ID HBV Vaccination With Imiquimod in OBI

Overview

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.

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.