HBV Vaccine in Renal Failure Patients

NCT02621112 | Completed Phase 2 DMC

• 1 other identifier: UW 11-209
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatitis B virus infection remains an important clinical issue among patients on renal replacement therapy. Seroconversion rate as defined by an anti-HBs Ab titer \> 10 IU/L after intramuscular hepatitis B vaccination (HBVv) remains poor in this cohort. Factors associated with inadequate anti-HBs response include older age, diabetes mellitus, obesity and low hepatitis B vaccine dose. Various small-scale studies including multiple high dose intramuscular vaccination or multiple small dose intradermal vaccination were attempted with variable response. Recent study on dose sparing seasonal influenza vaccine delivered via a novel intradermal microneedle has demonstrated good immunogenic responses similar to full-dose intramuscular vaccination. Imiquimod, a synthetic TLR7 agonist useful for the treatment of DNA virus infection, has been shown to improve vaccine immunogenicity. The investigators therefore propose a prospective, randomized study to compare the safety and immunogenicity of intradermal hepatitis B vaccination with this novel device with intramuscular in patients on renal replacement therapy.

Conditions

Renal Failure

Outcome Measures

Primary Outcomes (1)

• Seroprotection rate to HBV

  percentage of recruited subjects with anti-HBs \>10 mIU/mL

  12 months after first dose of hepatitis B vaccine

Secondary Outcomes (3)

• Adverse reaction to hepatitis B vaccine

  1 month

• Seroprotection rate to HBV

  1, 3, 6 and 18 months after first dose of hepatitis B vaccine

• GMT fold increase of anti-HBs

  1, 3, 6, 12 and 18 months after first dose of hepatitis B vaccine

Study Arms (3)

Intradermal HBVv with imiquimod

EXPERIMENTAL

Intradermal hepatitis B vaccination with topical imiquimod pretreatment. Subjects to receive intradermal 10mcg of recombinant hepatitis B vaccine at two separate sites (5mcg) with topical imiquimod ointment pretreatment 5 minutes before injection at 0, 1, 3, 6 months

Biological: Intradermal HBVv with imiquimod

Intradermal HBVv with aqueous cream

ACTIVE COMPARATOR

Intradermal hepatitis B vaccination with topical aqueous cream. Subjects to receive intradermal 10mcg of recombinant hepatitis B vaccine at two separate sites (5mcg) with topical aqueous cream pretreatment 5 minutes before injection at 0, 1, 3, 6 months

Biological: Intradermal HBVv with aqueous cream

Intramuscular HBVv with aqueous cream

ACTIVE COMPARATOR

Intramuscular hepatitis B vaccination with topical aqueous cream. Subjects to receive intramuscular 10mcg of recombinant hepatitis B vaccine at two separate sites (5mcg) with topical aqueous cream pretreatment 5 minutes before injection at 0, 1, 3, 6 months

Biological: Intramuscular HBVv with aqueous cream

Interventions

Intradermal HBVv with imiquimod BIOLOGICAL

Intradermal hepatitis B vaccine with imiquimod pretreatment

Intradermal HBVv with imiquimod

Intradermal HBVv with aqueous cream BIOLOGICAL

Intradermal hepatitis B vaccine with aqueous cream pretreatment

Intradermal HBVv with aqueous cream

Intramuscular HBVv with aqueous cream BIOLOGICAL

Intramuscular hepatitis B vaccine with aqueous cream pretreatment

Intramuscular HBVv with aqueous cream

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients recruited have to be aged ≥ 21 years, with history of chronic renal failure and on renal replacement therapy (continuous ambulatory peritoneal dialysis or hemodialysis).
• All patients have to give written informed consent and will have up to 1 week period to decide.
• Subjects must be available to complete the study and comply with study procedures.
• Patients are willing to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response.
• All recruited subjects have to be HBsAg, anti-HBs and anti-HIV negative before recruitment.

You may not qualify if:

• Inability to comprehend and to follow all required study procedures
• History or any illness that might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
• Have a recent history (documented, confirmed or suspected) of a flu-like disease within a week of vaccination.
• Have a known allergy to components of the Study Vaccines.
• Have a positive urine or serum pregnancy test within 24 hours prior to vaccination, or women who are breastfeeding.
• Have an active neoplastic disease or a history of any hematologic malignancy.
• Have known chronic active hepatitis B and hepatitis C (HBsAg+ve and anti-HCV+ve).
• Have known active human immunodeficiency virus (HIV).
• 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.
• Unwilling to refuse participation in another clinical study through the end of this study.
• Axillary temperature ≥ 38°C or oral temperature ≥ 38.5°C within 3 days of intended study vaccination.
• Have a history of alcohol or drug abuse in the last 5 years.
• 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, Queen Mary Hospital

Hong Kong, Hong Kong

Location

Related Publications (1)

• Hung IF, Yap DY, Yip TP, Zhang RR, To KK, Chan KH, Tang SC, Lui SL, Levin Y, Kochba E, Lau JY, Yuen MF, Chan TM, Yuen KY. A Double-blind, Randomized Phase 2 Controlled Trial of Intradermal Hepatitis B Vaccination With a Topical Toll-like Receptor 7 Agonist Imiquimod, in Patients on Dialysis. Clin Infect Dis. 2021 Jul 15;73(2):e304-e311. doi: 10.1093/cid/ciaa804.

  PMID: 32556176 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Ivan FN Hung, MD FRCP

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 3, 2015
• Study Start: January 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: March 1, 2019
• Last Updated: October 22, 2019

Record last verified: 2019-10

Locations

HK (1)