Hepatitis BPhase 4NCT01451801
Cellular Immunity in Adult Hepatitis B-vaccinated Serologic Non-responders
A Phase 4 study testing Twinrix in people with Hepatitis B, run by University of Aarhus at 1 site in Denmark.
Trial summary
Previous studies have shown that 5-10% of Hepatitis B Virus vaccine recipients produce none or to few antibodies after a standard immunization with 3 vaccines. These individuals are defined as non-responders. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Twinrix
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteDenmark
- Study dates
- Oct 2011to Jul 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Signed participant information and consent
- Age over 18 years
- Women of childbearing potential must use effective contraceptives
Who cannot join
- previous HBV infection
- previous HBV immunization
- pregnancy (or planned pregnancy within 6 months)
- allergy to contents in the vaccine (formaldehyde).
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Infectious Diseases, Aarhus University Hospital
Aarhus N, 8200
About this study
Previous studies have shown that 5-10% of Hepatitis B Virus vaccine recipients produce none or to few antibodies after a standard immunization with 3 vaccines. These individuals are defined as non-responders. The investigators wish to investigate if mounting another kind of immune response, called the cellular immune (CMI) response, protects these non-responders.
Aim/Hypothesis
Read more
Primary aims:
- To estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization Secondary aims:
- To establish the prevalence of serological non-responders after a standard course of HBV vaccination.
- To assess the safety of the vaccine.
- Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization
- To compare the immunological profile before and after a standard HBV vaccination regimen on non-responders and responders
- Establish a rapid test for measuring CMI after being HBV vaccinated.
A total of 400 healthy volunteers receive a standard course of immunization with a combined hepatitis A and B vaccine (Twinrix®) at 0, 1, and 6 months. Blood is drawn at 0 and 8 months from all participants. The blood will be analysed to see if there is antibodies or/and if there is mounted a cellular immune response by measuring on parameters called cytokines.
- Conditions
- Hepatitis B
- Being tested
- Twinrix
- Keywords
- Hepatitis B, non responders, cellular immune response, cytokines, predictors, HBsAg
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TwinrixBiological
A total of 400 healthy volunteers receive a standard course of immunization with a combined hepatitis A and B vaccine (Twinrix®) at 0, 1, and 6 months.
Twinrix ® Adult suspension for injection. 1 ml contains 720 ELISA units of hepatitis A virus antigen adsorbed to aluminum hydroxide and 20 micrograms hepatitis B surface antigen (HBsAg) adsorbed to aluminum phosphate in sterile water. Excipient: sodium chloride. Contains traces of neomycin.
| Study group | Role | What they receive |
|---|---|---|
| HBsAg | Other | Not described Receives: Biological: Twinrix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization
Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-γ producing CD4+ T cells
Measured: within 9. month from 1. vaccination
Secondary outcomes (5)
Establish the prevalence of serological non-responders after a standard course of HBV vaccination defined by anti-HBs <10 mIU / ml
Antibodies to Hepatitis B surface antigen are detected by use of a comercially available kit at the department of Clinical Immunology, Aarhus University Hospital, Skejby
Measured: Within 9 month from 1. vaccination
Assess the safety of the vaccine by evaluating the numbers and intensity of adverse and Serious adverse events
By evaluating adverse events described in Case Report Forms
Measured: Within 9 month from 1. vaccination
Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization
Questionnaire and *Magnitude of HBsAg-specific cell-mediated immune response.The presence of antigen specifik single, double or triple cytokine-producing T cells. Numbers and fractions of antigen-specific CD4 and CD8 T cells *HBsAg-specific T cell proliferation is quantified*The difference in phenotypic T cell profiles is getting compared at baseline*HBsAg-specific B cells measured by flow cytometry with staining for surface markers*Supernatant from HBsAg-stimulated PBMC is analysed regarding cytokines* Production of pro- og antiinflammatory cytokines is assesed by RT-PCR .
Measured: within 9 month from 1. vaccination
Compare the immunological profile before and after a standard HBV vaccination regimen, with com-parison of serological non-responders and serological responders
Magnitude of HBsAg-specific cell-mediated immune response.The presence of antigen specifik single, double or triple cytokine-producing T cells. Numbers and fractions of antigen-specific CD4 and CD8 T cells *HBsAg-specific T cell proliferation is quantified*The difference in phenotypic T cell profiles is getting compared at baseline*HBsAg-specific B cells measured by flow cytometry with staining for surface markers*Supernatant from HBsAg-stimulated PBMC is analysed regarding cytokines* Production of pro- og antiinflammatory cytokines is assesed by RT-PCR .
Measured: Within 9. month from 1. vaccination
Establish a rapid test for measuring HBsAg specific CMI by use of an IFN-gamma based assay.
Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-γ producing CD4+ T cells
Measured: 18 month after 1. vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionJul 2013 (estimated)
- Study completionJul 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Monash Medical Centre
- Responsible party
- Sponsor
- Investigators
- Lars Østergaard, Head, Study chair, Department of Infectious Diseases, Aarhus University HospitalSøren Jensen-Fangel, MD, Study director, Department of Infectious Diseases, Aarhus University HospitalMartin Tolstrup, MSc, Study director, Department of Infectious Diseases, Aarhus University HospitalMaria B Pedersen, Bach.Med, Principal investigator, Department of Infectious Diseases, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01451801
- Sponsor's protocol ID
- SJF0001
- Status last verified
- Oct 2012
- First submitted
- 10 Oct 2011
- Last updated
- 26 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cellular Immunity in Adult Hepatitis B-vaccinated Serologic Non-responders
- ClinicalTrials.gov ID
- NCT01451801
- Acronym / sponsor ID
- SJF0001
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B, non responders, cellular immune response, cytokines, predictors, HBsAg
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Monash Medical Centre
- Study start
- Oct 2011
- Primary completion
- Jul 2013 (estimated)
- Study completion
- Jul 2013 (estimated)
- First posted
- 14 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Previous studies have shown that 5-10% of Hepatitis B Virus vaccine recipients produce none or to few antibodies after a standard immunization with 3 vaccines. These individuals are defined as non-responders. The investigators wish to investigate if mounting another kind of immune response, called the cellular immune (CMI) response, protects these non-responders.
Aim/Hypothesis
Primary aims:
- To estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization Secondary aims:
- To establish the prevalence of serological non-responders after a standard course of HBV vaccination.
- To assess the safety of the vaccine.
- Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization
- To compare the immunological profile before and after a standard HBV vaccination regimen on non-responders and responders
- Establish a rapid test for measuring CMI after being HBV vaccinated.
A total of 400 healthy volunteers receive a standard course of immunization with a combined hepatitis A and B vaccine (Twinrix®) at 0, 1, and 6 months. Blood is drawn at 0 and 8 months from all participants. The blood will be analysed to see if there is antibodies or/and if there is mounted a cellular immune response by measuring on parameters called cytokines.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBsAg | Other | Biological: Twinrix |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Signed participant information and consent
- Age over 18 years
- Women of childbearing potential must use effective contraceptives
Key exclusion criteria (4 listed)
- previous HBV infection
- previous HBV immunization
- pregnancy (or planned pregnancy within 6 months)
- allergy to contents in the vaccine (formaldehyde).
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 |
|---|---|---|
| TwinrixA total of 400 healthy volunteers receive a standard course of immunization with a combined hepatitis A and B vaccine (Twinrix®) at 0, 1, and 6 months. Twinrix ® Adult suspension for injection. 1 ml contains 720 ELISA units of hepatitis A virus antigen adsorbed to aluminum hydroxide and 20 micrograms hepatitis B surface antigen (HBsAg) adsorbed to aluminum phosphate in sterile water. Excipient: sodium chloride. Contains traces of neomycin. | Biological | HBsAg |
Primary outcome
Estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization
Time frame: within 9. month from 1. vaccination
Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-γ producing CD4+ T cells
5 secondary outcomes
Establish the prevalence of serological non-responders after a standard course of HBV vaccination defined by anti-HBs <10 mIU / ml
Time frame: Within 9 month from 1. vaccination
Assess the safety of the vaccine by evaluating the numbers and intensity of adverse and Serious adverse events
Time frame: Within 9 month from 1. vaccination
Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization
Time frame: within 9 month from 1. vaccination
Compare the immunological profile before and after a standard HBV vaccination regimen, with com-parison of serological non-responders and serological responders
Time frame: Within 9. month from 1. vaccination
Establish a rapid test for measuring HBsAg specific CMI by use of an IFN-gamma based assay.
Time frame: 18 month after 1. vaccination
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2012.
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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.
Lars Østergaard, Head study chair
Department of Infectious Diseases, Aarhus University Hospital
Søren Jensen-Fangel, MD study director
Department of Infectious Diseases, Aarhus University Hospital
Martin Tolstrup, MSc study director
Department of Infectious Diseases, Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Twinrix in people with Hepatitis B, run by University of Aarhus at 1 site in Denmark.
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 3 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 26 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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?
Results are not available in the source record.
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?
Estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization (time frame: within 9. month from 1. vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Oct 2012.