A Randomized, Double-Blind, Controlled Phase III Clinical Trial to Evaluate the Immunogenicity and Safety of a Lyophilized Human Rabies Vaccine (Vero Cells) in Healthy Participants Aged 10–60 Years Following Essen and Zagreb Vaccination Procedures

Abstract

Objective: In this paper, we aim to show that the immunogenicity of the lyophilized human rabies vaccine (Vero cells) (investigational vaccine) developed by Dalian Aleph Biomedical Co., Ltd. in healthy participants aged 10–60 years old is non-inferior to the lyophilized PVRV (positive control) manufactured by Liaoning Chengda Biotechnology Co., Ltd. (Shenyang, China), and that its safety is clinically acceptable. Method: A total of 2776 participants were enrolled in this study and divided into four groups: a five-dose test group, a five-dose control group, a four-dose test group, and a four-dose control group. The patients in the four-dose groups (Zagreb) were vaccinated on Days 0 (two doses), 7 (one dose), and 21 (one dose), and those in the five-dose groups (Essen) were vaccinated on Days 0, 3, 7, 14, and 28 (one dose each). The rabies-virus-neutralizing antibody assay with the RFFIT was used to assess the immunogenicity, and the adverse events (AEs) and serious adverse events (SAEs) were identified and collated. Results: The positive seroconversion rate was up to 100% on Days 14 and 35/42 after vaccination following any procedures in pre-immunization antibody-negative participants, and the positive seroconversion rate and geometric mean concentration (GMC) of the test groups (Zagreb and Essen vaccination procedures) was not inferior to that of the control groups. On Day 7 after vaccination, the immunogenicity of the Zagreb procedure with two doses of the vaccine on Day 0 was superior to the Essen procedure with one dose of vaccine, that is, the former had a higher seroconversion rate and RVNA titer. The non-inferiority criterion of immunogenicity was met for the whole population, the population aged 10–18 years and ≥18 years, and the pre-immunization antibody-positive population. The incidences of all AEs, solicited AEs, and unsolicited AEs in both groups were not statistically significant, and no vaccination-related SAEs were observed. Conclusion: The investigated vaccine is safe, its immunogenicity is non-inferior to that of the control vaccine, and the efficacy of the Zagreb procedure is superior to that of the Essen procedure 7 days after the first dose.