Collaborators (34)
Author information
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.
12
Radiant Research, Inc., Murray, UT, United States.
13
Radiant Research, Inc., Aurora, CO, United States.
14
Central Arizona Medical Associates/Clinical Research Advantage, Inc., Mesa, AZ, United States.
15
Clinical Research Advantage, Inc., Henderson, NV, United States.
16
East Valley Family Physicians, PLC/Clinical Research Advantage, Inc., Chandler, AZ, United States.
17
Fiel Family and Sports Medicine, PC/Clinical Research Advantage, Inc., Tempe, AZ, United States.
18
Skyline Medical Center/Clinical Research Advantage, Inc., Elkhorn, NE, United States.
19
Family Practice Specialists/Clinical Research Advantage, Inc., Phoenix, AZ, United States.
20
Primary Care Associates/Clinical Research Advantage, Inc., Anderson, SC, United States.
21
Plano Internal Medicine/Clinical Research Advantage, Inc., Plano, TX, United States.
22
Thunderbird Internal Medicine/Clinical Research Advantage, Inc., Glendale, AZ, United States.
23
Cassidy Medical Group/Clinical Research Advantage, Inc., Vista, CA, United States.
24
Radiant Research, Inc., Santa Rosa, CA, United States.
25
Family Medicine Associates/Clinical Research Advantage, Inc., Evansville, IN, United States.
26
Radiant Research, Inc., San Antonio, TX, United States.
27
Clinix Health Services of Colorado/Clinical Research Advantage, Inc., Centennial, CO, United States.
28
Ridge Family Practice, PC/Clinical Research Advantage, Inc., Council Bluffs, IA, United States.
29
Simon Williamson Clinic/Clinical Research Advantage, Inc., Birmingham, AL, United States.
30
Radiant Research, Inc., Tucson, AZ, United States.
31
Tatum Highlands Medical Associates/Clinical Research Advantage, Inc., Phoenix, AZ, United States.
32
Clifford J. Molin, MD, LTD/Clinical Research Advantage, Inc., Las Vegas, NV, United States.
33
Radiant Research, Inc., Cincinnati, OH, United States.
34
Radiant Research, Inc., Edina, MN, United States.
35
Radiant Research, Inc., Dallas, TX, United States.
36
Central Phoenix Medical Clinic, LLC/Clinical Research Advantage, Inc., Phoenix, AZ, United States.
37
Radiant Research, Inc., Columbus, OH, United States.
38
Radiant Research, Inc., Chandler, AZ, United States.
39
Colorado Springs Health Partners - East/Clinical Research Advantage, Inc., Colorado Springs, CO, United States.
40
Radiant Research, Inc., Scottsdale, AZ, United States.
41
Radiant Research, Inc., St. Louis, MO, United States.
42
Radiant Research, Inc., Atlanta, GA, United States.
43
Warner Family Practice/Clinical Research Advantage Inc., Chandler, AZ, United States.
44
Prairie Fields Family Medicine/Clinical Research Advantage, Inc., Fremont, NE, United States.
45
Primary Care Physicians, LLP/Clinical Research Advantage, Inc., Omaha, NE, United States.
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.