Hepatitis BPhase 4NCT00875485

Evaluation of Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™

A Phase 4 study testing Blood sampling and Additional challenge dose in people with Hepatitis B and Hepatitis A, run by GlaxoSmithKline at 2 sites in 2 countries.

Completed

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

Official record

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Trial summary

Who is it for?: Ages 12 to 15 yearsHealthy volunteers can take part
Conditions the study is for: Hepatitis B, Hepatitis A
What is being tested?: Blood sampling and Additional challenge dose
Type of treatment: Vaccines, Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 210 participants
Where: 2 sitesin 2 countries
Study dates: 1 May 2009to 1 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 12 to 15 years
All sexes
Healthy volunteers accepted
Child

Who may be able to join

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 according to his/her group allocation in the primary study
Written informed consent obtained from the subject.
All subjects must satisfy the following criteria at entry into the challenge dose phase:
A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study.
Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points.

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Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
Written informed consent obtained from the subject.
Healthy subjects as established by medical history and clinical examination before entering into the challenge dose phase of this study.
If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized; 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 each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit.
Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit.
Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study.
History of hepatitis A or hepatitis B infection.
Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 months prior to blood sampling.
The following criteria should be checked before the challenge dose phase. If any apply, the subject must not be included in the challenge dose phase:

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Use of any investigational or non-registered product (drug or vaccine) within 30 days before the administration of the challenge dose or planned use during the study period outside the context of the study.
Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine between the primary vaccination course of the primary study and the challenge dose visit.
History of hepatitis A or hepatitis B infection.
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
Acute disease at the time of.
Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the challenge dose or planned administration before the final blood sampling point (one month after the challenge dose).
Pregnant or lactating female.

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

Belgium1 site

GSK Investigational Site
Brussels, 1200

Other trials in Belgium

Czechia1 site

GSK Investigational Site
Hradec Králové, 500 03

Other trials in Czechia

About this study

Official title: An Open Multicentre, Multicountry Study to Evaluate Long-term Antibody Persistence and Immune Memory Between Years 11 and 15 After the Primary Study HAB-084 in Which Healthy Adolescents Were Vaccinated With Twinrix™ Adult Following a Two-dose Schedule or Twinrix™ Junior Following a Three-dose Schedule.

This study will evaluate the immune response against Hepatitis-A (HAV) and Hepatitis B surface (HBs) antigen in healthy subjects aged 12 to 15 years (at the time of primary vaccination), who received vaccination course with GSK Biologicals' Twinrix Adult and Twinrix Junior vaccine, approximately 10 years ago in the primary study. The subjects will be invited for blood sampling at 11, 12, 13, 14 and 15 years after primary vaccination to evaluate the persistence of immune response. For subjects detected with decreased immunity, the presence of immune memory against hepatitis A \& B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine 6 to 12 months after the Year 15 follow-up time-point.

No new subjects will be recruited during this booster phase of the study.

Conditions: Hepatitis B, Hepatitis A
Being tested: Blood sampling, Additional challenge dose
Keywords: Monovalent Hepatitis A, hepatitis B vaccine, Belgium and Czech Republic
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.

Blood samplingProcedure or surgery
Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
Additional challenge doseBiological
If a subject became seronegative for anti-HAV antibodies (< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.

Study groups in NCT00875485
Study group	Role	What they receive
Twinrix Adult Group	Experimental	Subjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study Receives: Procedure: Blood sampling; Biological: Additional challenge dose
Twinrix Junior Group	Experimental	Subjects received 3 doses of Twinrix™ Junior (= half dose Twinrix™ Adult) intramuscularly according to a 0, 1, 6 month schedule in the primary study Receives: Procedure: Blood sampling; Biological: Additional challenge dose

What is being measured

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

Anti-HAV Antibody Concentrations
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.
Measured: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084
Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values
Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL. Note: 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 complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA).
Measured: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084
Anti-HBs Antibody Concentrations
Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL.
Note: 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 complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA.
Measured: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.
Anti-HBs Anamnestic Response.
Anamnestic response was defined as:
Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points.
At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points.
Measured: One month after the challenge dose.
Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value.
Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL).
Measured: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.

Secondary outcomes (13)

Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 11.
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 12.
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 13.
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 14.
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
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: Since the last long-term follow-up visit up to Year 15.
Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value.
Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL).
Note: Since none of the subjects were seronegative for anti-HAV antibody concentration at the pre-challenge time point, subjects received only the HBV vaccine as the challenge dose.
Measured: Before (PRE) the challenge dose
Anti-HAV Antibody Concentrations
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.
Measured: Before (PRE) the challenge dose
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events.
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
Measured: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose
Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values
Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL
Measured: Before (PRE) and one month after (POST) the challenge dose
Anti-HBs Antibody Concentrations
Antibody concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL.
Measured: Before (PRE) and one month after (POST) the challenge dose
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever (axillary temperature). Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature > 39.5°C. Related = general symptoms which were assessed by the investigator as causally related to vaccination.
Measured: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose.
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms.
An unsolicited AE covers 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. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. Grade 3 = AE that prevented normal activity. Related = AE assessed by the investigator as causally related to the study vaccination.
Measured: During the 31-day (Day 0 to 30) follow-up period after the challenge dose.
Number of Subjects With Serious Adverse Events (SAEs).
Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were 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.
Measured: One month after the administration of the challenge dose (Month 0 to Month 1)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 May 20091 Jul 2014

First posted3 Apr 2009 (estimated)
Study start1 May 2009
Primary completion1 Jul 2014
Study completion1 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 (2)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 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 210 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00875485
Sponsor's protocol ID: 110699
Other IDs: 110700, 110701, 110702, 110703, 110704
Status last verified: Jul 2018
First submitted: 2 Apr 2009
Last updated: 20 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

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
Beran J, Van Der Meeren O, Leyssen M, D'silva P. Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine. Vaccine. 2016 May 23;34(24):2686-91. doi: 10.1016/j.vaccine.2016.04.033. Epub 2016 Apr 20.
PubMed 27105563

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?

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Study at a glance

From the registry record, last updated by the sponsor on 20 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Multicentre, Multicountry Study to Evaluate Long-term Antibody Persistence and Immune Memory Between Years 11 and 15 After the Primary Study HAB-084 in Which Healthy Adolescents Were Vaccinated With Twinrix™ Adult Following a Two-dose Schedule or Twinrix™ Junior Following a Three-dose Schedule.
ClinicalTrials.gov ID: NCT00875485
Acronym / sponsor ID: 110699
Conditions: Hepatitis B, Hepatitis A
Keywords: Monovalent Hepatitis A, hepatitis B vaccine, Belgium and Czech Republic
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 210 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 1 May 2009
Primary completion: 1 Jul 2014 (actual)
Study completion: 1 Jul 2014 (actual)
First posted: 3 Apr 2009 (estimated)
Results: Posted 5 Jul 2010

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 booster phase of the study.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Twinrix Adult Group	Experimental	Procedure: Blood sampling, Biological: Additional challenge doseSubjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study
Twinrix Junior Group	Experimental	Procedure: Blood sampling, Biological: Additional challenge doseSubjects received 3 doses of Twinrix™ Junior (= half dose Twinrix™ Adult) intramuscularly according to a 0, 1, 6 month schedule in the primary study

Who may qualify

Ages: 12 to 15 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (10 listed)

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 according to his/her group allocation in the primary study
Written informed consent obtained from the subject.
A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study.
Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points.

Key exclusion criteria (15 listed)

The following criteria should be checked at each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit.
Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit.
Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study.
History of hepatitis A or hepatitis B infection.
Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 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 Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.	Procedure or surgery	Twinrix Adult Group, Twinrix Junior Group
Additional challenge doseIf a subject became seronegative for anti-HAV antibodies (< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.	Biological	Twinrix Adult Group, Twinrix Junior Group

Primary outcome

Anti-HAV Antibody Concentrations
Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.
Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values
Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084
Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL. Note: 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 complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA).
Anti-HBs Antibody Concentrations
Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.
Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL. Note: 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 complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA.
Anti-HBs Anamnestic Response.
Time frame: One month after the challenge dose.
Anamnestic response was defined as: Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points. At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points.
Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value.
Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.
Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL).

13 secondary outcomes

Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Time frame: Since the last long-term follow-up visit up to Year 11.
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Time frame: Since the last long-term follow-up visit up to Year 12.
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Time frame: Since the last long-term follow-up visit up to Year 13.
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Time frame: Since the last long-term follow-up visit up to Year 14.
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
Time frame: Since the last long-term follow-up visit up to Year 15.
Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value.
Time frame: Before (PRE) the challenge dose
Anti-HAV Antibody Concentrations
Time frame: Before (PRE) the challenge dose
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events.
Time frame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose
Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values
Time frame: Before (PRE) and one month after (POST) the challenge dose
Anti-HBs Antibody Concentrations
Time frame: Before (PRE) and one month after (POST) the challenge dose
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
Time frame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose.
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms.
Time frame: During the 31-day (Day 0 to 30) follow-up period after the challenge dose.
Number of Subjects With Serious Adverse Events (SAEs).
Time frame: One month after the administration of the challenge dose (Month 0 to Month 1)

Results and safety

Results posted to the registry on 5 Jul 2010, 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 Adult Group	99	99
Twinrix Junior Group	111	111

Primary outcome: Anti-HAV Antibody Concentrations

Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084. Geometric mean (95% Confidence Interval). Unit: mIU/mL

Measure	Twinrix Adult Group n = 78	Twinrix Junior Group n = 92
Year 11 (N= 78; 92)	360.5 (292.0 to 445.1)	257.2 (215.1 to 307.5)
Year 12 (N= 75; 90)	450.8 (359.6 to 565.1)	335.6 (279.0 to 403.6)
Year 13 (N= 77; 92)	401.5 (328.2 to 491.1)	293.6 (244.2 to 352.9)
Year 14 (N= 75; 91)	388.0 (309.2 to 487.0)	291.4 (240.6 to 352.9)
Year 15 (N= 74; 88)	387.5 (306.6 to 489.8)	299.4 (247.6 to 362.0)

Population analysed: Analysis was performed on subjects from the Long Term According-to-Protocol (LT ATP) cohort for immunogenicity on anti-HAV seropositive subjects with available data at the specified time-points.

Primary outcome: Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values

Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084. Number. Unit: Subjects

Measure	Twinrix Adult Group n = 78	Twinrix Junior Group n = 92
Year 11 [6.2 mIU/mL] (N = 78;91)	68	79
Year 12 [6.2 mIU/mL] (N = 75;90)	64	80
Year 13 [6.2 mIU/mL] (N = 77;92)	65	83
Year 14 [6.2 mIU/mL] (N= 75;91)	66	80
Year 15 [6.2 mIU/mL] (N= 74;88)	62	79
Year 11 [10 mIU/mL] (N = 78;91)	64	75
Year 12 [10 mIU/mL] (N = 75;90)	62	76
Year 13 [10 mIU/mL] (N = 77;92)	62	77

Population analysed: Analysis was performed on subjects from the Long Term According-to-Protocol (LT ATP) cohort for immunogenicity on subjects with available data at the specified time-points

Primary outcome: Anti-HBs Antibody Concentrations

Time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.. Geometric mean (95% Confidence Interval). Unit: mIU/mL

Measure	Twinrix Adult Group n = 78	Twinrix Junior Group n = 92
Year 11 (N = 78;91)	88.0 (63.2 to 122.5)	75.2 (55.6 to 101.8)
Year 12 (N = 75;90)	93.3 (66.2 to 131.6)	77.0 (56.1 to 105.7)
Year 13 (N = 77;92)	92.4 (65.9 to 129.5)	70.1 (51.2 to 96.0)
Year 14 (N= 75;91)	81.8 (57.5 to 116.4)	70.2 (51.0 to 96.8)
Year 15 (N= 74;88)	87.2 (61.0 to 124.5)	69.6 (50.0 to 96.9)

Population analysed: Analysis was performes on subjects from the Long Term According-to-Protocol (LT ATP) cohort forimmunogenicity on anti-HBs seropositive subjects with available data at the specified time-points.

Primary outcome: Anti-HBs Anamnestic Response.

Time frame: One month after the challenge dose.. Number. Unit: Subjects

Measure	Twinrix Adult Group n = 8	Twinrix Junior Group n = 11
Value	8	10

Population analysed: Analysis was performed on Total Vaccinated cohort for challenge dose that included all subjects who received the challenge dose and for whom the immunogenicity data were available.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: SAEs: one month post challenge dose and up to Year 15 of the long-term follow-up, solicted symptoms: during the 4-day (Days 0-3) post challenge dose and unsolicited AEs: within the 31-day (Days 0-30) post challenge dose.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Twinrix Adult Group	1 of 102 (1%)	8 of 8 (100%)	Not reported
Twinrix Junior Group	0 of 113 (0%)	7 of 11 (63.6%)	Not reported

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 complete retesting and reanalysis.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 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.
Derived from this study: PubMed 27105563Beran J, Van Der Meeren O, Leyssen M, D'silva P. Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine. Vaccine. 2016 May 23;34(24):2686-91. doi: 10.1016/j.vaccine.2016.04.033. Epub 2016 Apr 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

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 Blood sampling and Additional challenge dose in people with Hepatitis B and Hepatitis A, 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 10 inclusion and 15 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 20 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 5 Jul 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-HAV Antibody Concentrations (time frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084). The study lists 5 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 NCT00875485, which also lists 2 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 20 Aug 2018.