Hepatitis APhase 4NCT00684671
Evaluation of Immune Memory to Twinrix or Comparator by Challenge Dose Administration 4 Years After Primary Vaccination
A Phase 4 study testing Twinrix, Engerix-B and Havrix in people with Hepatitis A and Hepatitis B, run by GlaxoSmithKline at 2 sites in 2 countries.
Trial summary
Only subjects who participated in the primary study will be invited to participate in the extension phase and the challenge dose phase of this study. Read more about this study
- Who is it for?
- Ages 41 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hepatitis A, Hepatitis B
- What is being tested?
- Twinrix, Engerix-B and Havrix
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 506 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 26 May 2008to 3 Nov 2008
- 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 41 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
- A male or female who completed the primary vaccination phase of the HAB-160 study (NCT 00603252).
- Written informed consent obtained from the subject.
- If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.
Who cannot join
- The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the challenge dose, or planned use during the study period.
- History of any hepatitis A or hepatitis B vaccination or infection since the primary vaccination study.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
- Acute disease at the time of enrolment.
- Pregnant or lactating female.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Challenge Dose Administration of Twinrix™ or Comparator 4 Years After Primary Vaccination.
Only subjects who participated in the primary study will be invited to participate in the extension phase and the challenge dose phase of this study.
- Conditions
- Hepatitis A, Hepatitis B
- Being tested
- Twinrix, Engerix-B, Havrix, HBVAXPRO, Vaqta
- Keywords
- Immune memory, Combined hepatitis A and B vaccine, > 41 years old
- Medical subject headings
- Hepatitis A, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TwinrixBiological
Intramuscular injection, single dose in left deltoid.
Engerix-BBiological
Intramuscular injection, single dose in left deltoid.
HavrixBiological
Intramuscular injection, single dose in right deltoid.
HBVAXPROBiological
Intramuscular injection, single dose in the left deltoid.
VaqtaBiological
Intramuscular injection, single dose in right deltoid.
| Study group | Role | What they receive |
|---|---|---|
| Twinrix Group | Experimental | Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix). Receives: Biological: Twinrix |
| Engerix + Havrix Group | Active comparator | Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix). Receives: Biological: Engerix-B; Biological: Havrix |
| HB VAX PRO + Vaqta Group | Active comparator | Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta). Receives: Biological: HBVAXPRO; Biological: Vaqta |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies
Anamnestic response was defined as:
- for initially seronegative subjects, antibody concentration greater than or equal the cut-off [≥ 15 Milli-International Units per Milliliter (mIU/mL)],
- for initially seropositive subjects with pre-vaccination antibody, concentration < 100 mIU/mL: antibody concentration at least four times the pre-vaccination antibody concentration,
- for initially seropositive subjects with pre-vaccination antibody concentration ≥ 100 mIU/mL: antibody concentration at least two times the pre-vaccination antibody concentration.
Measured: One month after the challenge dose.
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies
Anamnestic response was defined as :
- for initially seronegative subjects, antibody concentration ≥ 10 Milli-International Units per Milliliter (mIU/mL),
- for initially seropositive subjects: antibody concentration at ≥ 4 fold the pre-vaccination antibody concentration.
Measured: One month after the challenge dose.
Secondary outcomes (6)
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.
Measured: Prior to administration of challenge dose
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.
Measured: Two weeks and one month after the challenge dose
Number of Subjects Reporting Solicited Symptoms
Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache and temperature (above 37 degree Celsius).
Measured: During the 4-day follow-up period after the challenge dose.
Number of Subjects Reporting Unsolicited Symptoms
Unsolicited symptoms = any adverse event (AE) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Measured: During the 31-day follow-up period after the challenge dose.
Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination
A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.
Measured: Since the last study visit of the primary study long-term follow-up study up to challenge dose administration (1 year)
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.
Measured: During one month following the administration of the challenge dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2008 (estimated)
- Study start26 May 2008
- Primary completion3 Nov 2008
- Study completion3 Nov 2008
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 (1)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
- 506 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
- NCT00684671
- Sponsor's protocol ID
- 111572
- Status last verified
- Mar 2017
- First submitted
- 23 May 2008
- 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
Chlibek R, von Sonnenburg F, Van Damme P, Smetana J, Tichy P, Gunapalaiah B, Leyssen M, Jacquet JM. Antibody persistence and immune memory 4 years post-vaccination with combined hepatitis A and B vaccine in adults aged over 40 years. J Travel Med. 2011 Mar-Apr;18(2):145-8. doi: 10.1111/j.1708-8305.2010.00499.x. Epub 2011 Feb 7.
PubMed 21366801
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
- Challenge Dose Administration of Twinrix™ or Comparator 4 Years After Primary Vaccination.
- ClinicalTrials.gov ID
- NCT00684671
- Acronym / sponsor ID
- 111572
- Conditions
- Hepatitis A, Hepatitis B
- Keywords
- Immune memory, Combined hepatitis A and B vaccine, > 41 years old
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 506 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 26 May 2008
- Primary completion
- 3 Nov 2008 (actual)
- Study completion
- 3 Nov 2008 (actual)
- First posted
- 28 May 2008 (estimated)
- Results
- Posted 3 Dec 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Only subjects who participated in the primary study will be invited to participate in the extension phase and the challenge dose phase of this study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Twinrix Group | Experimental | Biological: TwinrixSubjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix). |
| Engerix + Havrix Group | Active comparator | Biological: Engerix-B, Biological: HavrixSubjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix). |
| HB VAX PRO + Vaqta Group | Active comparator | Biological: HBVAXPRO, Biological: VaqtaSubjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta). |
Who may qualify
- Ages
- 41 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
- A male or female who completed the primary vaccination phase of the HAB-160 study (NCT 00603252).
- Written informed consent obtained from the subject.
- If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.
Key exclusion criteria (6 listed)
- The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the challenge dose, or planned use during the study period.
- History of any hepatitis A or hepatitis B vaccination or infection since the primary vaccination study.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
- Acute disease at the time of enrolment.
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 |
|---|---|---|
| TwinrixIntramuscular injection, single dose in left deltoid. | Biological | Twinrix Group |
| Engerix-BIntramuscular injection, single dose in left deltoid. | Biological | Engerix + Havrix Group |
| HavrixIntramuscular injection, single dose in right deltoid. | Biological | Engerix + Havrix Group |
| HBVAXPROIntramuscular injection, single dose in the left deltoid. | Biological | HB VAX PRO + Vaqta Group |
| VaqtaIntramuscular injection, single dose in right deltoid. | Biological | HB VAX PRO + Vaqta Group |
Primary outcome
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies
Time frame: One month after the challenge dose.
Anamnestic response was defined as: * for initially seronegative subjects, antibody concentration greater than or equal the cut-off [≥ 15 Milli-International Units per Milliliter (mIU/mL)], * for initially seropositive subjects with pre-vaccination antibody, concentration < 100 mIU/mL: antibody concentration at least four times the pre-vaccination antibody concentration, * for initially seropositive subjects with pre-vaccination antibody concentration ≥ 100 mIU/mL: antibody concentration at least two times the pre-vaccination antibody concentration.
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies
Time frame: One month after the challenge dose.
Anamnestic response was defined as : * for initially seronegative subjects, antibody concentration ≥ 10 Milli-International Units per Milliliter (mIU/mL), * for initially seropositive subjects: antibody concentration at ≥ 4 fold the pre-vaccination antibody concentration.
6 secondary outcomes
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
Time frame: Prior to administration of challenge dose
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
Time frame: Two weeks and one month after the challenge dose
Number of Subjects Reporting Solicited Symptoms
Time frame: During the 4-day follow-up period after the challenge dose.
Number of Subjects Reporting Unsolicited Symptoms
Time frame: During the 31-day follow-up period after the challenge dose.
Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination
Time frame: Since the last study visit of the primary study long-term follow-up study up to challenge dose administration (1 year)
Number of Subjects Reporting Serious Adverse Events (SAEs)
Time frame: During one month following the administration of the challenge dose
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.
- Derived from this study: PubMed 21366801Chlibek R, von Sonnenburg F, Van Damme P, Smetana J, Tichy P, Gunapalaiah B, Leyssen M, Jacquet JM. Antibody persistence and immune memory 4 years post-vaccination with combined hepatitis A and B vaccine in adults aged over 40 years. J Travel Med. 2011 Mar-Apr;18(2):145-8. doi: 10.1111/j.1708-8305.2010.00499.x. Epub 2011 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
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Twinrix, Engerix-B and Havrix in people with Hepatitis A and Hepatitis B, run by GlaxoSmithKline at 2 sites in 2 countries.
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 4 inclusion and 6 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 2 sites in Belgium, Czechia. 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 3 Dec 2009). 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 Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies (time frame: One month after the challenge dose.). The study lists 2 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 NCT00684671, which also lists 1 linked publication.
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.