HBV Vaccine in Renal Failure Patients

NCT ID: NCT02621112

Last Updated: 2019-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2019-03-31

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.

Detailed Description

The investigators aim to recruit at least 120 subjects on renal replacement therapy in this prospective double blind randomized controlled trial. All recruited subjects have to be HBsAg and anti-HBs negative before recruitment. Subjects were randomly assigned to three groups.

All patients received 4 doses of hepatitis B vaccine at 0,1,3 and 6 months: Group 1: to receive intradermal 10mcg of recombinant hepatitis B vaccine at two separate sites (5mcg) with topical imiquimod ointment pretreatment 5 minutes before injection. Group 2: to receive intradermal 10mcg of recombinant hepatitis B vaccine at two separate sites (5mcg) with topical placebo aqueous cream pretreatment 5 minutes before injection. Group 3: to receive intramuscular 10mcg (1mL) of recombinant hepatitis B vaccine at two separate sites (5mcg) with topical placebo aqueous cream pretreatment 5 minutes before injection.

Subjects will be advised not to wash the topical treatment for 8 hours after vaccination. Patients and investigators will be blinded to the type of topical treatment applied. Anti-HBs titre will be measured at baseline, before each vaccination, and at 12 and 18 months after the first dose of vaccination.

The primary end point is the seroprotection rate of the HBVv at 12 months after the first dose of vaccination. The secondary end points are the seroprotection rate of HBVv and the geometric mean titre (GMT) fold increase of the anti-HBs at 1, 3, 6, 12 (GMT only) and 18 months after the first dose of vaccination. Adverse reactions of the vaccine will also be assessed immediately and for 1 month after vaccination.

Conditions

Renal Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Intradermal HBVv with imiquimod

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

Group Type: EXPERIMENTAL

Intradermal HBVv with imiquimod

Intervention Type: BIOLOGICAL

Intradermal hepatitis B vaccine with imiquimod pretreatment

Intradermal HBVv with aqueous cream

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

Group Type: ACTIVE_COMPARATOR

Intradermal HBVv with aqueous cream

Intervention Type: BIOLOGICAL

Intradermal hepatitis B vaccine with aqueous cream pretreatment

Intramuscular HBVv with aqueous cream

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

Group Type: ACTIVE_COMPARATOR

Intramuscular HBVv with aqueous cream

Intervention Type: BIOLOGICAL

Intramuscular hepatitis B vaccine with aqueous cream pretreatment

Interventions

Intradermal HBVv with imiquimod

Intradermal hepatitis B vaccine with imiquimod pretreatment

Intervention Type: BIOLOGICAL

Intradermal HBVv with aqueous cream

Intradermal hepatitis B vaccine with aqueous cream pretreatment

Intervention Type: BIOLOGICAL

Intramuscular HBVv with aqueous cream

Intramuscular hepatitis B vaccine with aqueous cream pretreatment

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ivan FN Hung, MD FRCP

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

University of Hong Kong, Queen Mary Hospital

Hong Kong, , Hong Kong

Countries

Hong Kong

References

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.

Reference Type: DERIVED

PMID: 32556176 (View on PubMed)

Other Identifiers

UW 11-209

Identifier Type: -

Identifier Source: org_study_id