ID HBV Vaccination With Imiquimod in OBI

NCT03307902 | Completed Phase 2 DMC

• 1 other identifier: UW 15-106
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Hepatitis B

Keywords

Vaccination

Outcome Measures

Primary Outcomes (1)

• Seroprotection rate to HBV at 12 month

  Percentage of recruited subjects with anti-HBs antibody titre \>10mIU/mL

  12 month

Secondary Outcomes (5)

• Seroprotection rate to HBV at 1 month

  1 month

• Seroprotection rate to HBV at 6 month

  6 month

• GMT of anti-HBs at 1 month

  1 month

• GMT of anti-HBs at 6 month

  6 month

• GMT of anti-HBs at 12 month

  12 month

Study Arms (3)

Imiquimod + ID HBVv

EXPERIMENTAL

topical imiquimod + intradermal hepatitis B vaccination

Biological: Imiquimod + ID HBVv

Aqueous + ID HBVv

ACTIVE COMPARATOR

topical aqueous + intradermal hepatitis B vaccination

Biological: Aqueous + ID HBVv

Imiquimod + IM HBVv

ACTIVE COMPARATOR

topical imiquimod + intramuscular hepatitis B vaccination

Biological: Imiquimod + IM HBVv

Interventions

Imiquimod + ID HBVv BIOLOGICAL

Imiquimod ointment + intradermal 10μg Sci-B-Vac vaccine

Imiquimod + ID HBVv

Aqueous + ID HBVv BIOLOGICAL

Aqueous ointment + intradermal 10μg Sci-B-Vac vaccine

Aqueous + ID HBVv

Imiquimod + IM HBVv BIOLOGICAL

Imiquimod ointment + intramuscular 10μg Sci-B-Vac vaccine

Imiquimod + IM HBVv

Eligibility Criteria

• Age: 27 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

University of Hong Kong

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 12, 2017
• Study Start: October 1, 2016
• Primary Completion: March 31, 2019
• Study Completion: July 31, 2019
• Last Updated: October 22, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)