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ID HBV Vaccination With Imiquimod in OBI

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ClinicalTrials.gov Identifier: NCT03307902
Recruitment Status : Completed
First Posted : October 12, 2017
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
The University of Hong Kong

Tracking Information
First Submitted Date  ICMJE September 27, 2017
First Posted Date  ICMJE October 12, 2017
Last Update Posted Date October 22, 2019
Actual Study Start Date  ICMJE October 1, 2016
Actual Primary Completion Date March 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 10, 2017)
Seroprotection rate to HBV at 12 month [ Time Frame: 12 month ]
Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2017)
  • Seroprotection rate to HBV at 1 month [ Time Frame: 1 month ]
    Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
  • Seroprotection rate to HBV at 6 month [ Time Frame: 6 month ]
    Percentage of recruited subjects with anti-HBs antibody titre >10mIU/mL
  • GMT of anti-HBs at 1 month [ Time Frame: 1 month ]
    Geometric mean titre of anti-HBs antibody at 1 month after vaccination
  • GMT of anti-HBs at 6 month [ Time Frame: 6 month ]
    Geometric mean titre of anti-HBs antibody at 6 month after vaccination
  • GMT of anti-HBs at 12 month [ Time Frame: 12 month ]
    Geometric mean titre of anti-HBs antibody at 12 month after vaccination
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ID HBV Vaccination With Imiquimod in OBI
Official Title  ICMJE Intradermal Hepatitis B Vaccination With Imiquimod in Occult Hepatitis B Infection
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Double blind
Primary Purpose: Prevention
Condition  ICMJE Hepatitis B
Intervention  ICMJE
  • Biological: Imiquimod + ID HBVv
    Imiquimod ointment + intradermal 10μg Sci-B-Vac vaccine
  • Biological: Aqueous + ID HBVv
    Aqueous ointment + intradermal 10μg Sci-B-Vac vaccine
  • Biological: Imiquimod + IM HBVv
    Imiquimod ointment + intramuscular 10μg Sci-B-Vac vaccine
Study Arms  ICMJE
  • Experimental: Imiquimod + ID HBVv
    topical imiquimod + intradermal hepatitis B vaccination
    Intervention: Biological: Imiquimod + ID HBVv
  • Active Comparator: Aqueous + ID HBVv
    topical aqueous + intradermal hepatitis B vaccination
    Intervention: Biological: Aqueous + ID HBVv
  • Active Comparator: Imiquimod + IM HBVv
    topical imiquimod + intramuscular hepatitis B vaccination
    Intervention: Biological: Imiquimod + IM HBVv
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2019)
120
Original Estimated Enrollment  ICMJE
 (submitted: October 10, 2017)
70
Actual Study Completion Date  ICMJE July 31, 2019
Actual Primary Completion Date March 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 27 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hong Kong
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03307902
Other Study ID Numbers  ICMJE UW 15-106
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party The University of Hong Kong
Study Sponsor  ICMJE The University of Hong Kong
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account The University of Hong Kong
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP