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

Disclosures:

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.