Comparison of a novel human rabies monoclonal antibody to human rabies immunoglobulin for post-exposure prophylaxis: A phase 2/3 randomized, single blind, non-inferiority, controlled study

Abstract

Background: Lack of access to rabies immunoglobulin (RIG) contributes to the high rabies mortality. A recombinant human monoclonal antibody (SII RMAb) was tested in a post-exposure prophylaxis (PEP) regimen in comparison to a human RIG (HRIG)-containing PEP regimen. Methods: This was a Phase 2/3 randomized, single blind, non-inferiority study conducted in 200 participants with WHO category III suspected rabies exposures. On Day 0, participants received either SII RMAb or HRIG (1:1 ratio) into wounds and if required, intramuscularly (IM) along with five doses of rabies vaccine IM on Days 0, 3, 7, 14 and 28. The primary endpoint was the ratio of Day 14 geometric mean concentration (GMC) of RVNA activity as measured by RFFIT for SII RMAb recipients relative to HRIG recipients. Results: 199 participants received SII RMAb (101) or HRIG (98) and at least one dose of vaccine. The Day 14 GMC ratio of SII RMAb group to HRIG group was 4.23 (96.9018% CI 2.59 - 6.94) with the GMC for SII RMAb recipients of 24.90 IU/mL (95% CI 18.94 - 32.74) and 5.88 IU/mL (95% CI 4.11 - 8.41) for HRIG recipients. Majority of local injection site and systemic adverse reactions reported from bothgroups were mild to moderate in severity. Conclusions: A PEP regimen containing SII RMAb was safe and demonstrated non-inferiority to HRIG PEP in RVNA production. The novel monoclonal potentially offers a safe and potent alternative for the passive component of PEP and could significantly improve the management of bites from suspected rabid animals. Trial registration number: CTRI/2012/05/002709.