721. Immunogenicity of Two Doses of Investigational HEPLISAV (HBsAg-1018 ISS) Compared to Three Doses of Licensed Hepatitis B Vaccine (ENGERIX-B) in Type II Diabetics
Session: Poster Abstract Session: Vaccine Studies, Adjuvants, and Discovery
Friday, October 21, 2011
Room: Poster Hall B1
Background: Diabetics are at higher risk for hepatitis B infection and its sequelae, and are commonly less responsive to currently licensed hepatitis B vaccines. A multicenter, observer-blinded, phase 3 study was conducted in 2449 persons 40-70 years of age, comparing two doses of HEPLISAV (H) (20μg rHBsAg combined with 3000μg 1018 immunostimulatory sequence (ISS), a toll-like receptor 9 agonist) given at 0 and 4 weeks (placebo at 24 weeks) to three doses of Engerix-B (E) given at 0, 4 and 24 weeks.

Methods: This study was randomized in a 3:1 ratio, H to E. The aim was to determine if the immunogenicity of H is non-inferior/superior to E by comparing seroprotection rates (SPR = anti-HBs ≥ 10mIU/mL) 8 weeks post last dose of vaccine (week 12 vs 32, respectively) in the per protocol (PP) population. A prospective subgroup analysis was planned to compare the immunogenicity of these two vaccines in type II diabetics. Subjects with diabetes were prospectively determined based on medical history.

Results: Of the 1482 subjects in the PP population (1123 H; 359 E), the SPR was 90.0% at week 12 in the H group and 70.5% at week 32 in the E group with a SPR difference of 19.4% (95% CI: 14.7%, 24.7%) (p< 0.0001), indicating non-inferiority and superiority of H. Of the 129 diabetics in the PP population (99 H; 30 E), the SPRs for H were significantly greater than the SPRs for E at all time points.  At week 12 the SPR was 73.7% (n=73/99) in the H group and 10% (n=3/30) in the E group (p< 0.0001).  At the time point for the primary comparison of the study, the SPR was 73.7% (n=73/99) in the H group at week 12 and 63.3% (n=19/30) in the E group at week 32 demonstrating non-inferiority with a SPR difference of 10.4% (95% CI: -6.9%, 29.7%). H was superior to E at weeks 8, 12, 18, 24, 32, 36, and 44.  Furthermore, the SPR in the H group peaked at 84.8% at week 28 and declined to 83.5% by week 44 whereas the SPR in the E group peaked at 79.3% at week 28 and declined to 56.5% by week 44.

Conclusion: In a prospective subset analysis of adults with type II diabetes, HEPLISAV given as 2 doses over 4 weeks protected a significantly greater proportion of subjects in a shorter time and with longer lasting protection than Engerix-B given as 3 doses over 24 weeks.

Subject Category: I. Adult and Pediatric Vaccines

William L. Heyward, MD, Sean Bennett, MD, Elizabeth Fung, Fang Xie, PhD and J. Martin Sr., MD, Dynavax Technologies Corporation, Berkeley, CA


W. L. Heyward, Dynavax Technologies Corporation: Employee, Salary

S. Bennett, Dynavax Technologies Corporation: Employee, Salary

E. Fung, Dynavax Technologies Corporation: Employee, Salary

F. Xie, Dynavax Technologies Corporation: Consultant, Consulting fee

J. Martin Sr., Dynavax Technologies Corporation: Board Member and Employee, Salary

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.