Plain English Summary
Background and study aims
Hepatitis B is a liver infection caused by a virus. The surface antigen is the part of the hepatitis B virus that is found in the blood of someone who is infected. Hepatitis B carriers who no longer have the surface antigen in their blood have a better prognosis. Nevertheless, they are still at risk of developing a flare up of hepatitis B, acute liver failure, cirrhosis (scarring of the liver) and hepatocellular carcinoma (liver cancer). We therefore would like to evaluate the effect and safety of treatment with imiquimod ointment before hepatitis B vaccination in patients who have lost their surface antigens.
Who can participate?
Patients aged 18 or over who have lost their surface antigens during follow-up of chronic hepatitis B infection
What does the study involve?
Participants are randomly allocated to receive either three doses of hepatitis B vaccine or a placebo (dummy) vaccine at 0, 1 and 6 months. Participants are also randomly allocated into three groups. Group 1 is treated with an imiquimod ointment before intradermal vaccination (into the skin). Group 2 is treated with an imiquimod ointment before intramuscular vaccination (into the muscle). Group 3 is treated with a cream before intradermal vaccination (into the skin).
What are the possible benefits and risks of participating?
The potential benefit is that the participants may be cured of their hepatitis B carrier status and successfully mount an antibody response against hepatitis B. The risks are local side effects of pain and swelling over the vaccination site. Patients who do not receive the vaccine might not be able to mount an immune response against hepatitis B.
Where is the study run from?
Queen Mary Hospital (Hong Kong)
When is the study starting and how long is it expected to run for?
April 2016 to March 2018
Who is funding the study?
University of Hong Kong
Who is the main contact?
Prof Ivan Hung
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
UW 15-106
Study information
Scientific title
A double-blind randomized controlled trial of hepatitis B vaccination with topical imiquimod in subjects with occult hepatitis B
Acronym
Study hypothesis
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 occult hepatitis B (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.
Ethics approval
Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB), 11/03/2015, IRB Reference Number: UW 15-106
Study design
Double-blind randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Patients with occult hepatitis B (OBI) as defined by chronic hepatitis B carrier, with documented loss of HBsAg, negative anti-HBs, positive anti-HBc and negative HBV DNA.
Intervention
Recruited patients will be randomised into 3 groups in the ratio of 1:1:1. Each patient will receive a 3-dose Sci-B-Vac™ regime or placebo 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 intramuscular HBsAg each time with topical imiquimod ointment pretreatment; Group 3 will receive a total of 10μg intradermal HBsAg each time with topical aqueous cream pretreatment.
Intervention type
Biological/Vaccine
Phase
Drug names
Primary outcome measure
Percentage of patients with anti-HBs antibody titre ≥10 IU/L at 12 months
Secondary outcome measures
1. Seroconversion and seroprotection rate at 1, 6 and 12 months after the first first dose of vaccination
2. The GMT fold increase at 1, 6 and 12 months
3. Safety and side effects after vaccination
Overall trial start date
30/04/2016
Overall trial end date
31/03/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Subjects recruited have to be aged ≥18 years with no history of previous hepatitis B vaccination, with documentation of loss of HBsAg without anti-HBs production during follow-up of the chronic hepatitis B infection, with normal liver function tests and negative HBV DNA
2. Subjects have to give written informed consent
3. Subjects must be available to complete the study and comply with study procedures
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Participant exclusion criteria
1. 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
2. Subjects have a recent history (documented, confirmed or suspected) of a flu-like disease within a week of vaccination
3. Subjects have a known allergy to components of the study vaccine Sci-B-Vac™
4. Subjects have a positive urine or serum pregnancy test within 24 hours prior to vaccination, or women who are breastfeeding
5. Subjects have an active neoplastic disease or a history of any hematologic malignancy
6. Subjects have known chronic active hepatitis C (anti-HCV+ve), autoimmune hepatitis or cirrhosis
7. Subjects have known active human immunodeficiency virus infection (anti-HIV+ve)
8. 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
9. Subjects participate in another clinical study during the current study
10. Subjects have axillary temperature ≥38°C or oral temperature ≥38.5°C within 3 days of intended study vaccination
11. Subjects have a history of alcohol or drug abuse in the last 5 years
12. Subjects have any condition that the investigator believes may interfere with successful completion of the study
Recruitment start date
30/04/2016
Recruitment end date
31/03/2017
Locations
Countries of recruitment
Hong Kong
Trial participating centre
Queen Mary Hospital
102 Pokfulam Road
Hong Kong
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Hong Kong
Funders
Funder type
University/education
Funder name
University of Hong Kong
Alternative name(s)
HKU
Funding Body Type
government organisation
Funding Body Subtype
government non-federal
Location
Hong Kong
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
31/03/2019
Participant level data
Stored in repository
Basic results (scientific)
Publication list