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HBV Vaccine in Renal Failure Patients

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ClinicalTrials.gov Identifier: NCT02621112
Recruitment Status : Completed
First Posted : December 3, 2015
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
The University of Hong Kong

Tracking Information
First Submitted Date  ICMJE December 1, 2015
First Posted Date  ICMJE December 3, 2015
Last Update Posted Date October 22, 2019
Study Start Date  ICMJE January 2016
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2015)
Seroprotection rate to HBV [ Time Frame: 12 months after first dose of hepatitis B vaccine ]
percentage of recruited subjects with anti-HBs >10 mIU/mL
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2015)
  • Adverse reaction to hepatitis B vaccine [ Time Frame: 1 month ]
  • Seroprotection rate to HBV [ Time Frame: 1, 3, 6 and 18 months after first dose of hepatitis B vaccine ]
    percentage of recruited subjects with anti-HBs >10 mIU/mL
  • GMT fold increase of anti-HBs [ Time Frame: 1, 3, 6, 12 and 18 months after first dose of hepatitis B 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 HBV Vaccine in Renal Failure Patients
Official Title  ICMJE Efficacy of Intradermal Hepatitis B Vaccine in Renal Failure Patients
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Renal Failure
Intervention  ICMJE
  • Biological: Intradermal HBVv with imiquimod
    Intradermal hepatitis B vaccine with imiquimod pretreatment
  • Biological: Intradermal HBVv with aqueous cream
    Intradermal hepatitis B vaccine with aqueous cream pretreatment
  • Biological: Intramuscular HBVv with aqueous cream
    Intramuscular hepatitis B vaccine with aqueous cream pretreatment
Study Arms  ICMJE
  • Experimental: 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
    Intervention: Biological: Intradermal HBVv with imiquimod
  • Active Comparator: 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
    Intervention: Biological: Intradermal HBVv with aqueous cream
  • Active Comparator: 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
    Intervention: Biological: Intramuscular HBVv with aqueous cream
Publications * 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.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2019)
94
Original Estimated Enrollment  ICMJE
 (submitted: December 2, 2015)
120
Actual Study Completion Date  ICMJE March 2019
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hong Kong
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02621112
Other Study ID Numbers  ICMJE UW 11-209
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The University of Hong Kong
Study Sponsor  ICMJE The University of Hong Kong
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ivan FN Hung, MD FRCP The University of Hong Kong
PRS Account The University of Hong Kong
Verification Date October 2019

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