Recombinant monoclonal antibody siltartoxatug versus plasma-derived human tetanus immunoglobulin for tetanus: a randomized, double-blind, active-controlled, phase 3 trial

Summary

This double-blind phase 3 trial randomized 675 patients with tetanus-prone wounds 2:1 to siltartoxatug 10 mg IM or human tetanus immunoglobulin (HTIG) 250 IU. The primary surrogate endpoint, increase in neutralizing antibody titer of at least 0.01 IU/mL, occurred in 95.4% versus 53.2%; absolute difference 42.3% (95% CI 35.5-49.1; P<.0001). Overall adverse events were similar (38.2% versus 33.9%).

Why it matters

A recombinant monoclonal antibody could eventually provide a scalable alternative to blood-derived HTIG for tetanus postexposure prophylaxis. It should not change US ED practice on this evidence alone: clinical tetanus prevention was not the primary endpoint, and regulatory availability outside China was not established in the sources reviewed.

Main findings

• Primary surrogate endpoint occurred in 95.4% with siltartoxatug versus 53.2% with HTIG; absolute difference 42.3% (95% CI 35.5-49.1; P<.0001).
• Overall adverse events occurred in 168/440 (38.2%) versus 75/221 (33.9%).
• Publisher full text reported allergic reactions in 1/440 (0.2%) versus 2/221 (0.9%).
• The trial supports passive immunogenicity but was not powered around clinical tetanus incidence.

Limitations

The primary endpoint was a neutralizing-antibody surrogate rather than clinical tetanus, participants were recruited in China, and manufacturer employees were among the authors. The product was approved in China, but these data do not establish standard-of-care status in the United States.