Sam Jackson1, Joseph Lentino2, James Kopp3, Linda Murray4, William Ellison5, Margaret Rhee6, Gerald Shockey7, Lalith Akella8, Kimberly Erby9, William L Heyward10, Robert S Janssen11. 1. Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: sjackson@alkahest.com. 2. Radiant Research, Inc., 515 North State Street, Suite 2700, Chicago, IL 60654, United States. Electronic address: josephlentino@radiantresearch.com. 3. Radiant Research, Inc., 1657 Greenville Street, Anderson, SC 29621, United States. Electronic address: jameskopp@radiantresearch.com. 4. Radiant Research, Inc., 6010 Park Blvd, Pinellas Park, FL 33781, United States. Electronic address: LindaMurray@radiantresearch.com. 5. Radiant Research, Inc., 322 Memorial Drive, Greer, SC 29650, United States. Electronic address: travisellison@radiantresearch.com. 6. Radiant Research, Inc., 530 South Main Street, Suite 1712, Akron, OH 44311, United States. Electronic address: MargaretRhee@radiantresearch.com. 7. Desert Clinical Research, LLC/Clinical Research Advantage, Inc., 2310 E. Brown Road, Mesa, AZ 85213, United States. Electronic address: gshockey@crastudies.com. 8. Stat Shop Inc., 425 1st street, San Francisco, CA 94105, United States. Electronic address: lalith.akella@statshopinc.com. 9. Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: kerby@dynavax.com. 10. Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: william_heyward@yahoo.com. 11. Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: rjanssen@dynavax.com.
Abstract
BACKGROUND: Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke. METHODS: Phase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status. RESULTS: Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group. CONCLUSION: Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier: NCT02117934.
RCT Entities:
BACKGROUND:Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke. METHODS: Phase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status. RESULTS: Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetesparticipants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group. CONCLUSION: Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier: NCT02117934.
Authors: Diane M Da Silva; Joseph G Skeate; Elena Chavez-Juan; Kim P Lühen; Jiun-Ming Wu; Chia-Mao Wu; W Martin Kast; KinKai Hwang Journal: Vaccine Date: 2019-04-19 Impact factor: 3.641
Authors: Carolyn B Bridges; Tureka L Watson; Noele P Nelson; Maribel Chavez-Torres; Patrick Fineis; Boatemaa Ntiri-Reid; Edward Wake; Judith M Leahy; Anita K Kurian; Mary Ann K Hall; Erin D Kennedy Journal: Vaccine Date: 2019-07-11 Impact factor: 3.641