Neutralizing antibody activity, safety and immunogenicity of human anti-rabies virus monoclonal antibody (Ormutivimab) in Chinese healthy adults: A phase Ⅱb randomized, double-blind, parallel-controlled study

This study was a randomized, double-blind, parallel-controlled trail to evaluate the rabies virus neutralizing activity（RVNA）, safety and immunogenicity of Ormutivimab + rabies vaccine in Chinese healthy adults. Subjects were randomly and equally assigned to 4 groups (20 IU/kg Omtv + vaccine, 40 IU/kg Omtv + vaccine, 20 IU/kg HRIG + vaccine, and placebo + vaccine). Subjects received vaccine as the WHO Essen regime combined with Omutivimab、HRIG or placebo on Day 0. The study lasted for 43 days. A total of 240 subjects were simultaneously assigned to both FAS and SS. Fifty subjects with baseline RVNA > 0.05 IU/ml (detection limit) were excluded, 190 were included into mITT. All the subjects from 40 IU/kg Omtv + vaccine group had a protection level of RNVA (≥0.5 IU/ml, WHO) on Day 14, and those in 20 IU/kg Omtv + vaccine group and placebo + vaccine group converted positive 100 % on Day 28. In contrast to 20 IU/kg HRIG + vaccine and placebo + vaccine, Ormutivimab + vaccine provided a higher RVNA during Days 0 to 7. And RVNA in 40 IU/kg Omtv + vaccine and 20 IU/kg Omtv + vaccine groups were always higher than 20 IU/kg HRIG + vaccine group during the whole study. Although anti-Omtv antibody were detected in some subjects, it did not influence the RVNA. The incidence of adverse reactions was significantly lower in 20 IU/kg Omtv + vaccine group (17.2 %) than in 40 IU/kg Omtv + vaccine (36.7 %) and 20 IU/kg HRIG + vaccine groups (40.3 %). Compared with HRIG + vaccine and placebo + vaccine, Omtv + vaccine provided higher RNVA for earlier immune protection. The interference of Ormutivimab on the long-term immune protection induced by rabies vaccine is weaker than HRIG. At the same dose, the adverse reactions of Omtv + vaccine group were less than HRIG + vaccine group. Registration: ClinicalTrials.gov #NCT02559921.