Hepatitis BPhase 2/3NCT03307902
ID HBV Vaccination With Imiquimod in OBI
A Phase 2/3 study testing Imiquimod + ID HBVv, Aqueous + ID HBVv and Imiquimod + IM HBVv in people with Hepatitis B, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
During the course of chronic hepatitis B infection, patients may undergo hepatitis B surface antigen (HBsAg) seroclearance, resulting in undetectable circulating HBsAg. With the advance of sensitive nucleic acid detection techniques, HBsAg-negative subjects with detectable HBV DNA in sera or liver tissues can be… Read more about this study
- Who is it for?
- Ages 27 years and older
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Imiquimod + ID HBVv, Aqueous + ID HBVv and Imiquimod + IM HBVv
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Oct 2016to 31 Jul 2019
- Phase
- Phase 2/3
- 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 27 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects recruited have to be aged ≥27 years (born before the universal hepatitis B immunization program for newborns introduced in Hong Kong in 1988), with documentation of loss of HBsAg without anti-HBs production during follow-up of the chronic hepatitis B infection in our clinics in Queen Mary Hospital. These patients should have normal liver function tests.
- Subjects have to give written informed consent.
- Subjects must be available to complete the study and comply with study procedures.
- Subjects are willing to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response.
Who cannot join
- Subjects with a history or any illness that might interfere with the results of the study or participation in the study may pose additional risk to the subjects.
- Subjects have a recent history (documented, confirmed or suspected) of a flu-like disease within a week of vaccination.
- Subjects have a known allergy to components of the study vaccine Sci-B-Vac™.
- Subjects have a positive urine or serum pregnancy test within 24 hours prior to vaccination, or women who are breastfeeding.
- Subjects have an active neoplastic disease or a history of any hematologic malignancy.
- Subjects have known chronic active hepatitis C (anti-HCV+ve), autoimmune hepatitis or cirrhosis.
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- Subjects have known active human immunodeficiency virus infection (anti-HIV+ve).
- Subjects have known chronic liver disease due to primary biliary cirrhosis, metabolic or hereditary causes.
- Subjects have received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study or expect to receive an experimental agent during this study.
- Subjects participate in another clinical study during the current study.
- Subjects have axillary temperature ≥38°C or oral temperature ≥38.5°C within 3 days of intended study vaccination
- Subjects have a history of alcohol or drug abuse in the last 5 years.
- Subjects have any condition that the investigator believes may interfere with successful completion of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intradermal Hepatitis B Vaccination With Imiquimod in Occult Hepatitis B Infection
During the course of chronic hepatitis B infection, patients may undergo hepatitis B surface antigen (HBsAg) seroclearance, resulting in undetectable circulating HBsAg. With the advance of sensitive nucleic acid detection techniques, HBsAg-negative subjects with detectable HBV DNA in sera or liver tissues can be identified. Patients who have undetectable HBsAg and yet detectable HBV DNA in sera or liver tissues are defined as having occult HBV infection (OBI). OBI as a cause of liver disease in HBsAg-negative patients remains clinically important [1,2]. Studies conducted by our research group had demonstrated that patients with HBsAg seroclearance could still develop flare of hepatitis B, advanced liver diseases and HCC [3-6]. Prevention of these complications in OBI patients by conventional intramuscular hepatitis B vaccination (HBVv) remains elusive with poor amnestic anti-HBs response [7].
The objective of this prospective double-blind randomized controlled trial is to evaluate the effect and safety of topical treatment with imiquimod immediately before intradermal vaccination with Sci-B-Vac™ in patients with OBI. Our a priori hypothesis is that imiquimod pretreatment would improve immune responses to Sci-B-Vac™ further in OBI patients, resulting in HBsAb conversion. Thereby preventing subsequent complications including flare of hepatitis, cirrhosis and HCC in these patients.
Read the detailed description
This randomized double-blind placebo-controlled trial will compare the safety, immunogenicity and clinical efficacy of Sci-B-Vac™ with topical ointment pretreatment among 5 groups. Group 1: Intradermal Sci-B-Vac™ with topical imiquimod ointment pretreatment; Group 2: Intradermal Sci-B-Vac™ with topical aqueous cream (placebo) pretreatment; Group 3: Intramuscular Sci-B-Vac™ with topical imiquimod ointment pretreatment.
Vaccination Regimen and Data Collection Enrolled patients will be randomized into 3 groups after written informed consent. Each patient will receive a 3 doses Sci-B-Vac™ regime at 0, 1 and 6 months. Group 1 will receive a total of 10μg intradermal HBsAg each time with topical imiquimod ointment pretreatment; Group 2 will receive a total of 10μg intradermal HBsAg each time with topical aqueous cream pretreatment. Group 3 will receive a total of 10μg intramuscular HBsAg each time with topical imiquimod ointment pretreatment.
The primary outcome measurement will be the seroprotection rate of the HBVv at 12 months after the first dose of vaccination and the secondary outcome measurements will include the seroconversion rate, the GMT fold increase and the safety of the intradermal Sci-B-Vac™ with topical imiquimod treatment at other time points.
- Conditions
- Hepatitis B
- Being tested
- Imiquimod + ID HBVv, Aqueous + ID HBVv, Imiquimod + IM HBVv
- Keywords
- Vaccination
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imiquimod + ID HBVvBiological
Imiquimod ointment + intradermal 10μg Sci-B-Vac vaccine
Aqueous + ID HBVvBiological
Aqueous ointment + intradermal 10μg Sci-B-Vac vaccine
Imiquimod + IM HBVvBiological
Imiquimod ointment + intramuscular 10μg Sci-B-Vac vaccine
| Study group | Role | What they receive |
|---|---|---|
| Imiquimod + ID HBVv | Experimental | topical imiquimod + intradermal hepatitis B vaccination Receives: Biological: Imiquimod + ID HBVv |
| Aqueous + ID HBVv | Active comparator | topical aqueous + intradermal hepatitis B vaccination Receives: Biological: Aqueous + ID HBVv |
| Imiquimod + IM HBVv | Active comparator | topical imiquimod + intramuscular hepatitis B vaccination Receives: Biological: Imiquimod + IM HBVv |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seroprotection rate to HBV at 12 month
Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
Measured: 12 month
Secondary outcomes (5)
Seroprotection rate to HBV at 1 month
Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
Measured: 1 month
Seroprotection rate to HBV at 6 month
Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
Measured: 6 month
GMT of anti-HBs at 1 month
Geometric mean titre of anti-HBs antibody at 1 month after vaccination
Measured: 1 month
GMT of anti-HBs at 6 month
Geometric mean titre of anti-HBs antibody at 6 month after vaccination
Measured: 6 month
GMT of anti-HBs at 12 month
Geometric mean titre of anti-HBs antibody at 12 month after vaccination
Measured: 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2017
- Study start1 Oct 2016
- Primary completion31 Mar 2019
- Study completion31 Jul 2019
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 The University of Hong KongThe 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03307902
- Sponsor's protocol ID
- UW 15-106
- Status last verified
- Oct 2019
- First submitted
- 27 Sep 2017
- Last updated
- 22 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intradermal Hepatitis B Vaccination With Imiquimod in Occult Hepatitis B Infection
- ClinicalTrials.gov ID
- NCT03307902
- Acronym / sponsor ID
- UW 15-106
- Conditions
- Hepatitis B
- Keywords
- Vaccination
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Oct 2016 (actual)
- Primary completion
- 31 Mar 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 12 Oct 2017 (actual)
- 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.
During the course of chronic hepatitis B infection, patients may undergo hepatitis B surface antigen (HBsAg) seroclearance, resulting in undetectable circulating HBsAg. With the advance of sensitive nucleic acid detection techniques, HBsAg-negative subjects with detectable HBV DNA in sera or liver tissues can be identified. Patients who have undetectable HBsAg and yet detectable HBV DNA in sera or liver tissues are defined as having occult HBV infection (OBI). OBI as a cause of liver disease in HBsAg-negative patients remains clinically important [1,2]. Studies conducted by our research group had demonstrated that patients with HBsAg seroclearance could still develop flare of hepatitis B, advanced liver diseases and HCC [3-6]. Prevention of these complications in OBI patients by conventional intramuscular hepatitis B vaccination (HBVv) remains elusive with poor amnestic anti-HBs response [7].
The objective of this prospective double-blind randomized controlled trial is to evaluate the effect and safety of topical treatment with imiquimod immediately before intradermal vaccination with Sci-B-Vac™ in patients with OBI. Our a priori hypothesis is that imiquimod pretreatment would improve immune responses to Sci-B-Vac™ further in OBI patients, resulting in HBsAb conversion. Thereby preventing subsequent complications including flare of hepatitis, cirrhosis and HCC in these patients.
Detailed description
This randomized double-blind placebo-controlled trial will compare the safety, immunogenicity and clinical efficacy of Sci-B-Vac™ with topical ointment pretreatment among 5 groups. Group 1: Intradermal Sci-B-Vac™ with topical imiquimod ointment pretreatment; Group 2: Intradermal Sci-B-Vac™ with topical aqueous cream (placebo) pretreatment; Group 3: Intramuscular Sci-B-Vac™ with topical imiquimod ointment pretreatment.
Vaccination Regimen and Data Collection Enrolled patients will be randomized into 3 groups after written informed consent. Each patient will receive a 3 doses Sci-B-Vac™ regime at 0, 1 and 6 months. Group 1 will receive a total of 10μg intradermal HBsAg each time with topical imiquimod ointment pretreatment; Group 2 will receive a total of 10μg intradermal HBsAg each time with topical aqueous cream pretreatment. Group 3 will receive a total of 10μg intramuscular HBsAg each time with topical imiquimod ointment pretreatment.
The primary outcome measurement will be the seroprotection rate of the HBVv at 12 months after the first dose of vaccination and the secondary outcome measurements will include the seroconversion rate, the GMT fold increase and the safety of the intradermal Sci-B-Vac™ with topical imiquimod treatment at other time points.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Imiquimod + ID HBVv | Experimental | Biological: Imiquimod + ID HBVvtopical imiquimod + intradermal hepatitis B vaccination |
| Aqueous + ID HBVv | Active comparator | Biological: Aqueous + ID HBVvtopical aqueous + intradermal hepatitis B vaccination |
| Imiquimod + IM HBVv | Active comparator | Biological: Imiquimod + IM HBVvtopical imiquimod + intramuscular hepatitis B vaccination |
Who may qualify
- Ages
- 27 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subjects recruited have to be aged ≥27 years (born before the universal hepatitis B immunization program for newborns introduced in Hong Kong in 1988), with documentation of loss of HBsAg without anti-HBs production during follow-up of the chronic hepatitis B infection in our clinics in Queen Mary Hospital. These patients should have normal liver function tests.
- Subjects have to give written informed consent.
- Subjects must be available to complete the study and comply with study procedures.
- Subjects are willing to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response.
Key exclusion criteria (13 listed)
- Subjects with a history or any illness that might interfere with the results of the study or participation in the study may pose additional risk to the subjects.
- Subjects have a recent history (documented, confirmed or suspected) of a flu-like disease within a week of vaccination.
- Subjects have a known allergy to components of the study vaccine Sci-B-Vac™.
- Subjects have a positive urine or serum pregnancy test within 24 hours prior to vaccination, or women who are breastfeeding.
- Subjects have an active neoplastic disease or a history of any hematologic malignancy.
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 |
|---|---|---|
| Imiquimod + ID HBVvImiquimod ointment + intradermal 10μg Sci-B-Vac vaccine | Biological | Imiquimod + ID HBVv |
| Aqueous + ID HBVvAqueous ointment + intradermal 10μg Sci-B-Vac vaccine | Biological | Aqueous + ID HBVv |
| Imiquimod + IM HBVvImiquimod ointment + intramuscular 10μg Sci-B-Vac vaccine | Biological | Imiquimod + IM HBVv |
Primary outcome
Seroprotection rate to HBV at 12 month
Time frame: 12 month
Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
5 secondary outcomes
Seroprotection rate to HBV at 1 month
Time frame: 1 month
Seroprotection rate to HBV at 6 month
Time frame: 6 month
GMT of anti-HBs at 1 month
Time frame: 1 month
GMT of anti-HBs at 6 month
Time frame: 6 month
GMT of anti-HBs at 12 month
Time frame: 12 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Imiquimod + ID HBVv, Aqueous + ID HBVv and Imiquimod + IM HBVv in people with Hepatitis B, run by The University of Hong Kong at 1 site in Hong Kong.
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 4 inclusion and 13 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 22 Oct 2019. 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 Hong Kong. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Seroprotection rate to HBV at 12 month (time frame: 12 month). 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 22 Oct 2019.