Phase I Evaluation of Siltartoxatug, a First-in-Class Anti-Tetanus Monoclonal Antibody: Safety, Pharmacokinetics and Pharmacodynamics in Healthy Australian and Chinese Populations.

Abstract

Siltartoxatug, a first-in-class monoclonal antibody targeting tetanus toxin for post-exposure prophylaxis, was evaluated in two phase I trials in Australian and Chinese healthy adults. In these randomized, double-blind, placebo-controlled, dose-escalation studies, participants received a single intramuscular injection of siltartoxatug (10-250 μg/kg) or placebo. The primary objectives were to assess safety, with secondary goals evaluating pharmacokinetics (PK) and immunogenicity, and pharmacodynamics (PD) as an exploratory. Siltartoxatug demonstrated an excellent safety profile across all doses, with adverse event (AE) rates comparable to placebo and no serious adverse events (SAE) attributed to the drug. PK analysis revealed dose-proportional exposure, and the PK profile exhibited characteristics typical of an IgG1 monoclonal antibody. PK parameters were highly consistent between Australian and Chinese trials, indicating no apparent ethnic differences in drug disposition. A single dose rapidly induced protective anti-tetanus antibody titers (≥ 0.01 IU/mL), with all participants in the 100 and 250 μg/kg cohorts achieving seroprotection within 48 hours post-dose; 100% seroprotection was sustained through 105 days in the 250 μg/kg cohort, and remained high (≥ 83.3%) through Day 85 in the 100 μg/kg cohort. Immunogenicity was minimal. These findings collectively highlighted siltartoxatug's potential as a next-generation passive immunizing agent. The consistent PK/PD profiles between Australian and Chinese populations suggested no apparent ethnic differences, providing a foundation for extrapolating efficacy findings from the Chinese trials to other racial groups.