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

NCT04083157 | Completed Phase 2

• 1 other identifier: IBDHepBVaccine
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammatory Bowel Diseases; Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Sero-protection rate to HBV

  Percentage of recruited subjects with anti-HBs titre ≥ 10 IU/L

  12 months after first dose of vaccine

Secondary Outcomes (5)

• Injection site adverse effect of intradermal hepatitis B vaccine in IBD patients

  up to 7 days after each dose of vaccination

• Systemic adverse effect of intradermal hepatitis B vaccine in IBD patients

  up to 7 days after each dose of vaccination

• Sero-protection rate to HBV at 1 and 6 months after dose of vaccine

  1 and 6 month after first dose of vaccine

• Percentage of good responder defined as anti-HBs ≥ 100 IU/L

  12 month after first dose of vaccine

• Geometric mean concentration of anti-HBs at 1, 6 and 12 months after first dose of vaccine

  1, 6 and 12 month after first dose of vaccine

Study Arms (2)

Intradermal hepatitis B vaccine with imiquimod

EXPERIMENTAL

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.

Biological: Intradermal hepatitis B vaccine with imiquimod

Intramuscular hepatitis B vaccine with aqueous cream

ACTIVE COMPARATOR

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.

Biological: Intramuscular hepatitis B vaccine with aqueous cream

Interventions

Intradermal hepatitis B vaccine with imiquimod BIOLOGICAL

Intradermal hepatitis B vaccine with topical imiquimod pretreatment

Intradermal hepatitis B vaccine with imiquimod

Intramuscular hepatitis B vaccine with aqueous cream BIOLOGICAL

Intramuscular hepatitis B vaccine with topical aqueous cream pretreatment

Intramuscular hepatitis B vaccine with aqueous cream

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Queen Mary Hospital

Hong Kong, China

Location

Related Publications (1)

• Ko KL, Lam YF, Cheung KS, Hung IF, Leung WK. Clinical trial: intra dermal hepatitis B vaccination with topical imiquimod versus intra muscular hepatitis B vaccination in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2022 Jul;56(2):301-309. doi: 10.1111/apt.16970. Epub 2022 May 11.

  PMID: 35546255 DERIVED

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Hepatitis B

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Wai Keung Leung, MD

  The University of Hong Kong

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2019
• First Posted: September 10, 2019
• Study Start: August 12, 2019
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2021
• Last Updated: May 18, 2022

Record last verified: 2022-05

Locations

CN (1)