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| ID | Type | Description | Link |
|---|---|---|---|
| 100552 (EXT Y12) | Other Identifier | GSK | |
| 100553 (EXT Y13) | Other Identifier | GSK | |
| 100554 (EXT Y14) | Other Identifier | GSK | |
| 100555 (EXT Y15) | Other Identifier | GSK |
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The aim of this study is to evaluate the long-term persistence of hepatitis A and B antibodies at Years 11, 12, 13, 14 and 15 after subjects received their first dose of a 3 dose primary vaccination schedule of combined hepatitis A/hepatitis B vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
This protocol posting deals with objectives & outcome measures of the extension phase at Year 11-15.
This is a long-term follow-up study at Years 11, 12, 13, 14 and 15 after primary vaccination with GSK Biologicals' hepatitis A/hepatitis B vaccine (three-dose schedule with 3 different lots). To evaluate the long-term antibody persistence, volunteers will be bled at Years 11, 12, 13, 14 and 15 after the first vaccine dose of the primary vaccination course to determine their anti-HAV and anti-HBs antibody concentrations.
No additional subjects will be recruited in the course of this extension study. 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 11, 12, 13, 14 or 15), he/ she will be offered an additional vaccine dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | Was vaccinated with Lot A in the primary study. |
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| Group B | Experimental | Was vaccinated with Lot B in the primary study. |
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| Group C | Experimental | Was vaccinated with Lot C in the primary study. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Twinrixâ„¢ | Biological | Intramuscular injection, 3 doses |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value | Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity. | Years 11, 12, 13, 14 and 15 |
| Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Cut-off values were defined 3.3 mIU/mL for the in-house anti-HBs assay and 6.2 mIU/mL for the ChemiLuminescence ImmunoAssay, which was also considered as seropositivity, and 10 mIU/mL. | Years 11, 12, 13, 14 and 15 |
| Anti-HAV and Anti-HBs Antibody Concentrations | Concentrations are expressed as geometric mean concentrations (GMCs) in mIU/mL. The laboratory assay was changed from Year 13 to Year 14 to in-house ELISA and at Year 15 to CLIA for anti-HBs GMCs.Thus for the sake of bridging, blood samples corresponding to Year 14 previously tested with ELISA were re-tested with CLIA (Year 14*). | Years 11, 12, 13, 14 and 15 |
| Anti-HBs Antibody Concentrations | Subjects who lost seroprotective concentrations for anti-HBs (< 10 mIU/mL) at any of the LT follow-up timepoints received an additional dose of Engerix after year 15. Two subjects were eligible for this after Year 11. 3.29 in the table means a concentration of < 3.3 mIU/mL. As the concentration was calculated per subject no mean concentration was calculated and also no measure of dispersion. | at Year 11, pre-additional vaccine, after additional dose of Engerix |
| Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response | Anamnestic response was assessed in subjects receiving an additional vaccine dose of Engerix. Two subjects were found eligible at Year 11 for this additional vaccine dose. Anamnestic response was defined as:
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Wilrijk | 2610 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22052690 | Background | Van Damme P, Leroux-Roels G, Crasta P, Messier M, Jacquet JM, Van Herck K. Antibody persistence and immune memory in adults, 15 years after a three-dose schedule of a combined hepatitis A and B vaccine. J Med Virol. 2012 Jan;84(1):11-7. doi: 10.1002/jmv.22264. Epub 2011 Nov 3. | |
| 11505437 | Background | Van Damme P, Leroux-Roels G, Law B, Diaz-Mitoma F, Desombere I, Collard F, Tornieporth N, Van Herck K. Long-term persistence of antibodies induced by vaccination and safety follow-up, with the first combined vaccine against hepatitis A and B in children and adults. J Med Virol. 2001 Sep;65(1):6-13. |
| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 100551 (EXT Y11) | Clinical Study Report | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Subjects who came back at a follow-up, did not necessarily come back at an earlier timepoint. Therefore amount of subjects who completed the previous timepoint does not always correspond with amount of subjects who entered follow-up. As Year 15 has enrolled the most subjects, baseline measures are given for Year 15, to be as complete as possible.
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| ID | Title | Description |
|---|---|---|
| FG000 | Twinrix Group | Subjects 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Year 11 |
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| Year 12 |
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| Year 13 |
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| Year 14 |
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| Year 15 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Twinrix Group | Subjects 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 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value | Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity. | Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint. | Posted | Count of Participants | Participants | Years 11, 12, 13, 14 and 15 |
|
SAEs were collected up to Year 15. Other adverse events were collected within 4-days after additional vaccination (solicited) and 30-days after additional vaccination (unsolicited).
As the number of subjects differs for SAEs at the different timepoints the maximum number has been taken for the amount of subjects at risk.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Twinrix Group | Subjects 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | Systematic Assessment |
A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D006506 | Hepatitis A |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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| ID | Term |
|---|---|
| C433226 | twinrix |
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| 30 days post additional dose of Engerix |
| Number of Subjects With Solicited Local and General Symptoms Assessed | Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache. | During the 4-day follow-up period after additional vaccination with Engerix |
| Number of Subjects With Unsolicited Symptoms | Unsolicited 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. | During the 30-day follow-up period after additional Engerix vaccination |
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are 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 | During the 30-day follow-up period after additional Engerix vaccination |
| Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy | SAEs assessed include medical occurrences that result in death, are 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. | up to Year 11, 12, 13, 14, 15 |
| 17448944 | Background | Van Herck K, Leroux-Roels G, Van Damme P, Srinivasa K, Hoet B. Ten-year antibody persistence induced by hepatitis A and B vaccine (Twinrix) in adults. Travel Med Infect Dis. 2007 May;5(3):171-5. doi: 10.1016/j.tmaid.2006.07.003. Epub 2006 Sep 20. |
For additional information about this study please refer to the GSK Clinical Study Register |
| 100551 (EXT Y11) | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 100551 are summarised with studies 100552, 100553, 100554, and 100555 on the GSK Clinical Study Register. |
| 100551 (EXT Y11) | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100551 (EXT Y11) | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100551 (EXT Y11) | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values | Cut-off values were defined 3.3 mIU/mL for the in-house anti-HBs assay and 6.2 mIU/mL for the ChemiLuminescence ImmunoAssay, which was also considered as seropositivity, and 10 mIU/mL. | Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint. | Posted | Count of Participants | Participants | Years 11, 12, 13, 14 and 15 |
|
|
|
| Primary | Anti-HAV and Anti-HBs Antibody Concentrations | Concentrations are expressed as geometric mean concentrations (GMCs) in mIU/mL. The laboratory assay was changed from Year 13 to Year 14 to in-house ELISA and at Year 15 to CLIA for anti-HBs GMCs.Thus for the sake of bridging, blood samples corresponding to Year 14 previously tested with ELISA were re-tested with CLIA (Year 14*). | Analysis was performed on the long-term (LT) According-To-Protocol (ATP) cohort for immunogenicity, which included subjects who returned at a particular blood sampling timepoint, were in the ATP immunogenicity cohort in the primary study and for whom serology results were available for that particular timepoint. | Posted | Geometric Mean | 95% Confidence Interval | mIU/mL | Years 11, 12, 13, 14 and 15 |
|
|
|
| Primary | Anti-HBs Antibody Concentrations | Subjects who lost seroprotective concentrations for anti-HBs (< 10 mIU/mL) at any of the LT follow-up timepoints received an additional dose of Engerix after year 15. Two subjects were eligible for this after Year 11. 3.29 in the table means a concentration of < 3.3 mIU/mL. As the concentration was calculated per subject no mean concentration was calculated and also no measure of dispersion. | Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available. | Posted | Number | mIU/mL | at Year 11, pre-additional vaccine, after additional dose of Engerix |
|
|
|
| Primary | Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response | Anamnestic response was assessed in subjects receiving an additional vaccine dose of Engerix. Two subjects were found eligible at Year 11 for this additional vaccine dose. Anamnestic response was defined as:
| Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available. | Posted | Count of Participants | Participants | 30 days post additional dose of Engerix |
|
|
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| Primary | Number of Subjects With Solicited Local and General Symptoms Assessed | Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache. | Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available. | Posted | Count of Participants | Participants | During the 4-day follow-up period after additional vaccination with Engerix |
|
|
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| Primary | Number of Subjects With Unsolicited Symptoms | Unsolicited 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. | Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available. | Posted | Count of Participants | Participants | During the 30-day follow-up period after additional Engerix vaccination |
|
|
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| Primary | Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are 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 | Analysis was performed on the long-term (LT) Total Vaccinated Cohort in subjects who were eligible for an additional dose. This included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling timepoint and who had serology results for anti-HAV and anti-HBs available. | Posted | Count of Participants | Participants | During the 30-day follow-up period after additional Engerix vaccination |
|
|
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| Primary | Number of Subjects With Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy | SAEs assessed include medical occurrences that result in death, are 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. | Analysis was performed on the long-term (LT) Total Vaccinated Cohort, this included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the blood sampling time-point and who had serology results for anti-HAV and anti-HBs available. | Posted | Count of Participants | Participants | up to Year 11, 12, 13, 14, 15 |
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| 0 |
| 50 |
| 2 |
| 2 |
| Gastrointestinal | General disorders | Systematic Assessment |
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| Heaviness sensation above eyes | Eye disorders | Non-systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D004769 | Enterovirus Infections |
| D010850 | Picornaviridae Infections |
| D012327 | RNA Virus Infections |
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| Year 13 3.3 mIU/mL |
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| Year 14 3.3 mIU/mL |
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| Year 14 6.2 mIU/mL |
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| Year 15 6.2 mIU/mL |
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| Year 11 10 mIU/mL |
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| Year 12 10 mIU/mL |
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| Year 13 10 mIU/mL |
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| Year 14 10 mIU/mL |
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| Year 15 10 mIU/mL |
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| Year 13 anti-HAV |
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| Year 14 anti-HAV |
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| Year 15 anti-HAV |
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| Year 11 anti-HBs |
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| Year 12 anti-HBs |
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| Year 13 anti-HBs |
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| Year 14 anti-HBs |
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| Year 14* anti-HBs |
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| Year 15 anti-HBs |
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| Title | Measurements |
|---|---|
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| subject 2 before additional dose |
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| subject 1 after additional dose |
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| subject 2 after additional dose |
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| Title | Measurements |
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| Fatigue |
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| Fever |
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| Gastrointestinal |
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| Headache |
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| Year 13 |
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| Year 14 |
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| Year 15 |
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