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.

Abstract

BACKGROUND:

Patients on dialysis are hyporesponsive to the hepatitis B virus vaccines (HBVv). We examined intradermal (ID) HBVv Sci-B-Vac, with topical Toll-like receptor 7 (TLR7) agonist imiquimod pretreatment in dialysis patients.

METHODS:

We enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into 1 treatment group, topical imiquimod cream followed by ID HBVv (IMQ + ID); and 2 control groups: topical aqueous cream (placebo) followed by ID HBVv (AQ + ID) or topical aqueous cream followed by intramuscular HBVv (AQ + IM). The primary endpoint was the seroprotection rate (hepatitis B surface antibody ≥10 mIU/mL) at 52 weeks.

RESULTS:

Ninety-four patients were enrolled, among which 57.4% were previous nonresponders. Seroprotection rate was significantly better at week 52 for the IMQ + ID group with 96.9% compared to 74.2% and 48.4% for AQ + ID and AQ + IM groups, respectively (P < .0001). The geometric mean concentration was significantly higher at week 52 for the IMQ + ID group: 1135 (95% confidence interval [CI], 579.4-2218.2) mIU/mL, compared to 86.9 (95% CI, 18.5-409.3) mIU/mL and 7.2 (2.0-26.5) mIU/mL for the AQ + ID and AQ + IM groups, respectively (P < .0001). IMQ + ID vaccination (odds ratio, 3.70 [95% CI, 1.16-11.81]; P = .027) was the only factor independently associated with higher 52-week seroprotection rate. Adverse reaction was infrequent.

CONCLUSIONS:

Pretreatment with topical imiquimod before ID HBVv Sci-B-Vac was safe with favorable seroprotection in dialysis patients.

CLINICAL TRIALS REGISTRATION:

NCT02621112.

• Authors: Ivan Fan-Ngai Hung, Desmond Yat-Hin Yap, Terence Pok-Siu Yip, Ricky Ruiqi Zhang, Kelvin Kai-Wang To, Kwok-Hung Chan, Sydney Chi-Wai Tang, Sing-Leung Lui, Yotam Levin, Efrat Kochba, Johnson Yiu-Nam Lau, Man-Fung Yuen, Tak-Mao Chan, Kwok-Yung Yuen
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 73 Issue 2 Pg. e304-e311 (07 15 2021) ISSN: 1537-6591 [Electronic] United States
• PMID: 32556176 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Hepatitis B Vaccines
• Toll-Like Receptor 7
• Imiquimod

Topics

• Adult
• Hepatitis B
• Hepatitis B Vaccines
• Humans
• Imiquimod
• Injections, Intradermal
• Injections, Intramuscular
• Renal Dialysis
• Toll-Like Receptor 7
• Vaccination