Hepatitis A, Hepatitis B
Conditions
Keywords
Immune memory, Combined hepatitis A and B vaccine, > 41 years old
Brief summary
Only subjects who participated in the primary study will be invited to participate in the extension phase and the challenge dose phase of this study.
Interventions
BIOLOGICALTwinrix
Intramuscular injection, single dose in left deltoid.
BIOLOGICALEngerix-B
Intramuscular injection, single dose in left deltoid.
BIOLOGICALHavrix
Intramuscular injection, single dose in right deltoid.
BIOLOGICALHBVAXPRO
Intramuscular injection, single dose in the left deltoid.
BIOLOGICALVaqta
Intramuscular injection, single dose in right deltoid.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
41 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol. * A male or female who completed the primary vaccination phase of the HAB-160 study (NCT 00603252). * Written informed consent obtained from the subject. * If the subject is female, she must be of non-childbearing potential; 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 the time of study entry. If any apply, the subject must not be included in the study: * Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the challenge dose, or planned use during the study period. * History of any hepatitis A or hepatitis B vaccination or infection since the primary vaccination study. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Acute disease at the time of enrolment. * Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies | One month after the challenge dose. | Anamnestic response was defined as: * for initially seronegative subjects, antibody concentration greater than or equal the cut-off \[≥ 15 Milli-International Units per Milliliter (mIU/mL)\], * for initially seropositive subjects with pre-vaccination antibody, concentration \< 100 mIU/mL: antibody concentration at least four times the pre-vaccination antibody concentration, * for initially seropositive subjects with pre-vaccination antibody concentration ≥ 100 mIU/mL: antibody concentration at least two times the pre-vaccination antibody concentration. |
| Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies | One month after the challenge dose. | Anamnestic response was defined as : * for initially seronegative subjects, antibody concentration ≥ 10 Milli-International Units per Milliliter (mIU/mL), * for initially seropositive subjects: antibody concentration at ≥ 4 fold the pre-vaccination antibody concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Unsolicited Symptoms | During the 31-day follow-up period after the challenge dose. | Unsolicited symptoms = any adverse event (AE) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. |
| Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Prior to administration of challenge dose | Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | During one month following the administration of the challenge dose | A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B. |
| Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination | Since the last study visit of the primary study long-term follow-up study up to challenge dose administration (1 year) | A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B. |
| Number of Subjects Reporting Solicited Symptoms | During the 4-day follow-up period after the challenge dose. | Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache and temperature (above 37 degree Celsius). |
Countries
Belgium, Czechia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Twinrix Group Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix). | 172 |
| Engerix + Havrix Group Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix). | 170 |
| HB VAX PRO + Vaqta Group Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta). | 164 |
| Total | 506 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Alcoholic dependance | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Twinrix Group | Engerix + Havrix Group | HB VAX PRO + Vaqta Group | Total |
|---|---|---|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 8.7 | 59.5 years STANDARD_DEVIATION 10.18 | 59.1 years STANDARD_DEVIATION 9.16 | 59.0 years STANDARD_DEVIATION 9.36 |
| Sex: Female, Male Female | 85 Participants | 83 Participants | 85 Participants | 253 Participants |
| Sex: Female, Male Male | 87 Participants | 87 Participants | 79 Participants | 253 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 | 76 / 172 | 57 / 170 | 75 / 164 |
| serious Total, serious adverse events | 1 / 172 | 2 / 170 | 0 / 164 |
Outcome results
Primary
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies
Anamnestic response was defined as: * for initially seronegative subjects, antibody concentration greater than or equal the cut-off \[≥ 15 Milli-International Units per Milliliter (mIU/mL)\], * for initially seropositive subjects with pre-vaccination antibody, concentration \< 100 mIU/mL: antibody concentration at least four times the pre-vaccination antibody concentration, * for initially seropositive subjects with pre-vaccination antibody concentration ≥ 100 mIU/mL: antibody concentration at least two times the pre-vaccination antibody concentration.
Time frame: One month after the challenge dose.
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies | 164 Participants |
| Engerix + Havrix Group | Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies | 164 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies | 162 Participants |
Primary
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies
Anamnestic response was defined as : * for initially seronegative subjects, antibody concentration ≥ 10 Milli-International Units per Milliliter (mIU/mL), * for initially seropositive subjects: antibody concentration at ≥ 4 fold the pre-vaccination antibody concentration.
Time frame: One month after the challenge dose.
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies | 156 Participants |
| Engerix + Havrix Group | Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies | 148 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies | 136 Participants |
Secondary
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.
Time frame: Prior to administration of challenge dose
Population: Analysis was performed on the Long-Term According-to-Protocol (LT ATP) cohort for analysis of immunogenicity.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | anti-HAV | 212.2 mIU/mL |
| Twinrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | anti-HBs | 40.3 mIU/mL |
| Engerix + Havrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | anti-HAV | 175.4 mIU/mL |
| Engerix + Havrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | anti-HBs | 26.7 mIU/mL |
| HB VAX PRO + Vaqta Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | anti-HAV | 308.4 mIU/mL |
| HB VAX PRO + Vaqta Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | anti-HBs | 15.4 mIU/mL |
Secondary
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.
Time frame: Two weeks and one month after the challenge dose
Population: Analysis was performed on the Log-Term According-to-Protocol (LT ATP) cohort for analysis of immunogenicity.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Twinrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HBs (at Day 14) | 8936.9 mIU/mL |
| Twinrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HAV (at Day 30) | 4062.0 mIU/mL |
| Twinrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HAV (at Day 14) | 2255.0 mIU/mL |
| Twinrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HBs (at Day 30) | 7233.7 mIU/mL |
| Engerix + Havrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HAV (at Day 30) | 3124.1 mIU/mL |
| Engerix + Havrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HAV (at Day 14) | 1774.3 mIU/mL |
| Engerix + Havrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HBs (at Day 30) | 1242.5 mIU/mL |
| Engerix + Havrix Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HBs (at Day 14) | 1521.0 mIU/mL |
| HB VAX PRO + Vaqta Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HAV (at Day 14) | 2712.9 mIU/mL |
| HB VAX PRO + Vaqta Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HBs (at Day 30) | 1075.1 mIU/mL |
| HB VAX PRO + Vaqta Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HBs (at Day 14) | 1222.4 mIU/mL |
| HB VAX PRO + Vaqta Group | Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations | Anti-HAV (at Day 30) | 7481.6 mIU/mL |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.
Time frame: During one month following the administration of the challenge dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 1 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 2 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Number of Subjects Reporting Solicited Symptoms
Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache and temperature (above 37 degree Celsius).
Time frame: During the 4-day follow-up period after the challenge dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Twinrix Group | Number of Subjects Reporting Solicited Symptoms | Gastrointestinal symptoms | 5 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Symptoms | Headache | 21 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Symptoms | Redness | 22 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Symptoms | Temperature | 2 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Symptoms | Pain | 42 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 9 Participants |
| Twinrix Group | Number of Subjects Reporting Solicited Symptoms | Fatigue | 29 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Solicited Symptoms | Gastrointestinal symptoms | 8 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Solicited Symptoms | Fatigue | 24 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Solicited Symptoms | Headache | 20 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 3 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Solicited Symptoms | Pain | 35 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Solicited Symptoms | Temperature | 0 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Solicited Symptoms | Redness | 10 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Solicited Symptoms | Temperature | 2 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Solicited Symptoms | Pain | 46 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Solicited Symptoms | Redness | 19 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 12 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Solicited Symptoms | Gastrointestinal symptoms | 5 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Solicited Symptoms | Headache | 18 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Solicited Symptoms | Fatigue | 28 Participants |
Secondary
Number of Subjects Reporting Unsolicited Symptoms
Unsolicited symptoms = any adverse event (AE) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Time frame: During the 31-day follow-up period after the challenge dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects Reporting Unsolicited Symptoms | 28 Participants |
| Engerix + Havrix Group | Number of Subjects Reporting Unsolicited Symptoms | 10 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects Reporting Unsolicited Symptoms | 21 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination
A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.
Time frame: Since the last study visit of the primary study long-term follow-up study up to challenge dose administration (1 year)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Twinrix Group | Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination | 0 Participants |
| Engerix + Havrix Group | Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination | 0 Participants |
| HB VAX PRO + Vaqta Group | Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination | 0 Participants |