Hepatitis BPhase 3NCT00289770
Long-term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Mth Schedule in Healthy Adults
A Phase 3 study testing Twinrix™ in people with Hepatitis B and 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 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B, Hepatitis A
- What is being tested?
- Twinrix™
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Nov 2004to 20 Dec 2004
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects who had consented to participate in the long-term follow-up studies at the previous long-term blood sampling time points
- Written informed consent will have been obtained from each subject. 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: A Double Blind Randomised, Comparative Study of the Immunogenicity and Reactogenicity of Three Different Lots of GlaxoSmithKline Biologicals' Combined Hepatitis A - Hepatitis B Vaccine When Administered in Healthy Adults
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.
Read the detailed description
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.
- Conditions
- Hepatitis B, Hepatitis A
- Being tested
- Twinrix™
- Keywords
- TWINRIX™ ADULT, Hepatitis A, Hepatitis B
- Medical subject headings
- Hepatitis B, Hepatitis A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Twinrix™Biological
Intramuscular injection, 3 doses
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Was vaccinated with Lot A in the primary study. Receives: Biological: Twinrix™ |
| Group B | Experimental | Was vaccinated with Lot B in the primary study. Receives: Biological: Twinrix™ |
| Group C | Experimental | Was vaccinated with Lot C in the primary study. Receives: Biological: Twinrix™ |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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*).
Measured: 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.
Measured: 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:
- post-additional vaccination anti-HBs concentration >= 10 mIU/mL in subject seronegative before additional dose.
- 4-fold increase post-additional dose compared to pre-additional vaccine time point.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: up to Year 11, 12, 13, 14, 15
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 Nov 2004
- Primary completion20 Dec 2004
- Study completion20 Dec 2004
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 (3)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 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
- NCT00289770
- Sponsor's protocol ID
- 100551 (EXT Y11)
- Other IDs
- 100552 (EXT Y12), 100553 (EXT Y13), 100554 (EXT Y14), 100555 (EXT Y15)
- Status last verified
- Sep 2016
- First submitted
- 9 Feb 2006
- Last updated
- 17 Aug 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
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.
PubMed 22052690Van 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.
PubMed 11505437Van 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.
PubMed 17448944
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Randomised, Comparative Study of the Immunogenicity and Reactogenicity of Three Different Lots of GlaxoSmithKline Biologicals' Combined Hepatitis A - Hepatitis B Vaccine When Administered in Healthy Adults
- ClinicalTrials.gov ID
- NCT00289770
- Acronym / sponsor ID
- 100551 (EXT Y11)
- Conditions
- Hepatitis B, Hepatitis A
- Keywords
- TWINRIX™ ADULT, Hepatitis A, Hepatitis B
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2004
- Primary completion
- 20 Dec 2004 (actual)
- Study completion
- 20 Dec 2004 (actual)
- First posted
- 10 Feb 2006 (estimated)
- Results
- Posted 23 Feb 2011
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 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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Biological: Twinrix™Was vaccinated with Lot A in the primary study. |
| Group B | Experimental | Biological: Twinrix™Was vaccinated with Lot B in the primary study. |
| Group C | Experimental | Biological: Twinrix™Was vaccinated with Lot C in the primary study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects who had consented to participate in the long-term follow-up studies at the previous long-term blood sampling time points
- Written informed consent will have been obtained from each subject. 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 |
|---|---|---|
| Twinrix™Intramuscular injection, 3 doses | Biological | Group A, Group B, Group C |
Primary outcome
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value
Time frame: Years 11, 12, 13, 14 and 15
Cut-off value was defined as 15 milli-international units per milliliter (mIU/mL). This was considered as seropositivity.
Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values
Time frame: Years 11, 12, 13, 14 and 15
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.
Anti-HAV and Anti-HBs Antibody Concentrations
Time frame: Years 11, 12, 13, 14 and 15
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*).
Anti-HBs Antibody Concentrations
Time frame: at Year 11, pre-additional vaccine, after additional dose of Engerix
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.
Number of Subjects, Receiving an Additional Vaccination of Engerix, With an Anamnestic Response
Time frame: 30 days post additional dose of Engerix
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: * post-additional vaccination anti-HBs concentration >= 10 mIU/mL in subject seronegative before additional dose. * 4-fold increase post-additional dose compared to pre-additional vaccine time point.
Number of Subjects With Solicited Local and General Symptoms Assessed
Time frame: During the 4-day follow-up period after additional vaccination with Engerix
Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were fatigue, fever, gastrointestinal, headache.
Number of Subjects With Unsolicited Symptoms
Time frame: During the 30-day follow-up period after additional Engerix vaccination
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.
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: During the 30-day follow-up period after additional Engerix vaccination
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
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
Time frame: up to Year 11, 12, 13, 14, 15
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22052690Van 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.
- Background: PubMed 11505437Van 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.
- Background: PubMed 17448944Van 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.
- 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 3 study testing Twinrix™ in people with Hepatitis B and 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 17 Aug 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 23 Feb 2011). 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?
Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentrations Equal to or Above Cut-off Value (time frame: Years 11, 12, 13, 14 and 15). The study lists 9 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 NCT00289770, which also lists 3 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 17 Aug 2018.