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ID HBV Vaccination With Imiquimod in OBI

Primary Purpose

Hepatitis B

Status

Completed

Phase

Phase 2

Locations

Hong Kong

Study Type

Interventional

Intervention

Imiquimod + ID HBVv

Aqueous + ID HBVv

Imiquimod + IM HBVv

About this trial

This is an interventional prevention trial for Hepatitis B focused on measuring Vaccination

Eligibility Criteria

27 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Hong Kong

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Imiquimod + ID HBVv

Aqueous + ID HBVv

Imiquimod + IM HBVv

Arm Description

topical imiquimod + intradermal hepatitis B vaccination

topical aqueous + intradermal hepatitis B vaccination

topical imiquimod + intramuscular hepatitis B vaccination

Outcomes

Primary Outcome Measures

Seroprotection rate to HBV at 12 month

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

Secondary Outcome Measures

Seroprotection rate to HBV at 1 month

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

Seroprotection rate to HBV at 6 month

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

GMT of anti-HBs at 1 month

Geometric mean titre of anti-HBs antibody at 1 month after vaccination

GMT of anti-HBs at 6 month

Geometric mean titre of anti-HBs antibody at 6 month after vaccination

GMT of anti-HBs at 12 month

Geometric mean titre of anti-HBs antibody at 12 month after vaccination

Full Information

NCT ID

NCT03307902

First Posted

September 27, 2017

Last Updated

October 21, 2019

Sponsor

The University of Hong Kong

1. Study Identification

Unique Protocol Identification Number

NCT03307902

Brief Title

ID HBV Vaccination With Imiquimod in OBI

Official Title

Intradermal Hepatitis B Vaccination With Imiquimod in Occult Hepatitis B Infection

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

October 1, 2016 (Actual)

Primary Completion Date

March 31, 2019 (Actual)

Study Completion Date

July 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B

Keywords

Vaccination

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Double blind

Allocation

Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Imiquimod + ID HBVv

Arm Type

Experimental

Arm Description

topical imiquimod + intradermal hepatitis B vaccination

Arm Title

Aqueous + ID HBVv

Arm Type

Active Comparator

Arm Description

topical aqueous + intradermal hepatitis B vaccination

Arm Title

Imiquimod + IM HBVv

Arm Type

Active Comparator

Arm Description

topical imiquimod + intramuscular hepatitis B vaccination

Intervention Type

Biological

Intervention Name(s)

Imiquimod + ID HBVv

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Aqueous + ID HBVv

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Imiquimod + IM HBVv

Intervention Description

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

Primary Outcome Measure Information:

Title

Seroprotection rate to HBV at 12 month

Description

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

Time Frame

12 month

Secondary Outcome Measure Information:

Title

Seroprotection rate to HBV at 1 month

Description

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

Time Frame

1 month

Title

Seroprotection rate to HBV at 6 month

Description

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

Time Frame

6 month

Title

GMT of anti-HBs at 1 month

Description

Geometric mean titre of anti-HBs antibody at 1 month after vaccination

Time Frame

1 month

Title

GMT of anti-HBs at 6 month

Description

Geometric mean titre of anti-HBs antibody at 6 month after vaccination

Time Frame

6 month

Title

GMT of anti-HBs at 12 month

Description

Geometric mean titre of anti-HBs antibody at 12 month after vaccination

Time Frame

12 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

27 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

University of Hong Kong

City

Hong Kong

Country

Hong Kong

12. IPD Sharing Statement

Plan to Share IPD

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ID HBV Vaccination With Imiquimod in OBI

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