Hepatitis A Vaccine
Conditions
Keywords
Havrix, Cross-sectional seroprevalence survey, Panama, Long-term persistence, Hepatitis
Brief summary
The purpose of this study is to evaluate the persistence of hepatitis A antibodies, approximately 8 years and 10 years post vaccination with the complete series of Havrix (2 doses) and the partial series completion (1 dose).
Detailed description
The study comprises of two independent cross-sectional surveys (Year 8 and Year 10). The first cross-sectional serosurvey will evaluate the long term persistence of immunity approximately 8 years post vaccine administration and the second cross-sectional study will evaluate long term persistence, approximately 10 years post vaccine administration.
Interventions
OTHERBlood sample collection
A blood sample (\ 5mL) will be collected from all subjects at each cross-sectional survey (Year 8 and Year 10).
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 15 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects whose parent(s)/ LAR(s), in the opinion of the investigator, can and will comply with the requirements of the protocol. * Written informed assent/consent obtained from the subject or subject's parent(s)/ LAR(s) of the subject. * Available HAV vaccination records. * Children who have received either 1 or two doses of Havrix at selected health centres of Panama. * Children with ≥ 7 years and \< 10 years between last dose and Persistence Visit 1 (Year 8) and children ≥ 10 years and \< 13 years between last dose and Persistence Visit 1' (Year 10).
Exclusion criteria
* Child in care. * Subjects with history of vaccination with other hepatitis A vaccines other than Havrix. * Subjects with known past history of hepatitis A infection, both without vaccination and after they received the last dose of Havrix (1 dose or the complete 2 dose schedule).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-hepatitis A Virus (HAV) Seropositivity Status at Approximately 8 Years Following Last Administered Havrix Dose | At approximately 8 years after the last administered vaccine dose | Subjects are defined as being seropositive if their anti-HAV antibody concentration is equal to or above (≥) 15 milli-international unit/milliliter (mIU/mL). |
| Number of Subjects With Anti-HAV Seropositivity Status at Approximately 10 Years Following Last Administered Havrix Dose | At approximately 10 years after the last administered vaccine dose | Subjects are defined as being seropositive if their anti-HAV antibody concentration is equal to or above (≥) 15 mIU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HAV Antibody Concentrations at Approximately 10 Years Following Last Administered Havrix Dose | At approximately 10 years after the last administered vaccine dose | Anti-HAV antibody concentrations were measured by ELISA, expressed as GMCs, in mIU/mL. The cut-off of the assay was an anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL. |
| Anti-HAV Antibody Concentrations at Approximately 8 Years Following Last Administered Havrix Dose | At approximately 8 years after the last administered vaccine dose | Anti-HAV antibody concentrations were measured by ELISA, expressed as GMCs, in mIU/mL. The cut-off of the assay was an anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL. |
| Number of Subjects With Anti-HAV Antibody Concentration ≥ 15 mIU/mL at Approximately 8 Years Following Last Administered Havrix Dose - Exploration of Non-inferiority of the 1-dose Schedule Compared to the 2-dose Schedule of Havrix | At approximately 8 years after the last administered vaccine dose | Subjects are defined as being seropositive if their anti-HAV antibody concentration is equal to or above (≥) 15 mIU/mL. |
| Number of Subjects With Anti-HAV Antibody Concentrations ≥ 15 mIU/mL at Approximately 10 Years Following Last Administered Havrix Dose - Exploration of Non-inferiority of the 1-dose Schedule Compared to the 2-dose Schedule of Havrix | At approximately 10 years after the last administered vaccine dose | Subjects are defined as being seropositive if their anti-HAV antibody concentration is equal to or above (≥) 15 mIU/mL. |
Countries
Panama
Participant flow
Recruitment details
The study was conducted at 4 centers in Panama. Out of the 1201 subjects originally enrolled in the study, 2 subjects were eliminated from the ATP cohort for persistence, due to non-eligibility. Hence, 1199 subjects were included in the ATP cohort for persistence.
Pre-assignment details
The design of the study included 2 epochs: Epoch 001 - Persistence at Year 8 and Epoch 002 - Persistence at Year 10.
Participants by arm
| Arm | Count |
|---|---|
| Havrix 1 dose_Year 8 Group Subjects who received one dose of Havrix vaccine and with more than or equal to (≥) 7 years and less than (\<) 10 years between the administration of the vaccine dose and the Persistence Visit at Year 8 and who participated in the Year 8 cross-sectional survey. | 300 |
| Havrix 2 doses_Year 8 Group Subjects who received two doses of Havrix vaccine and with more than or equal to (≥) 7 years and less than (\<) 10 years between the administration of the last vaccine dose and the Persistence Visit at Year 8 and who participated in the Year 8 cross-sectional survey. | 300 |
| Havrix 1 dose_Year 10 Group Subjects who received one dose of Havrix vaccine and with more than or equal to (≥) 10 years and less than (\<) 13 years between the administration of the vaccine dose and the Persistence Visit at Year 10 and who participated in the Year 10 cross-sectional survey. | 299 |
| Havrix 2 doses_Year 10 Group Subjects who received two doses of Havrix vaccine and with more than or equal to (≥) 10 years and less than (\<) 13 years between the administration of the vaccine dose and the Persistence Visit at Year 10 and who participated in the Year 10 cross-sectional survey. | 300 |
| Total | 1,199 |
Baseline characteristics
| Characteristic | Total | Havrix 1 dose_Year 8 Group | Havrix 2 doses_Year 10 Group | Havrix 1 dose_Year 10 Group | Havrix 2 doses_Year 8 Group |
|---|---|---|---|---|---|
| Age, Continuous | 12.0 Years STANDARD_DEVIATION 0.5 | 10.5 Years STANDARD_DEVIATION 0.9 | 12.0 Years STANDARD_DEVIATION 0.4 | 12.0 Years STANDARD_DEVIATION 0.5 | 10.0 Years STANDARD_DEVIATION 0.7 |
| Race/Ethnicity, Customized Geographic ancestry African Heritage / African American | 11 Participants | 0 Participants | 6 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Geographic ancestry American Indian or Alaskan Native | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Geographic ancestry Mixed race | 577 Participants | 0 Participants | 290 Participants | 287 Participants | 0 Participants |
| Race/Ethnicity, Customized Geographic ancestry White - Caucasian / European Heritage | 7 Participants | 0 Participants | 3 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Geographic Ancestry African Heritage / African American | 19 Participants | 13 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Geographic Ancestry Mixed Race | 580 Participants | 286 Participants | 0 Participants | 0 Participants | 294 Participants |
| Race/Ethnicity, Customized Geographic Ancestry White - Caucasian / European Heritage | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 296 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 276 Participants | 164 Participants | 138 Participants | 138 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 300 | 0 / 300 | 0 / 299 | 0 / 300 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 300 | 0 / 300 | 0 / 299 | 0 / 300 |
Outcome results
Primary
Number of Subjects With Anti-HAV Seropositivity Status at Approximately 10 Years Following Last Administered Havrix Dose
Subjects are defined as being seropositive if their anti-HAV antibody concentration is equal to or above (≥) 15 mIU/mL.
Time frame: At approximately 10 years after the last administered vaccine dose
Population: The analysis was performed on the ATP cohort for persistence at Year 10, which included all enrolled subjects who had a valid informed consent, had available assay results at Year 10 sero-surveys, had not received other HAV vaccine, with no history HAV infection prior to the study and who had available HAV vaccination records.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Havrix 1 dose_Year 8 Group | Number of Subjects With Anti-HAV Seropositivity Status at Approximately 10 Years Following Last Administered Havrix Dose | Seropositive | 215 Participants |
| Havrix 1 dose_Year 8 Group | Number of Subjects With Anti-HAV Seropositivity Status at Approximately 10 Years Following Last Administered Havrix Dose | Seronegative | 84 Participants |
| Havrix 2 doses_Year 8 Group | Number of Subjects With Anti-HAV Seropositivity Status at Approximately 10 Years Following Last Administered Havrix Dose | Seropositive | 289 Participants |
| Havrix 2 doses_Year 8 Group | Number of Subjects With Anti-HAV Seropositivity Status at Approximately 10 Years Following Last Administered Havrix Dose | Seronegative | 11 Participants |
Primary
Number of Subjects With Anti-hepatitis A Virus (HAV) Seropositivity Status at Approximately 8 Years Following Last Administered Havrix Dose
Subjects are defined as being seropositive if their anti-HAV antibody concentration is equal to or above (≥) 15 milli-international unit/milliliter (mIU/mL).
Time frame: At approximately 8 years after the last administered vaccine dose
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for persistence at Year 8, which included all enrolled subjects who had a valid informed consent, had available assay results at Year 8 sero-surveys, had not received other HAV vaccine, with no history HAV infection prior to the study and who had available HAV vaccination records.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Havrix 1 dose_Year 8 Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Seropositivity Status at Approximately 8 Years Following Last Administered Havrix Dose | Seropositive | 223 Participants |
| Havrix 1 dose_Year 8 Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Seropositivity Status at Approximately 8 Years Following Last Administered Havrix Dose | Seronegative | 77 Participants |
| Havrix 2 doses_Year 8 Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Seropositivity Status at Approximately 8 Years Following Last Administered Havrix Dose | Seropositive | 293 Participants |
| Havrix 2 doses_Year 8 Group | Number of Subjects With Anti-hepatitis A Virus (HAV) Seropositivity Status at Approximately 8 Years Following Last Administered Havrix Dose | Seronegative | 7 Participants |
Secondary
Anti-HAV Antibody Concentrations at Approximately 10 Years Following Last Administered Havrix Dose
Anti-HAV antibody concentrations were measured by ELISA, expressed as GMCs, in mIU/mL. The cut-off of the assay was an anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL.
Time frame: At approximately 10 years after the last administered vaccine dose
Population: The analysis was performed on the ATP cohort for persistence at Year 10, which included all enrolled subjects who had a valid informed consent, had available assay results at Year 10 sero-surveys, had not received other HAV vaccine, with no history HAV infection prior to the study and who had available HAV vaccination records.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Havrix 1 dose_Year 8 Group | Anti-HAV Antibody Concentrations at Approximately 10 Years Following Last Administered Havrix Dose | 26.0 mIU/mL |
| Havrix 2 doses_Year 8 Group | Anti-HAV Antibody Concentrations at Approximately 10 Years Following Last Administered Havrix Dose | 82.1 mIU/mL |
Secondary
Anti-HAV Antibody Concentrations at Approximately 8 Years Following Last Administered Havrix Dose
Anti-HAV antibody concentrations were measured by ELISA, expressed as GMCs, in mIU/mL. The cut-off of the assay was an anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL.
Time frame: At approximately 8 years after the last administered vaccine dose
Population: The analysis was performed on the ATP cohort for persistence at Year 8, which included all enrolled subjects who had a valid informed consent, had available assay results at Year 8 sero-surveys, had not received other HAV vaccine, with no history HAV infection prior to the study and who had available HAV vaccination records.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Havrix 1 dose_Year 8 Group | Anti-HAV Antibody Concentrations at Approximately 8 Years Following Last Administered Havrix Dose | 40.2 mIU/mL |
| Havrix 2 doses_Year 8 Group | Anti-HAV Antibody Concentrations at Approximately 8 Years Following Last Administered Havrix Dose | 123.9 mIU/mL |
Secondary
Number of Subjects With Anti-HAV Antibody Concentration ≥ 15 mIU/mL at Approximately 8 Years Following Last Administered Havrix Dose - Exploration of Non-inferiority of the 1-dose Schedule Compared to the 2-dose Schedule of Havrix
Subjects are defined as being seropositive if their anti-HAV antibody concentration is equal to or above (≥) 15 mIU/mL.
Time frame: At approximately 8 years after the last administered vaccine dose
Population: The analysis was performed on the ATP cohort for persistence at Year 8, which included all enrolled subjects who had a valid informed consent, had available assay results at Year 8 sero-surveys, had not received other HAV vaccine, with no history HAV infection prior to the study and who had available HAV vaccination records.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Havrix 1 dose_Year 8 Group | Number of Subjects With Anti-HAV Antibody Concentration ≥ 15 mIU/mL at Approximately 8 Years Following Last Administered Havrix Dose - Exploration of Non-inferiority of the 1-dose Schedule Compared to the 2-dose Schedule of Havrix | 223 Participants |
| Havrix 2 doses_Year 8 Group | Number of Subjects With Anti-HAV Antibody Concentration ≥ 15 mIU/mL at Approximately 8 Years Following Last Administered Havrix Dose - Exploration of Non-inferiority of the 1-dose Schedule Compared to the 2-dose Schedule of Havrix | 293 Participants |
Comparison: Difference in seropositivity rates for anti-HAV antibody: To demonstrate that 1-dose schedule of Havrix (Havrix 1 dose\_Year 8 Group) was non-inferior to the 2-dose schedule of Havrix (Havrix 2 doses\_Year 8 Group), in terms of seropositivity rates for anti-HAV antibody, measured by ELISA, approximately 8 years after the administration of the last vaccine dose.p-value: <0.000195% CI: [-28.78, -18.29]Fisher Exact
Secondary
Number of Subjects With Anti-HAV Antibody Concentrations ≥ 15 mIU/mL at Approximately 10 Years Following Last Administered Havrix Dose - Exploration of Non-inferiority of the 1-dose Schedule Compared to the 2-dose Schedule of Havrix
Subjects are defined as being seropositive if their anti-HAV antibody concentration is equal to or above (≥) 15 mIU/mL.
Time frame: At approximately 10 years after the last administered vaccine dose
Population: The analysis was performed on the ATP cohort for persistence at Year 10, which included all enrolled subjects who had a valid informed consent, had available assay results at Year 10 sero-surveys, had not received other HAV vaccine, with no history HAV infection prior to the study and who had available HAV vaccination records.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Havrix 1 dose_Year 8 Group | Number of Subjects With Anti-HAV Antibody Concentrations ≥ 15 mIU/mL at Approximately 10 Years Following Last Administered Havrix Dose - Exploration of Non-inferiority of the 1-dose Schedule Compared to the 2-dose Schedule of Havrix | 215 Participants |
| Havrix 2 doses_Year 8 Group | Number of Subjects With Anti-HAV Antibody Concentrations ≥ 15 mIU/mL at Approximately 10 Years Following Last Administered Havrix Dose - Exploration of Non-inferiority of the 1-dose Schedule Compared to the 2-dose Schedule of Havrix | 289 Participants |
Comparison: Difference in seropositivity rates for anti-HAV antibody: To demonstrate that 1-dose schedule of Havrix (Havrix 1 dose\_Year 10 Group) was non-inferior to the 2-dose schedule of Havrix (Havrix 2 doses\_Year 10 Group), in terms of seropositivity rates for anti-HAV antibody, measured by ELISA, approximately 10 years after the administration of the last vaccine dose.p-value: <0.000195% CI: [-30.11, -19.03]Fisher Exact