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| ID | Type | Description | Link |
|---|---|---|---|
| 100577 (Y12) | Other Identifier | GSK | |
| 100578 (Y13) | Other Identifier | GSK | |
| 100579 (Y14) | Other Identifier | GSK | |
| 100580 (Y15) | Other Identifier | GSK | |
| 111028 (Y16) | Other Identifier | GSK | |
| 111029 (Y17) | Other Identifier | GSK | |
| 111030 (Y18) | Other Identifier | GSK | |
| 111031 (Y19) | Other Identifier | GSK | |
| 111032 (Y20) | Other Identifier | GSK |
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The aim of this study is to evaluate the long-term persistence of hepatitis A antibodies at 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 years after subjects received their first dose of a 2 dose vaccination schedule of hepatitis A vaccine.
This is a long-term follow-up study at Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after primary vaccination with GSK Biologicals' hepatitis A vaccine (two-dose schedule). To evaluate the long-term antibody persistence, volunteers will donate a blood sample at Years 11, 12, 13, 14,15, 16, 17, 18, 19 and 20 after the first vaccine dose of the primary vaccination course to determine their anti-hepatitis A (anti-HAV) antibody concentrations If a subject has become seronegative for anti-HAV antibodies during any of the long-term blood sampling time point (i.e. Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 years), he/ she will be offered an additional vaccine dose. A blood sample will be taken on the day of the additional vaccination, 14 days and one month after additional vaccination to evaluate the immune response following this vaccination.
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007 and to include an extended follow up period up to Year 20 after primary vaccination.
The study has 10 phases (100576, 100577, 100578, 100579, 100580, 111028, 111029, 111030, 111031, 111032).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Havrix Group | Experimental | Subjects who received 2 doses of Havrixâ„¢ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Havrixâ„¢ | Biological | 2 doses at 6 months interval |
|
| Measure | Description | Time Frame |
|---|---|---|
| Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL). The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging. | At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination |
| Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Concentrations given as GMC expressed as mIU/mL. | Before the additional dose, 14 days and 30 days after the additional dose |
| Number of Seropositive Subjects for Anti-HAV Antibodies. | Seropositivity for anti-HAV antibodies defined as antibody concentrations ≥ 15 mIU/mL for Year 11 to Year 20 time points. The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging. | From Year 11 to Year 20 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy | An SAE is any untoward medical occurrence that: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above |
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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 |
|---|---|---|---|
| Background | Desombere I et al. (2000) Long-term persistence of cellular immunity towards hepatitis A vaccine (HAV) following HAV vaccination. J Antiviral Therapy. 5: 7. | ||
| 7897376 | Background | Van Damme P, Mathei C, Thoelen S, Meheus A, Safary A, Andre FE. Single dose inactivated hepatitis A vaccine: rationale and clinical assessment of the safety and immunogenicity. J Med Virol. 1994 Dec;44(4):435-41. doi: 10.1002/jmv.1890440422. | |
| Background | Van Damme P et al. (1998) Long-term immunogenicity of a high potency inactivated hepatitis A vaccine. J Hepatol. 28 (suppl.1): 113. | ||
| Background | Van Herck K et al. (2000) Model-based estimates of long-term persistence of vaccine-induced hepatitis A antibodies. J Antiviral Therapy. 5:3-4. |
| 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 |
|---|---|---|---|
| 100576 (Y11) | Statistical Analysis Plan | 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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The Long-Term (LT) Total Cohort included all subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study.The Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity included subjects who returned for the follow-up and who were included in the ATP cohort for immunogenicity of the primary study.
Participant Flow and Baseline measures are given for the Month 192 (Year 16) time point in order to account for all subjects participating in this long-term follow-up study. Note that not all subjects returned and participated in each of the intermediate follow-up time points.
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| ID | Title | Description |
|---|---|---|
| FG000 | Havrix Group | Subjects who received 2 doses of Havrixâ„¢ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Havrix Group | Subjects who received 2 doses of Havrixâ„¢ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL). The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging. | Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint. | Posted | Geometric Mean | 95% Confidence Interval | mIU/mL | At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination |
|
Until year 20 for SAEs and within 4-days after additional vaccination for other AEs. During the 30-day (Day 0 to Day 29) follow-up period after additional vaccination.
Analyses were performed on the Long-Term (LT) Total Cohort including subjects who returned for the follow-up and who belonged to the Total Cohort in the primary study. For the other AEs only subjects receiving an additional dose were included. Therefore the number of subjects at risk is not consistent with the LT Total Cohort.
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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 | Havrix Group | Subjects who received 2 doses of Havrixâ„¢ (lot A, B or C) in the primary study. As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain | General disorders | Systematic Assessment | Within 4-day period after additional vaccination. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D006506 | Hepatitis A |
| ID | Term |
|---|---|
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D004769 | Enterovirus Infections |
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| ID | Term |
|---|---|
| D022362 | Hepatitis A Vaccines |
| ID | Term |
|---|---|
| D014761 | Viral Hepatitis Vaccines |
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
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| Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain = symptom that prevented normal activities. Grade 3 redness and swelling = redness or swelling above 30 mm and persisting more than 24 hours. Any = incidence of a particular symptom regardless of intensity. | During the 4-day (Day 0-3) follow-up period after additional vaccination |
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed included fatigue, fever, gastrointestinal symptoms, and headache. | During the 4-day (Day 0-3) follow-up period after additional vaccination |
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AE) | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Grade AE = produced significant impairment of functioning or incapacitation and was a definite hazard to the subject's health. Related AE = assessed by the investigator as related to the study vaccination. | During the 30-day follow-up period after additional vaccination (for subjects who received the additional vaccine dose between Year 11 and 15) |
| Number of Subjects Reporting Serious Adverse Events (SAE) | An SAE is any untoward medical occurrence that: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | During the follow-up period after additional vaccination up to Year 20 |
| 11130881 | Background | Van Herck K, Van Damme P. Inactivated hepatitis A vaccine-induced antibodies: follow-up and estimates of long-term persistence. J Med Virol. 2001 Jan;63(1):1-7. |
| 21915861 | Background | Van Herck K, Jacquet JM, Van Damme P. Antibody persistence and immune memory in healthy adults following vaccination with a two-dose inactivated hepatitis A vaccine: long-term follow-up at 15 years. J Med Virol. 2011 Nov;83(11):1885-91. doi: 10.1002/jmv.22200. Epub 2011 Aug 23. |
| 22327499 | Background | Van Herck K, Crasta PD, Messier M, Hardt K, Van Damme P. Seventeen-year antibody persistence in adults primed with two doses of an inactivated hepatitis A vaccine. Hum Vaccin Immunother. 2012 Mar;8(3):323-7. doi: 10.4161/hv.18617. Epub 2012 Feb 13. |
| 32710245 | Derived | Agrawal A, Kolhapure S, Andani A, Ota MOC, Badur S, Karkada N, Mitra M. Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children. Infect Dis Ther. 2020 Dec;9(4):785-796. doi: 10.1007/s40121-020-00311-8. Epub 2020 Jul 24. |
| 26190091 | Derived | Theeten H, Van Herck K, Van Der Meeren O, Crasta P, Van Damme P, Hens N. Long-term antibody persistence after vaccination with a 2-dose Havrix (inactivated hepatitis A vaccine): 20 years of observed data, and long-term model-based predictions. Vaccine. 2015 Oct 13;33(42):5723-5727. doi: 10.1016/j.vaccine.2015.07.008. Epub 2015 Jul 16. |
| 24508042 | Derived | Hens N, Habteab Ghebretinsae A, Hardt K, Van Damme P, Van Herck K. Model based estimates of long-term persistence of inactivated hepatitis A vaccine-induced antibodies in adults. Vaccine. 2014 Mar 14;32(13):1507-13. doi: 10.1016/j.vaccine.2013.10.088. Epub 2014 Feb 7. |
For additional information about this study please refer to the GSK Clinical Study Register |
| 100576 (Y11) | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100576 (Y11) | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100576 (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 100576 are summarised with studies 100577, 100578, 100579, 100580, 111028, 111029, 111030, 111031, and 111032 on the GSK Clinical Study |
| 100576 (Y11) | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 100576 (Y11) | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration | Concentrations given as GMC expressed as mIU/mL. | Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose. | Posted | Number | mIU/mL | Before the additional dose, 14 days and 30 days after the additional dose |
|
|
|
| Primary | Number of Seropositive Subjects for Anti-HAV Antibodies. | Seropositivity for anti-HAV antibodies defined as antibody concentrations ≥ 15 mIU/mL for Year 11 to Year 20 time points. The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging. | Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint. | Posted | Number | Subjects | From Year 11 to Year 20 |
|
|
|
| Secondary | Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy | An SAE is any untoward medical occurrence that: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above | Analysis was performed on the Long Term Total cohort which included all subjects who returned to the follow-up study and who had received at least 1 dose of the vaccine in the primary study. | Posted | Number | Subjects | Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination |
|
|
|
| Secondary | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain = symptom that prevented normal activities. Grade 3 redness and swelling = redness or swelling above 30 mm and persisting more than 24 hours. Any = incidence of a particular symptom regardless of intensity. | Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose. | Posted | Number | Subjects | During the 4-day (Day 0-3) follow-up period after additional vaccination |
|
|
|
| Secondary | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed included fatigue, fever, gastrointestinal symptoms, and headache. | Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose. | Posted | Number | Subjects | During the 4-day (Day 0-3) follow-up period after additional vaccination |
|
|
|
| Secondary | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AE) | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Grade AE = produced significant impairment of functioning or incapacitation and was a definite hazard to the subject's health. Related AE = assessed by the investigator as related to the study vaccination. | Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose. | Posted | Number | Subjects | During the 30-day follow-up period after additional vaccination (for subjects who received the additional vaccine dose between Year 11 and 15) |
|
|
|
| Secondary | Number of Subjects Reporting Serious Adverse Events (SAE) | An SAE is any untoward medical occurrence that: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | Analysis was performed on the Long Term Total cohort, only on subjects who received an additional vaccine dose during the current long-term follow-up study. If a subject became seronegative (< 15 mIU/mL) at any of the long-term blood sampling timepoint, he/she was offered an additional vaccine dose. | Posted | Number | Subjects | During the follow-up period after additional vaccination up to Year 20 |
|
|
|
| 0 |
| 78 |
| 2 |
| 2 |
|
| Influenza like illness | Infections and infestations | Non-systematic Assessment | During the 30-day follow-up period after additional vaccination |
|
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.
| D010850 |
| Picornaviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D045424 |
| Complex Mixtures |
| Title | Measurements |
|---|---|
|
| Subject 2 (pre-additional dose) |
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| Subject 2 (14 days post-additional dose) |
|
| Subject 2 (30 days post-additional dose) |
|
| Title | Measurements |
|---|---|
|
| Year 13 (N=50) |
|
| Year 14 (N=46) |
|
| Year 15 (N=41) |
|
| Year 16 (N=53) |
|
| Year 17 (N=45) |
|
| Year 18 (N=37) |
|
| Year 19 (N=26) |
|
| Year 20 (N=34) |
|
| Title | Measurements |
|---|---|
|
| Year 14 (N=66) |
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| Year 15 (N=63) |
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| Year 16 (N=78) |
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| Year 17 (N=63) |
|
| Year 18 (N=52) |
|
| Year 19 (N=45) |
|
| Year 20 (N=50) |
|
| Title | Measurements |
|---|---|
|
| Grade 3 Pain |
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| Grade 3 Redness > 30 mm |
|
| Grade 3 Swelling > 30 mm |
|
| Title | Measurements |
|---|---|
|
| Any, Grade 3 and Related Headache |
|
| Title | Measurements |
|---|---|
|