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. 2020 Jun 18;ciaa804. doi: 10.1093/cid/ciaa804. Online ahead of print.

Abstract

Background: Patients on dialysis are hyporesponsive to the current hepatitis B virus vaccines (HBVv). We conducted a phase-2 trial examining four-doses of intradermal (ID) HBVv Sci-B-Vac™, with topical TLR7 agonist imiquimod pretreatment in dialysis patients.

Methods: In this double-blind, randomized-controlled trial, we enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into one treatment: topical imiquimod-cream followed by intradermal HBVv (IMQ_ID), and two control groups: topical aqueous-cream (placebo) followed by ID HBVv (AQ_ID) or topical aqueous-cream followed by intramuscular (IM) HBVv (AQ_IM). The primary end-point was the seroprotection rate (anti-HBs≥10mIU/mL) at 52 weeks after the first dose of HBVv.

Results: Ninety-four patients on dialysis were enrolled, among which 57.4% were previous non-responders. The primary outcome of seroprotection rate was significantly better at week 52 for the treatment group (IMQ_ID) with 96.9% seroprotection rate, comparing compared to 74.2% and 48.4% for the AQ_ID and AQ_IM groups, respectively (p<0.0001). The GMC was also significantly higher at week 52 for the IMQ_ID group of 1135 mIU/mL (95% CI, 579.4-2218.2 mIU/mL), compared to 86.9 mIU/mL (95% CI, 18.5-409.3 mIU/mL) and 7.2 mIU/mL (2.0-26.5mIU/mL) for the AQ_ID and AQ_IM groups, respectively (p<0.0001). IMQ_ID vaccination [OR, 3.70 (95% CI, 1.16-11.81;p=0.027) was the only factor independently associated with higher seroprotection rate at 52 weeks. Adverse reaction was infrequent.

Conclusions: Pretreatment with topical imiquimod (TLR7 agonist) before ID HBVv Sci-B-Vac™ was safe with favorable seroprotection and as such potentially improved prevention against HBV infection in dialysis patients.

Keywords: TLR7 agonist; dialysis; hepatitis B vaccination; intradermal.