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HBV Vaccine in Renal Failure Patients

Primary Purpose

Renal Failure

Status

Completed

Phase

Phase 2

Locations

Hong Kong

Study Type

Interventional

Intervention

Intradermal HBVv with imiquimod

Intradermal HBVv with aqueous cream

Intramuscular HBVv with aqueous cream

About this trial

This is an interventional prevention trial for Renal Failure

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Hong Kong, Queen Mary Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Intradermal HBVv with imiquimod

Intradermal HBVv with aqueous cream

Intramuscular HBVv with aqueous cream

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Seroprotection rate to HBV

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

Secondary Outcome Measures

Adverse reaction to hepatitis B vaccine

Seroprotection rate to HBV

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

GMT fold increase of anti-HBs

Full Information

NCT ID

NCT02621112

First Posted

December 1, 2015

Last Updated

October 21, 2019

Sponsor

The University of Hong Kong

1. Study Identification

Unique Protocol Identification Number

NCT02621112

Brief Title

HBV Vaccine in Renal Failure Patients

Official Title

Efficacy of Intradermal Hepatitis B Vaccine in Renal Failure Patients

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

January 2016 (undefined)

Primary Completion Date

December 2018 (Actual)

Study Completion Date

March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Hong Kong

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Failure

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

94 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intradermal HBVv with imiquimod

Arm Type

Experimental

Arm Description

Arm Title

Intradermal HBVv with aqueous cream

Arm Type

Active Comparator

Arm Description

Arm Title

Intramuscular HBVv with aqueous cream

Arm Type

Active Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Intradermal HBVv with imiquimod

Intervention Description

Intradermal hepatitis B vaccine with imiquimod pretreatment

Intervention Type

Biological

Intervention Name(s)

Intradermal HBVv with aqueous cream

Intervention Description

Intradermal hepatitis B vaccine with aqueous cream pretreatment

Intervention Type

Biological

Intervention Name(s)

Intramuscular HBVv with aqueous cream

Intervention Description

Intramuscular hepatitis B vaccine with aqueous cream pretreatment

Primary Outcome Measure Information:

Title

Seroprotection rate to HBV

Description

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

Time Frame

12 months after first dose of hepatitis B vaccine

Secondary Outcome Measure Information:

Title

Adverse reaction to hepatitis B vaccine

Time Frame

1 month

Title

Seroprotection rate to HBV

Description

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

Time Frame

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

Title

GMT fold increase of anti-HBs

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ivan FN Hung, MD FRCP

Organizational Affiliation

The University of Hong Kong

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Hong Kong, Queen Mary Hospital

City

Hong Kong

Country

Hong Kong

12. IPD Sharing Statement

Citations:

PubMed Identifier

32556176

Citation

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.

Results Reference

derived

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HBV Vaccine in Renal Failure Patients

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