Hepatitis BPhase 4NCT01138098
Evaluation of Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in Previously Vaccinated Children
A Phase 4 study testing Engerix™-B in people with Hepatitis B, run by GlaxoSmithKline at 11 sites in Slovakia.
Trial summary
This study will evaluate the persistence of immunity to hepatitis B 10 to 11 years after vaccination with Infanrix hexa™ or Engerix™-B and also the ability to mount an immune response to the challenge dose of Engerix™-B. Read more about this study
- Who is it for?
- Ages 11 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Engerix™-B
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 185 participants
- Where
- 11 sitesSlovakia
- Study dates
- 7 Jun 2010to 26 Nov 2010
- 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 11 to 12 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Subjects who the investigator believes that their parents/Legally acceptable representative) can and will comply with the requirements of the protocol should be enrolled in the study.
- A male or female aged 11-12 years at the time of study entry (from and including the 11th birthday until and excluding the 13th birthday).
- Written informed consent obtained from the parent or Legally Acceptable Representative of the subject.
- Study procedures will be explained to subjects and depending on their understanding, optional informed assent will be sought at the discretion of the investigator.
- Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/ Legally Acceptable Representative (s).
- Healthy subjects as established by medical history and clinical examination before entering into the study.
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- Subjects who have received all three doses of Infanrix hexa or Engerix-B in the primary study 217744/031 (NCT01457495).
- 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 during the entire treatment period and for 2 months after completion of the vaccination series.
Who cannot join
- Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
- Child in care.
- Use of any investigational or non-registered product drug or vaccine) other than the study vaccine within 30 days preceding the challenge dose of HBV vaccine, or planned use during the study period.
- Receipt of hepatitis B (containing) vaccine after vaccination in the primary study 217744/031 (NCT01457495).
- History of hepatitis B disease.
- Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before and ending 30 days after the HBV vaccine challenge dose.
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- Administration of immunoglobulins and/or any blood products within the three months preceding the challenge dose of HBV vaccine or planned administration during the study period.
- Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose of HBV vaccine.
- Pregnant or lactating female.
- Female planning to become pregnant or planning to discontinue contraceptive precautions.
- Known hypersensitivity to any component of the HBV vaccine or evidence of hypersensitivity after previous immunisation with a vaccine containing the hepatitis B component.
- Acute disease and/or fever at the time of enrolment.
- Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting
- Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Slovakia11 sites
GSK Investigational Site
Banská Bystrica, 974 01
GSK Investigational Site
Dolný Kubín, 026 01
GSK Investigational Site
Dubnica nad Váhom, 018 41
GSK Investigational Site
Martin, 036 01
GSK Investigational Site
Nitra, 949 01
GSK Investigational Site
Nová Dubnica, 018 51
GSK Investigational Site
Nové Zámky, 940 01
GSK Investigational Site
Púchov, 020 01
GSK Investigational Site
Rožňava, 048 01
GSK Investigational Site
Trebišov, 075 01
GSK Investigational Site
Zlaté Moravce, 953 01
About this study
Official title: Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in 11-12 Year Old Children, Previously Vaccinated With DTPa-HBV-IPV/Hib Vaccine in Study 217744/031
This study will evaluate the persistence of immunity to hepatitis B 10 to 11 years after vaccination with Infanrix hexa™ or Engerix™-B and also the ability to mount an immune response to the challenge dose of Engerix™-B.
Read the detailed description
Subjects who participated in the primary study 217744/031 (NCT01457495) will be invited at the age of 11-12 years to participate in this follow-up study.
- Conditions
- Hepatitis B
- Being tested
- Engerix™-B
- Keywords
- Persistence, challenge dose, Engerix-B, immune response
- 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™-BBiological
Intramuscular, single dose
| Study group | Role | What they receive |
|---|---|---|
| Infanrix-hexa/Engerix-B Group | Experimental | Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (217744/031 (NCT01457495)) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm. Receives: Biological: Engerix™-B |
| Infanrix-IPV+Hib/Engerix-B Group | Active comparator | Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (217744/031 (NCT01457495)) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm. Receives: Biological: Engerix™-B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL)
A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.
Measured: One month after a challenge dose of Engerix-B vaccine
Secondary outcomes (8)
Number of Subjects With an Anamnestic Response to a Challenge Dose
The anamnestic response was defined as: at least (≥) a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in seronegative subjects at the pre-challenge dose time point. A seropositive/seronegative subject is a subject with anti-HBs antibody concentration ≥/lower than (<) 6.2 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off.
Measured: Before and one month after a challenge dose of Engerix-B vaccine
Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL
A seropositive subject was defined as a subject with anti-HBs antibody concentration ≥ the 6.2 mIU/mLcut-off. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off.
Measured: Before and one month after a challenge dose of Engerix-B vaccine
Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL
A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.
Measured: Before and one month after a challenge dose of Engerix-B vaccine
Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL
A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.
Measured: Before the challenge dose of Engerix-B vaccine
Number of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed were pain, redness and swelling.
Measured: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine
Number of Subjects Reporting Solicited General Symptoms
Solicited general symptoms assessed were fatigue, gastrointestinal, headache and temperature (Temperature is defined as axillary temparature equal to or above 37.5 degrees Celsius (°C)).
Measured: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
An unsolicited adverse event is any adverse event (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.
Measured: During the 31-day (Days 0-30) follow-up period after a challenge dose of Engerix-B vaccine
Number of Subjects Reporting Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
Measured: After the challenge dose of Engerix-B vaccine up to the study end
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2010 (estimated)
- Study start7 Jun 2010
- Primary completion26 Nov 2010
- Study completion26 Nov 2010
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 4
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01138098
- Sponsor's protocol ID
- 113954
- Status last verified
- Sep 2016
- First submitted
- 27 May 2010
- 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
Avdicova M, Crasta PD, Hardt K, Kovac M. Lasting immune memory against hepatitis B following challenge 10-11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11-12 months of age. Vaccine. 2015 May 28;33(23):2727-33. doi: 10.1016/j.vaccine.2014.06.070. Epub 2014 Jun 22.
PubMed 24962750
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
- Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in 11-12 Year Old Children, Previously Vaccinated With DTPa-HBV-IPV/Hib Vaccine in Study 217744/031
- ClinicalTrials.gov ID
- NCT01138098
- Acronym / sponsor ID
- 113954
- Conditions
- Hepatitis B
- Keywords
- Persistence, challenge dose, Engerix-B, immune response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 7 Jun 2010
- Primary completion
- 26 Nov 2010 (actual)
- Study completion
- 26 Nov 2010 (actual)
- First posted
- 7 Jun 2010 (estimated)
- Results
- Posted 21 Dec 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the persistence of immunity to hepatitis B 10 to 11 years after vaccination with Infanrix hexa™ or Engerix™-B and also the ability to mount an immune response to the challenge dose of Engerix™-B.
Detailed description
Subjects who participated in the primary study 217744/031 (NCT01457495) will be invited at the age of 11-12 years to participate in this follow-up study.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infanrix-hexa/Engerix-B Group | Experimental | Biological: Engerix™-BSubjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (217744/031 (NCT01457495)) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm. |
| Infanrix-IPV+Hib/Engerix-B Group | Active comparator | Biological: Engerix™-BSubjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (217744/031 (NCT01457495)) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm. |
Who may qualify
- Ages
- 11 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- Subjects who the investigator believes that their parents/Legally acceptable representative) can and will comply with the requirements of the protocol should be enrolled in the study.
- A male or female aged 11-12 years at the time of study entry (from and including the 11th birthday until and excluding the 13th birthday).
- Written informed consent obtained from the parent or Legally Acceptable Representative of the subject.
- Study procedures will be explained to subjects and depending on their understanding, optional informed assent will be sought at the discretion of the investigator.
- Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/ Legally Acceptable Representative (s).
Key exclusion criteria (14 listed)
- Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
- Child in care.
- Use of any investigational or non-registered product drug or vaccine) other than the study vaccine within 30 days preceding the challenge dose of HBV vaccine, or planned use during the study period.
- Receipt of hepatitis B (containing) vaccine after vaccination in the primary study 217744/031 (NCT01457495).
- History of hepatitis B disease.
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™-BIntramuscular, single dose | Biological | Infanrix-IPV+Hib/Engerix-B Group, Infanrix-hexa/Engerix-B Group |
Primary outcome
Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL)
Time frame: One month after a challenge dose of Engerix-B vaccine
A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis.
8 secondary outcomes
Number of Subjects With an Anamnestic Response to a Challenge Dose
Time frame: Before and one month after a challenge dose of Engerix-B vaccine
Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL
Time frame: Before and one month after a challenge dose of Engerix-B vaccine
Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL
Time frame: Before and one month after a challenge dose of Engerix-B vaccine
Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL
Time frame: Before the challenge dose of Engerix-B vaccine
Number of Subjects Reporting Solicited Local Symptoms
Time frame: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine
Number of Subjects Reporting Solicited General Symptoms
Time frame: During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Time frame: During the 31-day (Days 0-30) follow-up period after a challenge dose of Engerix-B vaccine
Number of Subjects Reporting Serious Adverse Events (SAEs)
Time frame: After the challenge dose of Engerix-B vaccine up to the study end
Results and safety
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 24962750Avdicova M, Crasta PD, Hardt K, Kovac M. Lasting immune memory against hepatitis B following challenge 10-11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11-12 months of age. Vaccine. 2015 May 28;33(23):2727-33. doi: 10.1016/j.vaccine.2014.06.070. Epub 2014 Jun 22.
- 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
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Engerix™-B in people with Hepatitis B, run by GlaxoSmithKline at 11 sites in Slovakia.
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 12 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 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 11 sites in Slovakia. 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 21 Dec 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 With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL) (time frame: One month after a challenge dose of Engerix-B vaccine). 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 NCT01138098, 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.