Phase III PROTECT study of Sci-B-Vac meets endpoints in hepatitis B

VBI Vaccines announced positive top-line results from the randomized, double-blind, pivotal Phase III study, PROTECT, designed to evaluate the efficacy and safety of a 10 µg dose of Sci-B-Vac, the company’s trivalent hepatitis B vaccine, compared with a 20 µg dose of the comparator vaccine, Engerix-B. The study, which enrolled a total of 1,607 adults, of which approximately 80% were aged at least 45 years, met both of its co-primary endpoints. This included non-inferiority of seroprotection rate (SPR) of Sci-B-Vac vs. Engerix-B in all subjects age of at least 18 years, 4 weeks after 3rd vaccination (at day 196).

The SPR in all subjects age at least 18 years who received Sci-B-Vac was 91.4% compared with 76.5% for subjects who received Engerix-B. The SPR in the Sci-B-Vac cohort was statistically significantly higher than the SPR in the Engerix-B cohort – SPR difference: 14.9%; 95% confidence interval (CI) [11.2%, 18.6%]. Superiority of SPR of Sci-B-Vac vs. Engerix-B was seen in subjects aged at least 45 years, 4 weeks after 3rd vaccination (at day 196). The SPR in subjects aged at least 45 years who received Sci-B-Vac was 89.4% compared with 73.1% for subjects who received Engerix-B. Superiority of Sci-B-Vac vs. Engerix-B was achieved in subjects aged at least 45 years – SPR difference: 16.4%; 95% CI [12.2%, 20.7%]. Moreover, the SPR of Sci-B-Vac compared with Engerix-B was statistically significantly higher in all key subgroup analyses of adults aged at least 18 years, including by age, gender, body mass index (BMI), diabetic status, and smoking status, 4 weeks after 3rd vaccination (at day 196).

In diabetics, the SPR in subjects who received Sci-B-Vac was 83.3% compared with 58.3% for subjects who received Engerix-B – SPR difference: 25.0%; 95% CI [8.4%, 40.4%]. In subjects with a body mass index (BMI) above 30, the SPR in subjects who received Sci-B-Vac was 89.2% compared with 68.1% for subjects who received Engerix-B – SPR difference: 21.1%; 95% CI [14.3%, 28.0%]. The safety and tolerability seen in PROTECT was consistent with the known safety profile of Sci-B-Vac®, with no new safety risks identified and no safety signals observed in either study cohort. Moreover, there were no observed clusters or unusual patterns of adverse events – the adverse events were generally consistent with characteristics of the study population.

Comment: The non-inferiority analysis of two doses of Sci-B-Vac compared with three doses of Engerix-B in subjects age 18-45 years will be reassessed based on the complete integrated data analyses from both the PROTECT and the CONSTANT studies. The top-line data from the CONSTANT study is expected around year-end 2019. Successful completion of the second pivotal Phase III study, CONSTANT, is required for the Biologics License Application (BLA) to the FDA, the MAAs to the EMA, and the New Drug Submission (NDS) to Health Canada.