Hepatitis BPhase 3NCT00197184

Long Term Follow-up Study at Years 2, 3, 4 and 5 Where 2 Dosing Schedules of the Combined Hepatitis A and B Vaccine Were Compared

A Phase 3 study testing Twinrix™ Adult and Twinrix™ Junior in people with Hepatitis B and Hepatitis A, run by GlaxoSmithKline at 7 sites in 3 countries.

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

To evaluate the persistence of anti-hepatitis A virus (HAV) and anti-hepatitis B surface antigen (HBs) antibodies up to 2, 3, 4 and 5 years after administration of the first dose of the study vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. Read more about this study

Who is it for?: Ages 3 to 13 yearsHealthy volunteers can take part
Conditions the study is for: Hepatitis B, Hepatitis A
What is being tested?: Twinrix™ Adult and Twinrix™ Junior
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 276 participants
Where: 7 sitesin 3 countries
Study dates: 1 Nov 2003to 10 Mar 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 3 to 13 years
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Participation in primary study
Written informed consent obtained before each long term follow up visit.

Who cannot join

None listed.

Trial locations and contacts

7 sites in 3 countries.

Country

City, postcode or hospital

7 sites in 3 countries

Spain4 sites

GSK Investigational Site
Barcelona, 08042
GSK Investigational Site
Blanes (Girona), 17300
GSK Investigational Site
Cerdanyola Del Vallés / Barcelona, 08290
GSK Investigational Site
Valencia, 46024

Other trials in Spain

Australia2 sites

GSK Investigational Site
Carlton, Victoria, 3053
GSK Investigational Site
North Adelaide, South Australia, 5006

Other trials in Australia

Belgium1 site

GSK Investigational Site
Brussels, 1200

Other trials in Belgium

About this study

Official title: Evaluate the Persistence of Immune Response of GSK Biologicals' Twinrix™ Vaccine, Administered According to a 0,6 Month Schedule and a 0,1,6 Month Schedule, in Healthy Children Aged Between 1-11 Years at the Time of First Vaccine Dose

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Read the detailed description

Open, randomised, self-contained, multicentric, multinational, long-term antibody persistence studies. Immune persistence was compared between subjects who received either two dose or three doses of GSK Biologicals combined hepatitis A and hepatitis B vaccine. The long-term follow-up studies involved taking blood samples at approximately 2, 3, 4 and 5 years after the primary vaccination of combined hepatitis A and B vaccine to assess antibody persistence. No additional subjects will be recruited during the long term follow-up period.

Conditions: Hepatitis B, Hepatitis A
Being tested: Twinrix™ Adult, Twinrix™ Junior
Keywords: Combined hepatitis A and B vaccine, Twinrix™
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™ AdultBiological
Also called Combined hepatitis A and B vaccine
Intramuscular injection in the left deltoid, 2 doses, Adult formulation in primary study.
Twinrix™ JuniorBiological
Also called Combined hepatitis A and B vaccine
Intramuscular injection in the left deltoid, 3 doses, junior formulation in primary study.

Study groups in NCT00197184
Study group	Role	What they receive
Twinrix Junior	Experimental	Subjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation). Receives: Biological: Twinrix™ Junior
Twinrix Adult	Active comparator	Subjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation). Receives: Biological: Twinrix™ Adult

What is being measured

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

Anti-hepatitis A (HAV) Antibody Concentrations
Geometric mean concentration for anti-HAV antibodies expressed as Milli-International Units per milliliter (mIU/mL)
Measured: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)
Anti-hepatitis B (HBs) Antibody Concentrations
Geometric mean concentration for anti-HBs antibodies expressed as Milli-International Units per milliliter (mIU/mL).
Measured: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)
Anti-HAV Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.
Any subjects becoming seronegative for anti-HAV antibodies (i.e. titres < 15 mIU/ml) at any long term time point, were to receive an additional vaccine dose administered between 6 to 12 months after Year 5 time point.
Measured: Before and one month after additional vaccination
Anti-HBs Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.
Subjects losing seroprotective anti-HBs antibody titres (i.e. titres < 10 mIU/ml) at any long term time point, received an Engerix challenge dose. The table presents the geometric mean concentrations for anti-HBs antibodies, expressed as Milli-International Units per milliliter (mIU/mL).
Measured: Before and One month after additional vaccination

Secondary outcomes (5)

Number of Subjects Reporting Serious Adverse Events (SAEs) Determined by the Investigator to Have a Causal Relationship to Primary Vaccination or Due to Lack of Vaccine Efficacy.
A serious adverse event (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: From last study visit of the primary study up to Year 5 long term follow-up
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Solicited local symptoms assessed include pain, redness and swelling at the vaccine injection site.
Any= regardless of intensity grade; Grade 3 Pain= spontaneously painful
Measured: during the 4-day follow-up period after additional vaccination
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache.
Any= regardless of intensity grade or relationship to vaccination; grade 3= prevented normal activity; Related= considered by the investigator to be causally related to the vaccination
Measured: During the 4-day follow-up period after additional vaccination
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Unsolicited Adverse Events (AEs).
An Adverse Event is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: During the 30-day follow-up period after additional vaccination.
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Any Serious Adverse Events
A serious adverse event (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: At least one month after additional vaccination

Timeline

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

1 Nov 200310 Mar 2004

First posted20 Sep 2005 (estimated)
Study start1 Nov 2003
Primary completion10 Mar 2004
Study completion10 Mar 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 (1)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: 276 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00197184
Sponsor's protocol ID: 208127/132 (EXT Y2)
Other IDs: 208127/133 (EXT Y3), 208127/134 (EXT Y4), 208127/137 (EXT Y5)
Status last verified: Oct 2016
First submitted: 15 Sep 2005
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

Marshall H, Nolan T, Diez Domingo J, Rombo L, Sokal EM, Mares J, Casanovas JM, Kuriyakose S, Leyssen M, Jacquet JM. Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1-11 years. Vaccine. 2010 Jun 17;28(27):4411-5. doi: 10.1016/j.vaccine.2010.04.040. Epub 2010 Apr 29.
PubMed 20434544

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

Active, not recruitingPhase 1/2
A Clinical Study of HT-101 and/or HT-102 in Patients With Chronic Hepatitis B Virus Infection
Chronic Hepatitis B
Active, not recruitingPhase 2
A Clinical Study of HT-101 and HT-102 in Patients With Chronic Hepatitis B Virus Infection
Chronic Hepatitis B
Not yet recruitingPhase 1
Phase Ia/Ib Trial of SCTA02A Injection in Healthy Adults and Patients With Chronic Hepatitis B
Hepatitis B
Recruiting
HIV/HBV/HCV Triple Screening in Primary Care
HIV, HBV (Hepatitis B Virus)
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C

All Hepatitis B trials

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: Evaluate the Persistence of Immune Response of GSK Biologicals' Twinrix™ Vaccine, Administered According to a 0,6 Month Schedule and a 0,1,6 Month Schedule, in Healthy Children Aged Between 1-11 Years at the Time of First Vaccine Dose
ClinicalTrials.gov ID: NCT00197184
Acronym / sponsor ID: 208127/132 (EXT Y2)
Conditions: Hepatitis B, Hepatitis A
Keywords: Combined hepatitis A and B vaccine, Twinrix™
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 276 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 1 Nov 2003
Primary completion: 10 Mar 2004 (actual)
Study completion: 10 Mar 2004 (actual)
First posted: 20 Sep 2005 (estimated)
Results: Posted 4 Jun 2009

Clinical summary

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

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed description

Study design

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

Arm	Type	Receives
Twinrix Junior	Experimental	Biological: Twinrix™ JuniorSubjects previously received 3 doses of combined hepatitis A / hepatitis B vaccine (junior formulation).
Twinrix Adult	Active comparator	Biological: Twinrix™ AdultSubjects previously received 2 doses of combined hepatitis A / hepatitis B vaccine (adult formulation).

Who may qualify

Ages: 3 to 13 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (2 listed)

Participation in primary study
Written informed consent obtained before each long term follow up visit.

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™ AdultAlso: Combined hepatitis A and B vaccineIntramuscular injection in the left deltoid, 2 doses, Adult formulation in primary study.	Biological	Twinrix Adult
Twinrix™ JuniorAlso: Combined hepatitis A and B vaccineIntramuscular injection in the left deltoid, 3 doses, junior formulation in primary study.	Biological	Twinrix Junior

Primary outcome

Anti-hepatitis A (HAV) Antibody Concentrations
Time frame: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)
Geometric mean concentration for anti-HAV antibodies expressed as Milli-International Units per milliliter (mIU/mL)
Anti-hepatitis B (HBs) Antibody Concentrations
Time frame: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)
Geometric mean concentration for anti-HBs antibodies expressed as Milli-International Units per milliliter (mIU/mL).
Anti-HAV Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.
Time frame: Before and one month after additional vaccination
Any subjects becoming seronegative for anti-HAV antibodies (i.e. titres < 15 mIU/ml) at any long term time point, were to receive an additional vaccine dose administered between 6 to 12 months after Year 5 time point.
Anti-HBs Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.
Time frame: Before and One month after additional vaccination
Subjects losing seroprotective anti-HBs antibody titres (i.e. titres < 10 mIU/ml) at any long term time point, received an Engerix challenge dose. The table presents the geometric mean concentrations for anti-HBs antibodies, expressed as Milli-International Units per milliliter (mIU/mL).

5 secondary outcomes

Number of Subjects Reporting 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: From last study visit of the primary study up to Year 5 long term follow-up
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited Local Symptoms
Time frame: during the 4-day follow-up period after additional vaccination
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Solicited General Symptoms.
Time frame: During the 4-day follow-up period after additional vaccination
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Unsolicited Adverse Events (AEs).
Time frame: During the 30-day follow-up period after additional vaccination.
Number of Subjects Receiving an Additional Vaccine Dose and Reporting Any Serious Adverse Events
Time frame: At least one month after additional vaccination

Results and safety

Results posted to the registry on 4 Jun 2009, 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	139	139
Twinrix Junior	137	137

Primary outcome: Anti-hepatitis A (HAV) Antibody Concentrations

Time frame: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60). Geometric mean (95% Confidence Interval). Unit: mIU/mL

Measure	Twinrix Adult n = 129	Twinrix Junior n = 119
At year 2	1122.2 (937.7 to 1343.0)	1377.8 (1114.0 to 1704.2)
At year 3	998.6 (845.8 to 1178.9)	1347.1 (1145.1 to 1584.8)
At year 4	737.5 (623.6 to 872.3)	915.9 (774.0 to 1084.0)
At year 5	576.8 (473.6 to 702.5)	698.4 (585.1 to 833.7)

Population analysed: Analysis was performed on the Long Term According to Protocol cohort for analysis of immunogenicity (LT ATP immunogenicity cohort) which included all subjects that complied with the protocol and for whom data concerning immunogenicity endpoint measures were available for the particular time point measured.

Primary outcome: Anti-hepatitis B (HBs) Antibody Concentrations

Time frame: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60). Geometric mean (95% Confidence Interval). Unit: mIU/mL

Measure	Twinrix Adult n = 129	Twinrix Junior n = 119
At year 2	479.9 (356.6 to 646.0)	830.6 (609.5 to 1131.9)
At year 3	325.1 (244.7 to 431.8)	695.1 (516.5 to 935.5)
At year 4	270.2 (201.0 to 363.3)	519.7 (378.5 to 713.6)
At year 5	150.2 (110.5 to 204.3)	283.7 (208.6 to 386.0)

Primary outcome: Anti-HAV Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.

Time frame: Before and one month after additional vaccination

Population analysed: None of the subjects became seronegative for anti-HAV antibodies during the Year 2 to Year 5 long term follow-up. Hence none of the subjects received an additional Havrix dose.

Primary outcome: Anti-HBs Antibody Concentrations in Subjects Receiving the Additional Vaccine Dose.

Time frame: Before and One month after additional vaccination. Geometric mean (95% Confidence Interval). Unit: mIU/mL

Measure	Twinrix Adult n = 11	Twinrix Junior n = 5
Before vaccination	4.9 (2.1 to 11.1)	2.4 (0.9 to 6.5)
Post vaccination	521.3 (158.2 to 1718.1)	509.7 (173.5 to 1497.9)

Population analysed: Analysis was performed on the Total vaccinated cohort for the challenge dose, including all subjects who received an additional vaccine dose between 6 to 12 months after year 5.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited symtoms: During the 4-day (Day 0-3) follow-up period after the additional vaccination. Unsolicited AEs: During the 31-day (Day 0-30) period after the additional vaccination; SAEs: During the entire study period. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Twinrix Adult	0 of 139 (0%)	7 of 11 (63.6%)	Not reported
Twinrix Junior	0 of 137 (0%)	0 of 5 (0%)	Not reported

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.
Background: PubMed 20434544Marshall H, Nolan T, Diez Domingo J, Rombo L, Sokal EM, Mares J, Casanovas JM, Kuriyakose S, Leyssen M, Jacquet JM. Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1-11 years. Vaccine. 2010 Jun 17;28(27):4411-5. doi: 10.1016/j.vaccine.2010.04.040. Epub 2010 Apr 29.
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.

Related trials for Hepatitis B

Active, not recruitingPhase 1/2
A Clinical Study of HT-101 and/or HT-102 in Patients With Chronic Hepatitis B Virus Infection
Chronic Hepatitis B
Active, not recruitingPhase 2
A Clinical Study of HT-101 and HT-102 in Patients With Chronic Hepatitis B Virus Infection
Chronic Hepatitis B
Not yet recruitingPhase 1
Phase Ia/Ib Trial of SCTA02A Injection in Healthy Adults and Patients With Chronic Hepatitis B
Hepatitis B
Recruiting
HIV/HBV/HCV Triple Screening in Primary Care
HIV, HBV (Hepatitis B Virus)
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C

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

7 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Twinrix™ Adult and Twinrix™ Junior in people with Hepatitis B and Hepatitis A, run by GlaxoSmithKline at 7 sites in 3 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 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 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 7 sites in Spain, Australia, 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 4 Jun 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?

Anti-hepatitis A (HAV) Antibody Concentrations (time frame: Year 2 (Month 24), Year 3 (Month 36), Year 4 (Month 48) and Year 5 (Month 60)). The study lists 4 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 NCT00197184, 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 20 Aug 2018.