title: Immunogenicity and safety of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease.
abstract: BACKGROUND
  Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and patients with chronic kidney disease (CKD) are commonly hyporesponsive to HBV vaccines. Current recommendations for CKD patients are to utilize 4 double-doses (2×20 mcg HBsAg) of a licensed hepatitis B vaccine (HBsAg-Eng).
  
  
  METHODS
  An observer-blind, randomized, active-controlled, parallel group, multicenter trial was conducted among 521 patients 18-75 years of age with CKD, comparing 3 single doses of an investigational hepatitis B vaccine (20 mcg rHBsAg+3000 mcg 1018, a toll-like receptor 9 agonist) given at 0, 4, and 24 weeks to 4 double-doses of HBsAg-Eng (2×20 mcg rHBsAg+500 mcg alum) given at 0, 4, 8, and 24 weeks (total of 8 injections). Participants were followed for 1 year.
  
  
  RESULTS
  Among 467 participants in the modified intent-to-treat population, at the primary endpoint at week 28, the seroprotection rate (SPR: % with anti-HBs≥10mIU/mL) in the HBsAg-1018 group (89.9%) met criteria for noninferiority and superiority to the SPR in the HBsAg-Eng group (81.8%). At week 28, the percentage of participants with anti-HBs≥100mIU/mL in the HBsAg-1018 group (73.6%) was significantly higher than in the HBsAg-Eng group (63.2%). In addition, the geometric mean concentration of anti-HBs in the HBsAg-1018 group (587.1mIU/mL) was significantly higher than in the HBsAg-Eng group (156.5mIU/mL). At weeks 8 and 12 after the first study injection, SPRs in the HBsAg-1018 group were significantly higher than in the HBsAg-Eng group. At 52 weeks, the immune response to HBsAg-1018 remained higher than to HBsAg-Eng. HBsAg-1018 was generally well tolerated and had a similar safety profile to HBsAg-Eng.
  
  
  CONCLUSIONS
  In CKD patients, 3 doses of HBsAg-1018 induced significantly higher seroprotection, earlier seroprotection, and more durable seroprotection than 4 double doses of HBsAg-Eng.
authors.affiliation: Dynavax Technologies, Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710-2753, United States. Electronic address: rjanssen@dynavax.com.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Janssen
authors.forename: Roberto
authors.initials: R
authors.lastname: Mangoo-Karim
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Pergola
authors.forename: Matthias
authors.initials: M
authors.lastname: Girndt
authors.forename: Hamid
authors.initials: H
authors.lastname: Namini
authors.forename: Sophia
authors.initials: S
authors.lastname: Rahman
authors.forename: Sean R
authors.initials: SR
authors.lastname: Bennett
authors.forename: William L
authors.initials: WL
authors.lastname: Heyward
authors.forename: J Tyler
authors.initials: JT
authors.lastname: Martin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000276:immunology; D016037:Single-Blind Method; D051217:Toll-Like Receptor 9 / Q000819:agonists; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C489630:1018 oligonucleotide
keywords: Hepatitis B vaccine; Randomized trial; Toll-like receptor 9