ABSTRACT FINAL ID: 1780
TITLE: Peak Immunogenicity of Two Doses of Investigational HEPLISAV-B™ in Difficult to Vaccinate Individuals: Seroprotection Rates in Three Phase 3 Trials
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Background: Improved HBV vaccine immunogenicity is needed for certain populations who have reduced seroprotection rates with traditional vaccines. Three multi-center, observer-blinded, randomized, phase 3 studies, compared two doses of HEPLISAV-B (H) to three doses of Engerix-B® (E).
Methods: H (20 mcg rHBsAg combined with 3000 mcg 1018, a Toll-like receptor 9 agonist) was administered at 0 and 4 weeks, with placebo administered at 24 weeks. E (20 mcg rHBsAg) was administered at 0, 4 and 24 weeks. Peak seroprotection rates (SPR=proportion with anti-HBs ≥ 10 mIU/mL) were compared in analyses pooling the modified intent-to-treat (mITT) populations of the 3 trials.
Results: The 12,728 subjects in the mITT population had the following baseline characteristics that were well balanced across treatment groups: mean age 49.3 years, 49.0% men; 43.4% BMI ≥ 30 kg/m2; 78.0% white; 18.9% black; 30.7% smokers; 10.6% with diabetes mellitus; and 1.2% with chronic liver disease (hepatic steatosis 60.1%; HCV 27.4%, other 12.5%). The peak SPRs of H were statistically significantly higher (p value<0.01) than E when stratified according to factors that have previously been associated with reduced seroprotection rates (Table 1). Both vaccines were generally well-tolerated with the rate and severity of AEs being similar across the groups.
Conclusion: HEPLISAV-B given as 2 doses over 4 weeks induced significantly higher rates of seroprotection than Engerix-B given as 3 doses over 24 weeks in groups known to have reduced seroprotection rates as well as in groups known to have good responses to currently licensed hepatitis B vaccines.