, 8, 9 and 10 | Serious adverse events (SAEs) assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
| Number of Subjects Reporting Solicited Local and General Symptoms | During the 4-day follow-up period after additional dose | Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache. |
| Number of Subjects Reporting Unsolicited Adverse Events | During the 30-day follow-up period after additional dose | Unsolicited adverse event (AE) covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | During the 30-day follow-up period after additional dose | Serious adverse events (SAEs) assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
Countries
Belgium
Participant flow
Recruitment details
All subjects enrolled in the primary study (208127/076) were invited to come back for the long-term follow-up visits at Year 6 to 10. The enrollment in the protocol section reflects the amount of subjects who came back at year 6. At follow up timepoints less subjects came back.
Pre-assignment details
25 subjects lost seroprotective concentrations for anti-HBs antibodies at blood sampling time-points Years 6 to 10 and were offered an additional dose of Engerix™-B after Year 10 (additional dose phase). These subjects are presented in separate sub-groups for analysis purposes while as per study protocol, the single experimental group is Twinrix.
Participants by arm
| Arm | Count |
|---|---|
| Twinrix Group Subjects who received 2 doses (at Day 0 and Month 6) of Twinrix™ in the primary study (study 208127/076) | 178 |
| Total | 178 |
Baseline characteristics
| Characteristic | Twinrix Group |
|---|---|
| Age, Continuous | 13.1 years STANDARD_DEVIATION 2.82 |
| Sex: Female, Male Female | 91 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 19 | 0 / 0 | 3 / 6 |
| serious Total, serious adverse events | 0 / 19 | 0 / 0 | 0 / 6 |
Outcome results
Primary
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration
Time frame: Years 6, 7, 8, 9, and 10.
Population: The analysis was performed on the long-term (LT) according to protocol (ATP) cohort for immunogenicity.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 6 (n=142) | 692.3 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 7 (n=136) | 753.6 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 8 (n=132) | 544.4 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 9 (n=121) | 479.5 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Year 10 (n=120) | 601.6 milli-international units per milliliter |
Primary
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration
Time frame: At Year 6, 7, 8, 9 and 10
Population: The analysis was performed on the long-term (LT) according to protocol (ATP) cohort for immunogenicity.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 6 (n= 142) | 206.2 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 7 (n= 136) | 157.5 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 8 (n= 132) | 102.7 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 9 (n = 121) | 89.1 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Year 10 (n= 120) | 80.7 milli-international units per milliliter |
Primary
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration
Time frame: Before and 1 month after the additional dose administration
Population: The analysis was performed on the total vaccinated cohort for the additional dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Pre-vaccination | 10.4 milli-international units per milliliter |
| Twinrix Group | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | 1 month after vaccination | 1431.9 milli-international units per milliliter |
| Engerix-B Additional Dose (Pediatric) | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | Pre-vaccination | 8.7 milli-international units per milliliter |
| Engerix-B Additional Dose (Pediatric) | Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration | 1 month after vaccination | 565.9 milli-international units per milliliter |
Primary
Number of Subjects Reporting Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: During the 30-day follow-up period after additional dose
Population: The analysis was performed on the total vaccinated cohort for the additional dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 Participants |
Primary
Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy
Serious adverse events (SAEs) assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: At Year 6, 7, 8, 9 and 10
Population: The analysis was performed on the long-term (LT) total vaccinated cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy | Year 6 (n= 178) | 0 Participants |
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy | Year 7 (n= 175) | 0 Participants |
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy | Year 8 (n= 174) | 0 Participants |
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy | Year 9 (n= 173) | 0 Participants |
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) Assessed by the Investigator as Causally Related to Primary Vaccination, Study Procedures or Lack of Vaccine Efficacy | Year 10 (n= 171) | 0 Participants |
Primary
Number of Subjects Reporting Solicited Local and General Symptoms
Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache.
Time frame: During the 4-day follow-up period after additional dose
Population: The analysis was performed on the total vaccinated cohort for the additional dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Reporting Solicited Local and General Symptoms | Swelling | 1 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Local and General Symptoms | Fever | 0 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Local and General Symptoms | Redness | 2 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Local and General Symptoms | Gastrointestinal symptoms | 2 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Local and General Symptoms | Fatigue | 2 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Local and General Symptoms | Headache | 3 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Local and General Symptoms | Pain | 6 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Solicited Local and General Symptoms | Headache | 0 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Solicited Local and General Symptoms | Pain | 3 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Solicited Local and General Symptoms | Redness | 1 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Solicited Local and General Symptoms | Swelling | 0 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Solicited Local and General Symptoms | Fatigue | 3 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Solicited Local and General Symptoms | Fever | 1 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Solicited Local and General Symptoms | Gastrointestinal symptoms | 1 Participants |
Primary
Number of Subjects Reporting Unsolicited Adverse Events
Unsolicited adverse event (AE) covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time frame: During the 30-day follow-up period after additional dose
Population: The analysis was performed on the total vaccinated cohort for the additional dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Unsolicited Adverse Events | 1 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects Reporting Unsolicited Adverse Events | 1 Participants |
Primary
Number of Subjects With Immune Response to the Additional Dose of Engerix™-B
Immune response was defined as: * anti-hepatitis B surface antigen (anti-HBs) antibody concentration equal or above to 10 milli-international units per milliliter (mIU/mL) at 1 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 1 month post-challenge dose in subjects seropositive at the pre-challenge time-points.
Time frame: One month after the additional dose administration
Population: The analysis was performed on the total vaccinated cohort for the additional dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects With Immune Response to the Additional Dose of Engerix™-B | 19 Participants |
| Engerix-B Additional Dose (Pediatric) | Number of Subjects With Immune Response to the Additional Dose of Engerix™-B | 6 Participants |