Hepatitis APhase 4NCT01000324

Antibody Persistence & Immune Memory in Healthy Adults Previously Vaccinated With Twinrix Adult

A Phase 4 study testing Blood sampling, Engerix-B and Havrix in people with Hepatitis A and Hepatitis B, run by GlaxoSmithKline at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Any ageHealthy volunteers can take part
Conditions the study is for: Hepatitis A, Hepatitis B
What is being tested?: Blood sampling, Engerix-B and Havrix
Type of treatment: Vaccines, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: 1 siteBelgium
Study dates: 6 Nov 2009to 25 Jul 2014
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 Any age
All sexes
Healthy volunteers accepted
Child, Adult, Older adult

Who may be able to join

All subjects must satisfy the following criteria at entry into each of the long-term follow-up visits:
Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
A male or female who received the complete primary vaccination course in the primary study Hepatitis A and B vaccine (HAB), HAB-028 (208127/021).
Written informed consent obtained from the subject.
All subjects must satisfy the following criteria at entry into the challenge dose phase:
Subjects who the investigator believes that they can and will comply with the requirements of the protocol.

Show all 14Show fewer

A male or female who received the complete primary vaccination course in the primary study HAB-028 (208127/021).
Written informed consent obtained from the subject.
Subjects who participated in the long-term follow-up (LTFU) phase of the HAB-028 (208127/021) study and for whom the antibody concentrations were below the cut-off at the last available follow-up time-point.
Female subjects of non-childbearing potential may be enrolled in the study.
Female subjects of childbearing potential may be enrolled in the study, if the subject:
has practiced adequate contraception for 30 days prior to vaccination, and
has a negative pregnancy test on the day of vaccination, and
has agreed to continue adequate contraception for two months after the administration of the challenge dose.

Who cannot join

The following criteria should be checked before entry into each of the long-term follow-up visits. If any exclusion criterion applies, the subject must not be included in the study:
Use of any investigational or non-registered product within 30 days prior to blood sampling.
Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine outside the study procedures, since the primary study HAB-028 (208127/021).
History of hepatitis A or hepatitis B infection since the primary study HAB-028 (208127/021).
Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within three months prior to blood sampling.
The following criteria should be checked before the challenge dose is administered. If any apply, the subject must not be included in the challenge dose phase:

Show all 14Show fewer

Use of any investigational or non-registered product within 30 days prior to study start or planned use during the study.
Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine between the last LTFU visit and the challenge dose visit.
History of hepatitis A or hepatitis B infection between the last LTFU visit and the challenge dose visit.
History of anaphylactic reactions following the administration of vaccines.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
Acute disease and/or fever at the time of enrolment.
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

GSK Investigational Site
Wilrijk, 2610

Other trials in Belgium

About this study

Official title: An Open Single Centre Study to Evaluate the Long-term Antibody Persistence and Immune Memory Between 16 and 20 Years After the Primary Study HAB-028 (208127/021) in Which Healthy Adults Were Vaccinated With Twinrix Adult Following a Three-dose Schedule.

This study will evaluate the persistence of the immune response to HAV (Hepatitis A Virus) antigens and HBs (Hepatitis B surface) antigens in healthy adults previously vaccinated with GlaxoSmithKline (GSK) Biologicals' Twinrix Adult. The subjects will be invited for blood sampling 16, 17, 18, 19 and 20 years after vaccination to evaluate the antibody persistence. For subjects in whom low circulating antibodies are detected, the presence of immune memory against hepatitis A \& B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine (Havrix and/or Engerix-B) at the next planned visit.

No new subjects will be recruited during this study.

Conditions: Hepatitis A, Hepatitis B
Being tested: Blood sampling, Engerix-B, Havrix
Keywords: Hepatitis A, Hepatitis B
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.

Blood samplingProcedure or surgery
Blood sampling at Year 16, 17, 18, 19 and 20 and at the time of challenge dose administration and 14 days and one month after challenge dose administration (if challenge dose needed).
Engerix-BBiological
Engerix-B will be administered to subjects who are not seroprotected against hepatitis B
HavrixBiological
Havrix will be administered to subjects who are seronegative for anti-HAV antibodies

Study groups in NCT01000324
Study group	Role	What they receive
Twinrix Group	Experimental	Pooled group of subjects from groups 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 Receives: Procedure: Blood sampling; Biological: Engerix-B; Biological: Havrix

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL)
Seropositivity for anti-HAV antibodies is defined as antibody concentrations >= 15 milliinternational units per milliliter (mIU/mL). Seropositivity for anti-HBs antibodies is defined as antibody concentrations >= 6.2 mIU/mL.
Measured: At Years 16, 17, 18, 19 and 20.
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)
Concentrations were expressed as GMCs in mIU/mL.
Measured: At Years 16, 17, 18, 19 and 20.

Secondary outcomes (5)

Number of Subjects With Immune Response to the Challenge Vaccine Antigen
None of the subjects received a challenge dose at Years 16, 17, 18 and 20 while, one subject received the challenge dose at Year 19.
Measured: Before, 14 days and one month after the challenge dose at Year 19.
Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration
Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL.
Measured: At Year 18, 14 days and 30 days post challenge dose (Year 19).
Number of Subjects Reporting Unsolicited Adverse Events (AE)
An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Measured: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event was any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Measured: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event is any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, or was a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Measured: 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.

6 Nov 200925 Jul 2014

First posted23 Oct 2009 (estimated)
Study start6 Nov 2009
Primary completion25 Jul 2014
Study completion25 Jul 2014

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01000324
Sponsor's protocol ID: 112267
Status last verified: Jan 2018
First submitted: 22 Oct 2009
Last updated: 4 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No
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

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.
PubMed 32710245

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 4 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Single Centre Study to Evaluate the Long-term Antibody Persistence and Immune Memory Between 16 and 20 Years After the Primary Study HAB-028 (208127/021) in Which Healthy Adults Were Vaccinated With Twinrix Adult Following a Three-dose Schedule.
ClinicalTrials.gov ID: NCT01000324
Acronym / sponsor ID: 112267
Conditions: Hepatitis A, Hepatitis B
Keywords: Hepatitis A, Hepatitis B
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 6 Nov 2009
Primary completion: 25 Jul 2014 (actual)
Study completion: 25 Jul 2014 (actual)
First posted: 23 Oct 2009 (estimated)
Results: Posted 13 Jan 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

No new subjects will be recruited during this study.

Study design

Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Twinrix Group	Experimental	Procedure: Blood sampling, Biological: Engerix-B, Biological: HavrixPooled group of subjects from groups 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

Who may qualify

Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (14 listed)

All subjects must satisfy the following criteria at entry into each of the long-term follow-up visits:
Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
A male or female who received the complete primary vaccination course in the primary study Hepatitis A and B vaccine (HAB), HAB-028 (208127/021).
Written informed consent obtained from the subject.
Subjects who the investigator believes that they can and will comply with the requirements of the protocol.

Key exclusion criteria (14 listed)

The following criteria should be checked before entry into each of the long-term follow-up visits. If any exclusion criterion applies, the subject must not be included in the study:
Use of any investigational or non-registered product within 30 days prior to blood sampling.
Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine outside the study procedures, since the primary study HAB-028 (208127/021).
History of hepatitis A or hepatitis B infection since the primary study HAB-028 (208127/021).
Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within three months prior to blood sampling.

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
Blood samplingBlood sampling at Year 16, 17, 18, 19 and 20 and at the time of challenge dose administration and 14 days and one month after challenge dose administration (if challenge dose needed).	Procedure or surgery	Twinrix Group
Engerix-BEngerix-B will be administered to subjects who are not seroprotected against hepatitis B	Biological	Twinrix Group
HavrixHavrix will be administered to subjects who are seronegative for anti-HAV antibodies	Biological	Twinrix Group

Primary outcome

Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL)
Time frame: At Years 16, 17, 18, 19 and 20.
Seropositivity for anti-HAV antibodies is defined as antibody concentrations >= 15 milliinternational units per milliliter (mIU/mL). Seropositivity for anti-HBs antibodies is defined as antibody concentrations >= 6.2 mIU/mL.
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)
Time frame: At Years 16, 17, 18, 19 and 20.
Concentrations were expressed as GMCs in mIU/mL.

5 secondary outcomes

Number of Subjects With Immune Response to the Challenge Vaccine Antigen
Time frame: Before, 14 days and one month after the challenge dose at Year 19.
Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration
Time frame: At Year 18, 14 days and 30 days post challenge dose (Year 19).
Number of Subjects Reporting Unsolicited Adverse Events (AE)
Time frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.
Number of Subjects Reporting Serious Adverse Events (SAEs)
Time frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19.
Number of Subjects Reporting Serious Adverse Events (SAEs)
Time frame: Up to Year 20.

Results and safety

Results posted to the registry on 13 Jan 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Twinrix Group	40	40

Primary outcome: Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL)

Time frame: At Years 16, 17, 18, 19 and 20.. Number. Unit: Subjects

Measure	Twinrix Group n = 23
Anti-HAV >=15 mIU/mL [at Year 16] (N=23)	23
anti-HBs >= 6.2 mIU/mL [at Year 16] (N=23)	20
anti-HBs >= 10 mIU/mL [at Year 16] (N=23)	20
anti-HAV >= 15 mIU/mL [at Year 17] (N=19)	19
anti-HBs >= 6.2 mIU/mL [at Year 17] (N=19)	17
anti-HBs >= 10 mIU/mL [at Year 17] (N=19)	17
anti-HAV >= 15 mIU/mL [at Year 18] (N=10)	10
anti-HBs >= 6.2 mIU/mL [at Year 18] (N=10)	9

Population analysed: The analysis was performed on the Long-Term (LT) According-to-Protocol (ATP) cohort for analysis of immunogenicity. They were included in the ATP analysis for the primary study, did not receive hepatitis A or B (hep A/B) vaccination that was not specified in the protocol and were not eliminated for abnormal increase of antibody concentrations.

Primary outcome: Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)

Time frame: At Years 16, 17, 18, 19 and 20.. Geometric mean (95% Confidence Interval). Unit: milli-international units per milliliter

Measure	Twinrix Group n = 23
anti-HAV [at Year 16] (N=23)	614.2 (404.1 to 933.6)
anti-HBs [at Year 16] (N=23)	138.7 (61.3 to 313.7)
anti-HAV [at Year 17] (N=19)	479.2 (298.2 to 769.9)
anti-HBs [at Year 17] (N=19)	165.1 (64.8 to 420.7)
anti-HAV [at Year 18] (N=10)	653.2 (333.2 to 1280.6)
anti-HBs [at Year 18] (N=10)	278.3 (70.3 to 1101.3)
anti-HAV [at Year 19] (N=17)	728.7 (469.6 to 1130.5)
anti-HBs [at Year 19] (N=18)	198.4 (80.1 to 491.3)

Population analysed: The analysis was performed on the Long-Term (LT) According-to-Protocol (ATP) cohort for analysis of immunogenicity.They were included in the ATP analysis for the primary study, did not receive hepatitis A or B vaccination that was not specified in the protocol and were not eliminated for abnormal increase of antibody concentrations.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: SAEs: During the 31-day (Days 0 to 30) follow-up period after the challenge dose and from the beginning of the long term follow-up to Year 20; Unsolicited symptoms: During the 31-day (Days 0 to 30) follow-up period after the challenge dose.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Twinrix Group	0 of 40 (0%)	1 of 1 (100%)	0 of 40

Limitations and caveats (from the sponsor): 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 partial or complete retesting/reanalysis.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
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 Blood sampling, Engerix-B and Havrix in people with Hepatitis A and Hepatitis B, 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 14 inclusion and 14 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 4 Sep 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 13 Jan 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 Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL) (time frame: At Years 16, 17, 18, 19 and 20.). 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 NCT01000324, 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 4 Sep 2018.