Hepatitis APhase 4NCT00289757
Long-Term Immune Persistence of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine, Injected According to 0, 6-month Schedule
A Phase 4 study testing Havrix™ in people with Hepatitis A, run by GlaxoSmithKline at 1 site in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 29 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis A
- What is being tested?
- Havrix™
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Jan 2004to 1 Mar 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 29 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects who had received at least one dose of the study vaccine in the primary study
- Written informed consent will have been obtained from the subjects before the blood sampling visit of each year.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double-blind, Randomized Study to Evaluate the Immunogenicity and Reactogenicity of Three Different Lots of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Containing 1440 EL.U of Antigen Per mL and Injected According to a 0, 6 Month Schedule in Healthy Adult Subjects
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.
Read the detailed description
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).
- Conditions
- Hepatitis A
- Being tested
- Havrix™
- Keywords
- Havrix™, Hepatitis A
- Medical subject headings
- Hepatitis A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Havrix™Biological
2 doses at 6 months interval
| Study group | Role | What they receive |
|---|---|---|
| Havrix Group | Experimental | Subjects who received 2 doses of Havrix™ (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. Receives: Biological: Havrix™ |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: From Year 11 to Year 20
Secondary outcomes (5)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: During the follow-up period after additional vaccination up to Year 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2006 (estimated)
- Study start1 Jan 2004
- Primary completion1 Mar 2013
- Study completion1 Mar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Hepatitis AStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00289757
- Sponsor's protocol ID
- 100576 (Y11)
- Other IDs
- 100577 (Y12), 100578 (Y13), 100579 (Y14), 100580 (Y15), 111028 (Y16), 111029 (Y17), 111030 (Y18), 111031 (Y19)
- Status last verified
- Sep 2016
- First submitted
- 9 Feb 2006
- Last updated
- 23 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Desombere I et al. (2000) Long-term persistence of cellular immunity towards hepatitis A vaccine (HAV) following HAV vaccination. J Antiviral Therapy. 5: 7.
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.
PubMed 7897376Van Damme P et al. (1998) Long-term immunogenicity of a high potency inactivated hepatitis A vaccine. J Hepatol. 28 (suppl.1): 113.
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.
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.
PubMed 11130881Van 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.
PubMed 21915861Van 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.
PubMed 22327499Agrawal 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.
PubMed 32710245Theeten 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.
PubMed 26190091Hens 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.
PubMed 24508042
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-blind, Randomized Study to Evaluate the Immunogenicity and Reactogenicity of Three Different Lots of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Containing 1440 EL.U of Antigen Per mL and Injected According to a 0, 6 Month Schedule in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT00289757
- Acronym / sponsor ID
- 100576 (Y11)
- Conditions
- Hepatitis A
- Keywords
- Havrix™, Hepatitis A
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Jan 2004
- Primary completion
- 1 Mar 2013 (actual)
- Study completion
- 1 Mar 2013 (actual)
- First posted
- 10 Feb 2006 (estimated)
- Results
- Posted 4 Mar 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Havrix Group | Experimental | Biological: Havrix™Subjects who received 2 doses of Havrix™ (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. |
Who may qualify
- Ages
- 29 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Subjects who had received at least one dose of the study vaccine in the primary study
- Written informed consent will have been obtained from the subjects before the blood sampling visit of each year.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Havrix™2 doses at 6 months interval | Biological | Havrix Group |
Primary outcome
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration
Time frame: At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination
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.
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration
Time frame: Before the additional dose, 14 days and 30 days after the additional dose
Concentrations given as GMC expressed as mIU/mL.
Number of Seropositive Subjects for Anti-HAV Antibodies.
Time frame: From Year 11 to Year 20
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.
5 secondary outcomes
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: During the follow-up period after additional vaccination up to Year 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundDesombere I et al. (2000) Long-term persistence of cellular immunity towards hepatitis A vaccine (HAV) following HAV vaccination. J Antiviral Therapy. 5: 7.
- Background: PubMed 7897376Van 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.
- BackgroundVan Damme P et al. (1998) Long-term immunogenicity of a high potency inactivated hepatitis A vaccine. J Hepatol. 28 (suppl.1): 113.
- BackgroundVan Herck K et al. (2000) Model-based estimates of long-term persistence of vaccine-induced hepatitis A antibodies. J Antiviral Therapy. 5:3-4.
- Background: PubMed 11130881Van 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.
- Background: PubMed 21915861Van 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.
- Background: PubMed 22327499Van 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.
- Derived from this study: PubMed 32710245Agrawal 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.
- Derived from this study: PubMed 26190091Theeten 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.
- Derived from this study: PubMed 24508042Hens 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.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Havrix™ in people with Hepatitis A, run by GlaxoSmithKline at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration (time frame: At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00289757, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2018.