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Intra-dermal With Topical Imiquimod Pretreatment Versus Intra-muscular Hepatitis B Vaccination in IBD Patients

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ClinicalTrials.gov Identifier: NCT04083157
Recruitment Status : Recruiting
First Posted : September 10, 2019
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
The University of Hong Kong

Tracking Information
First Submitted Date  ICMJE September 2, 2019
First Posted Date  ICMJE September 10, 2019
Last Update Posted Date September 10, 2019
Actual Study Start Date  ICMJE August 12, 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 5, 2019)
Sero-protection rate to HBV [ Time Frame: 12 months after first dose of vaccine ]
Percentage of recruited subjects with anti-HBs titre ≥ 10 IU/L
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2019)
  • Injection site adverse effect of intradermal hepatitis B vaccine in IBD patients [ Time Frame: up to 7 days after each dose of vaccination ]
    Injection site adverse effect recorded as following, with left and right arm recorded separately: Pain - 0 = no pain / 1 = pain on touch / 2 = pain during arm raising / 3 = pain on arm movement Presence or absence of the following Itching Swelling Hot sensation Bruise
  • Systemic adverse effect of intradermal hepatitis B vaccine in IBD patients [ Time Frame: up to 7 days after each dose of vaccination ]
    Presence of absence of systemic adverse effect recorded as following: Fever Malaise Headache Myalgia Arthralgia Nausea Diarrhoea
  • Sero-protection rate to HBV at 1 and 6 months after dose of vaccine [ Time Frame: 1 and 6 month after first dose of vaccine ]
  • Percentage of good responder defined as anti-HBs ≥ 100 IU/L [ Time Frame: 12 month after first dose of vaccine ]
  • Geometric mean concentration of anti-HBs at 1, 6 and 12 months after first dose of vaccine [ Time Frame: 1, 6 and 12 month after first dose of vaccine ]
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 Intra-dermal With Topical Imiquimod Pretreatment Versus Intra-muscular Hepatitis B Vaccination in IBD Patients
Official Title  ICMJE Intra-dermal With Topical Imiquimod Pretreatment Versus Intra-muscular Hepatitis B Vaccination in IBD Patients - a Double-blind Randomized Controlled Trial
Brief Summary

Inflammatory bowel disease (IBD) has witnessed a rising incidence globally and in Hong Kong, an area where chronic hepatitis B (CHB) remains endemic. IBD patients are usually immunocompromised due to the disease itself and secondary to the use of medications including immunosuppressants and biologics, predisposing them to various opportunistic infection including hepatitis. Vaccination against hepatitis B virus (HBV) is recommended to prevent CHB and its related complications including flare up of acute hepatitis, cirrhosis and hepatocellular carcinoma. However, it is reported that efficacy with conventional intramuscular hepatitis B vaccination in IBD patients is suboptimal, especially among those receiving biologic therapies. Various strategies in boosting vaccine immunogenicity including the utilization of higher vaccination dose, shorter dosing interval, or alternate route of vaccine administration have been studied.6

Intradermal route of vaccination has been recently shown to be an effective way in augmenting immune response in specific patient groups who are known poor responders, including elderly and immunocompromised patients. In addition, topical imiquimod, a synthetic agonist of toll-like receptor 7 (TLR7), has been shown to further boost up the immunogenicity response when applied to the site before intradermal vaccination. The proposed study is the first clinical trial comparing the efficacy of intradermal hepatitis B vaccination with adjuvant topical application of imiquimod cream with the conventional intramuscular hepatitis B vaccination in IBD patients.

Detailed Description

Aim of study To compare the efficacy of intradermal hepatitis B vaccination with adjuvant topical imiquimod with conventional intramuscular hepatitis B vaccination in IBD patients.

Methodology Patient recruitment IBD patients newly referred to or currently followed up at Department of Medicine, Queen Mary Hospital will be screened for CHB status (HBsAg/Anti-HBs/Anti-HBc). Patients without CHB infection and evidence of prior HBV vaccination i.e. HBsAg -ve /Anti-HBc-ve/ Anti-HBs -ve will be recruited into the study. Eligible patients will be randomized to receive either intradermal vaccination with Engerix B with topical imiquimod or intramuscular vaccination with Engerix-B with topical aqueous cream as the control arm.

Randomization Eligible patients will be randomized in 1:1 ratio to receive intradermal hepatitis B vaccination (Engerix B) with topical imiquimod cream (as the study arm) or intramuscular hepatitis B vaccination (Engerix-B) with topical aqueous cream (as the control arm). Computer generated random number is used for randomization. Randomization sequences will be kept in opaque envelope and kept by a research staff not directly involved in this study. Once the patient has consented to the study, that research staff will open the envelope and notified the study nurse only of the vaccine allocation. In case of medical emergency or severe adverse reaction to the study medication, unblinding can be performed after notification of the principal investigator who will break the randomization code by revealing the randomization sequence assigned to the concerned study subject.

Vaccine administration Vaccination schedule is identical between the two arms with 3 doses given at 0, 1, 6 month. Participants in the study arm will receive 20 mcg intradermal Engerix-B at two separate sites (10 mcg/0.5 ml) with topical imiquimod ointment pre-treatment 5 minutes before injection. Participants in the control arm will receive 20 mcg intramuscular Engerix-B at two separate sites (10 mcg/ 0.5 ml) with topical placebo aqueous cream pretreatment 5 minutes before injection. The topical treatment will be given in a 4x4cm2 marked at the deltoid on each arm. Vaccination will be administered at clinic by dedicated study nurse, who is not involved in subsequent management of the participants. Both the investigators and the participants will be blinded to the result of randomization as only the study nurse know the route of administration.

Follow up Follow up visits will be arranged at 1,6,12 month after first dose of vaccine. Blood will be taken during each follow up visits for anti-HBs titres.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Inflammatory Bowel Diseases
  • Hepatitis B
Intervention  ICMJE
  • Biological: Intradermal hepatitis B vaccine with imiquimod
    Intradermal hepatitis B vaccine with topical imiquimod pretreatment
  • Biological: Intramuscular hepatitis B vaccine with aqueous cream
    Intramuscular hepatitis B vaccine with topical aqueous cream pretreatment
Study Arms  ICMJE
  • Experimental: Intradermal hepatitis B vaccine with imiquimod
    Subjects in the study arm will receive 20 mcg intradermal Engerix-B at two separate sites (10 mcg/0.5 ml) with topical imiquimod ointment pre-treatment 5 minutes before injection.
    Intervention: Biological: Intradermal hepatitis B vaccine with imiquimod
  • Active Comparator: Intramuscular hepatitis B vaccine with aqueous cream
    Subjects in the control arm will receive 20 mcg intramuscular Engerix-B at two separate sites (10 mcg/ 0.5 ml) with topical placebo aqueous cream pretreatment 5 minutes before injection.
    Intervention: Biological: Intramuscular hepatitis B vaccine with aqueous cream
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 5, 2019)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults aged over 18 years old
  • Confirmed IBD diagnosis (Ulcerative colitis, Crohns disease or IBD-Unclassified)
  • HBsAg -ve / anti-HBs / antiHBc -ve
  • Subjects must give written informed consent
  • Subjects must be available to complete the study and comply with study procedures

Exclusion Criteria:

  • Inability or unwilling to follow all required study procedures
  • History of allergy or severe adverse reaction to the study vaccines, their components, topical imiquimod or aqueous cream
  • Pregnant or lactating women
  • HBsAg / anti-HBs / anti-HBc +ve
  • Confirmed hepatitis C virus (HCV) (anti-HCV +ve) infection
  • Fever (axillary temperature ≥ 38°C or oral temperature ≥ 38.5°C within 3 days of intended study vaccination, subjects can be recruited after the febrile episode subsides
  • Have an active neoplastic disease
  • Have any condition which the investigator believes may prevent successful completion of the study or interfere with results of the study
  • Received an experimental agent (vaccine, drug, biologic, medication) within 1 month prior to vaccination or expect to receive an experimental agent during the study period
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wai Keung Leung, MD 85222553750 waikleung@hku.hk
Contact: Kwan Lung Ko, MBBS 85222553111 kkl516@ha.org.hk
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04083157
Other Study ID Numbers  ICMJE IBDHepBVaccine
Has Data Monitoring Committee Not Provided
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: Undecided
Responsible Party The University of Hong Kong
Study Sponsor  ICMJE The University of Hong Kong
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Wai Keung Leung, MD The University of Hong Kong
PRS Account The University of Hong Kong
Verification Date September 2019

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