ID HBV Vaccination With Imiquimod in OBI

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Biological: Imiquimod + ID HBVv; Biological: Aqueous + ID HBVv; Biological: Imiquimod + IM HBVv

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 Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imiquimod + ID HBVv; topical imiquimod + intradermal hepatitis B vaccination	Biological: Imiquimod + ID HBVv; Imiquimod ointment + intradermal 10μg Sci-B-Vac vaccine
Active Comparator: Aqueous + ID HBVv; topical aqueous + intradermal hepatitis B vaccination	Biological: Aqueous + ID HBVv; Aqueous ointment + intradermal 10μg Sci-B-Vac vaccine
Active Comparator: Imiquimod + IM HBVv; topical imiquimod + intramuscular hepatitis B vaccination	Biological: Imiquimod + IM HBVv; Imiquimod ointment + intramuscular 10μg Sci-B-Vac vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotection rate to HBV at 12 month	Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotection rate to HBV at 1 month	Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL	1 month
Seroprotection rate to HBV at 6 month	Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL	6 month
GMT of anti-HBs at 1 month	Geometric mean titre of anti-HBs antibody at 1 month after vaccination	1 month
GMT of anti-HBs at 6 month	Geometric mean titre of anti-HBs antibody at 6 month after vaccination	6 month
GMT of anti-HBs at 12 month	Geometric mean titre of anti-HBs antibody at 12 month after vaccination	12 month

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: September 27, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (Actual): October 12, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Vaccination
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Imiquimod
• Other Study ID Numbers: UW 15-106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No