Hepatitis BPhase 3NCT00343915

Immuno & Safety Study of GSK Biologicals' Thio or Preservative Free Hepatitis B Vaccine in Subjects Aged 11-15 Yrs

A Phase 3 study testing Engerix™-B (thiomersal-free) 20µg and 10 μg Engerix™-B (preservative-free) in people with Hepatitis B, run by GlaxoSmithKline at 4 sites in 3 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

To evaluate the persistence of antibodies against hepatitis B at 30, 42, 54 and 66 months after the first dose of the hepatitis B primary vaccination course. Subjects were aged 11 to 15 years at the time of the primary vaccination course. Read more about this study

Who is it for?: Ages 13 to 20 yearsHealthy volunteers can take part
Conditions the study is for: Hepatitis B
What is being tested?: Engerix™-B (thiomersal-free) 20µg and 10 μg Engerix™-B (preservative-free)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 267 participants
Where: 4 sitesin 3 countries
Study dates: 21 Apr 2004to 10 Jan 2008
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 13 to 20 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

Subjects have participated in primary study HBV-280
Written informed consent will be obtained from each subject and/ or parent or guardian of the subject before the blood-sampling visit of each year

Who cannot join

None listed.

Trial locations and contacts

4 sites in 3 countries.

Country

City, postcode or hospital

4 sites in 3 countries

Belgium2 sites

GSK Investigational Site
Brussels, 1200
GSK Investigational Site
Wilrijk, 2610

Other trials in Belgium

Australia1 site

GSK Investigational Site
Sydney, New South Wales

Other trials in Australia

Ukraine1 site

GSK Investigational Site
Kyiv, 03038

Other trials in Ukraine

About this study

Official title: Long-term Study of Immune Response Persistence of GSK Biologicals' 2-dose Thiomersal-free Engerix™-B and 3-dose Preservative-free Engerix™-B Vaccines in Subjects Aged 11-15 Yrs

To evaluate the persistence of antibodies against hepatitis B at 30, 42, 54 and 66 months after the first dose of the hepatitis B primary vaccination course.

Subjects were aged 11 to 15 years at the time of the primary vaccination course.

At the time of enrollment in the present long-term follow-up study subjects were aged 13 to 18 years.

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

Read the detailed description

All subjects who participated in the primary study, in which they received either 2 or 3 doses of GSK Biologicals hepatitis B vaccine, and who consented to participate in the long-term follow-up at Month 42 were contacted by the investigators.

No additional subjects will be recruited during this long-term follow-up study and no vaccine will be administered.

Conditions: Hepatitis B
Being tested: Engerix™-B (thiomersal-free) 20µg, 10 μg Engerix™-B (preservative-free), placebo
Keywords: Persistence, Hepatitis B vaccine
Medical subject headings: Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Engerix™-B (thiomersal-free) 20µgBiological
In the primary study: 2 deep intramuscular injections (Months 0, \& 6)
10 μg Engerix™-B (preservative-free)Biological
In the primary study: 3 deep intramuscular injections (months 0, 1 \& 6)
placeboBiological
In the primary study: 1 deep intramuscular injection (month 1)

Study groups in NCT00343915
Study group	Role	What they receive
2-Dose Engerix	Experimental	subjects received 2 doses of adult (thiomersal-free) HBV formulation, one at 0 and 6 months, respectively and placebo (physiological saline) at 1 month. Receives: Biological: Engerix™-B (thiomersal-free) 20µg; Biological: placebo
3-Dose Engerix	Active comparator	subjects received 3 doses of paediatric (preservative-free) HBV formulation one at 0, 1 and 6 months, respectively. Receives: Biological: 10 μg Engerix™-B (preservative-free)

What is being measured

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

Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.
A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.
Measured: At Month 7
Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.
A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.
Measured: At Month 30, Month 42, Month 54 and Month 66
Antibody Titers Against Hepatitis-B Virus.
Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs.
Measured: At Month 30, Month 42, Month 54 and Month 66

Secondary outcomes (7)

Antibody Titers Against Hepatitis-B Virus.
Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs.
Measured: At Months 1, 2, 6 and 7
Number of Subjects Seroprotected for Anti-HBs Antibody.
A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.
Measured: At Months 1, 2 and 6
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
Measured: During the 4-day (Day 0-3) follow-up period after each vaccination and overall
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, and fever. Any was defined as incidence of the specified symptoms regardless of intensity or relationship to study vaccine. Gastrointestinal symptoms included nausea, vomiting, diarrhea and abdominal pain. Grade 3 fever was defined as fever (axillary temperature) > 38.5°C. Grade 3 symptoms were defined as symptoms which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the vaccination.
Measured: During the 4-day (Day 0-3) follow-up period after each vaccination and overall
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE).
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.
Measured: During the 31-day (Day 0-30) follow-up period after each vaccination and overall
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include 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: During the entire study period (Month 0 to Month 66)
Number of Subjects With Serious Adverse Events (SAEs).
erious adverse events (SAEs) assessed include 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: At Month 30, Month 42, Month 54 & Month 66

Timeline

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

21 Apr 200410 Jan 2008

First posted23 Jun 2006 (estimated)
Study start21 Apr 2004
Primary completion10 Jan 2008
Study completion10 Jan 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 (3)Papers the sponsor has linked to this study.
Other trials for Hepatitis BStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 267 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00343915
Sponsor's protocol ID: 101695 Ext. Mth30
Other IDs: 101696, 101697, 101698, 2015-001531-20, 2015
Status last verified: Feb 2019
First submitted: 14 Sep 2005
Last updated: 10 Jun 2019
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

Heron L, Selnikova O, Moiseieva A, Van Damme P, van der Wielen M, Levie K, Hoet B, Stoffel M. Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11-15 years: a randomised controlled trial. Vaccine. 2007 Apr 12;25(15):2817-22. doi: 10.1016/j.vaccine.2006.12.021. Epub 2006 Dec 29.
PubMed 17276552
Heron LG, Chant KG, Jalaludin BB. A novel hepatitis B vaccination regimen for adolescents: two doses 12 months apart. Vaccine. 2002 Oct 4;20(29-30):3472-6. doi: 10.1016/s0264-410x(02)00346-8.
PubMed 12297392
Van Damme P, Moiseeva A, Marichev I, Kervyn AD, Booy R, Kuriyakose S, Brockway A, Ng SP, Leyssen M, Jacquet JM. Five years follow-up following two or three doses of a hepatitis B vaccine in adolescents aged 11-15 years: a randomised controlled study. BMC Infect Dis. 2010 Dec 20;10:357. doi: 10.1186/1471-2334-10-357.
PubMed 21171982

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 10 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Long-term Study of Immune Response Persistence of GSK Biologicals' 2-dose Thiomersal-free Engerix™-B and 3-dose Preservative-free Engerix™-B Vaccines in Subjects Aged 11-15 Yrs
ClinicalTrials.gov ID: NCT00343915
Acronym / sponsor ID: 101695 Ext. Mth30
Conditions: Hepatitis B
Keywords: Persistence, Hepatitis B vaccine
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 267 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 21 Apr 2004 (actual)
Primary completion: 10 Jan 2008 (actual)
Study completion: 10 Jan 2008 (actual)
First posted: 23 Jun 2006 (estimated)
Results: Posted 31 Mar 2009

Clinical summary

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

To evaluate the persistence of antibodies against hepatitis B at 30, 42, 54 and 66 months after the first dose of the hepatitis B primary vaccination course.

Subjects were aged 11 to 15 years at the time of the primary vaccination course.

At the time of enrollment in the present long-term follow-up study subjects were aged 13 to 18 years.

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

Detailed description

No additional subjects will be recruited during this long-term follow-up study and no vaccine will be administered.

Study design

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

Arm	Type	Receives
2-Dose Engerix	Experimental	Biological: Engerix™-B (thiomersal-free) 20µg, Biological: placebosubjects received 2 doses of adult (thiomersal-free) HBV formulation, one at 0 and 6 months, respectively and placebo (physiological saline) at 1 month.
3-Dose Engerix	Active comparator	Biological: 10 μg Engerix™-B (preservative-free)subjects received 3 doses of paediatric (preservative-free) HBV formulation one at 0, 1 and 6 months, respectively.

Who may qualify

Ages: 13 to 20 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (2 listed)

Subjects have participated in primary study HBV-280
Written informed consent will be obtained from each subject and/ or parent or guardian of the subject before the blood-sampling visit of each year

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Engerix™-B (thiomersal-free) 20µgIn the primary study: 2 deep intramuscular injections (Months 0, \& 6)	Biological	2-Dose Engerix
10 μg Engerix™-B (preservative-free)In the primary study: 3 deep intramuscular injections (months 0, 1 \& 6)	Biological	3-Dose Engerix
placeboIn the primary study: 1 deep intramuscular injection (month 1)	Biological	2-Dose Engerix

Primary outcome

Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.
Time frame: At Month 7
A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.
Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.
Time frame: At Month 30, Month 42, Month 54 and Month 66
A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.
Antibody Titers Against Hepatitis-B Virus.
Time frame: At Month 30, Month 42, Month 54 and Month 66
Antibody titers were summarized by Geometric Mean Concentrations (GMCs) with their 95% CIs.

7 secondary outcomes

Antibody Titers Against Hepatitis-B Virus.
Time frame: At Months 1, 2, 6 and 7
Number of Subjects Seroprotected for Anti-HBs Antibody.
Time frame: At Months 1, 2 and 6
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 4-day (Day 0-3) follow-up period after each vaccination and overall
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.
Time frame: During the 4-day (Day 0-3) follow-up period after each vaccination and overall
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AE).
Time frame: During the 31-day (Day 0-30) follow-up period after each vaccination and overall
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: During the entire study period (Month 0 to Month 66)
Number of Subjects With Serious Adverse Events (SAEs).
Time frame: At Month 30, Month 42, Month 54 & Month 66

Results and safety

Results posted to the registry on 31 Mar 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
2-dose Engerix	258	254
3-dose Engerix	126	123

Primary outcome: Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.

Time frame: At Month 7. Number. Unit: Subjects

Measure	2-dose Engerix n = 241	3-dose Engerix n = 113
Value	233	111

Population analysed: The ATP cohort for immunogenicity included all evaluable subjects who had post-vaccination immunogenicity results and who complied with the protocol, including the time schedule for vaccination and blood sample draw.

Primary outcome: Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody.

Time frame: At Month 30, Month 42, Month 54 and Month 66. Number. Unit: Subjects

Measure	2-dose Engerix n = 166	3-dose Engerix n = 80
Month 30 (N=140, 64)	122	62
Month 42 (N=166, 80)	139	74
Month 54 (N=147, 76)	124	72
Month 66 (N=132, 70)	105	64

Population analysed: Long Term According-to-Protocol cohort for immunogenicity, including all subjects who returned at the considered follow-up time point and who complied with the protocol.

Primary outcome: Antibody Titers Against Hepatitis-B Virus.

Time frame: At Month 30, Month 42, Month 54 and Month 66. Geometric mean (95% Confidence Interval). Unit: mIU/mL

Measure	2-dose Engerix n = 166	3-dose Engerix n = 80
Month 30 (N=140, 64)	229.0 (162.1 to 323.5)	708.3 (409.6 to 1224.8)
Month 42 (N=166, 80)	159.7 (118.3 to 215.7)	417.9 (267.3 to 653.6)
Month 54 (N=147, 76)	123.6 (92.7 to 165.0)	277.6 (176.5 to 436.7)
Month 66 (N=132, 70)	82.1 (60.7 to 111.0)	225.2 (142.6 to 355.9)

Population analysed: Long Term According-to-Protocol cohort for immunogenicity, including all subjects who returned at the considered follow-up time point and who complied with the protocol.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events: during the entire study period (Month 0-66), Solicited local and general symptoms: During the 4-day (Days 0-3) post vaccination period and unsolicited adverse events: up to Month 7.Non-serious adverse events were not assessed during the long term follow-up period (Month 30-66). The total number of participants at risk is the number of participants with at least one documented dose.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
2-dose Engerix	4 of 257 (1.6%)	155 of 257 (60.3%)	0 of 257
3-dose Engerix	1 of 125 (0.8%)	74 of 125 (59.2%)	0 of 125

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17276552Heron L, Selnikova O, Moiseieva A, Van Damme P, van der Wielen M, Levie K, Hoet B, Stoffel M. Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11-15 years: a randomised controlled trial. Vaccine. 2007 Apr 12;25(15):2817-22. doi: 10.1016/j.vaccine.2006.12.021. Epub 2006 Dec 29.
Background: PubMed 12297392Heron LG, Chant KG, Jalaludin BB. A novel hepatitis B vaccination regimen for adolescents: two doses 12 months apart. Vaccine. 2002 Oct 4;20(29-30):3472-6. doi: 10.1016/s0264-410x(02)00346-8.
Background: PubMed 21171982Van Damme P, Moiseeva A, Marichev I, Kervyn AD, Booy R, Kuriyakose S, Brockway A, Ng SP, Leyssen M, Jacquet JM. Five years follow-up following two or three doses of a hepatitis B vaccine in adolescents aged 11-15 years: a randomised controlled study. BMC Infect Dis. 2010 Dec 20;10:357. doi: 10.1186/1471-2334-10-357.
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

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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

4 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 Engerix™-B (thiomersal-free) 20µg and 10 μg Engerix™-B (preservative-free) in people with Hepatitis B, run by GlaxoSmithKline at 4 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 10 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Belgium, Australia, Ukraine. 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 31 Mar 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 Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody. (time frame: At Month 7). The study lists 3 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 NCT00343915, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2019.