Recombinant monoclonal antibody siltartoxatug versus plasma-derived human tetanus immunoglobulin for tetanus: a randomized, double-blind, active-controlled, phase 3 trial
Zijing Liang, Si Liu, Wei Guo, Z. Y. Deng, Wenkai Bin, Anyong Yu, Junyan Hu, Lidong Wu, Zhanfei Li, Weijin Huang, He Li, Dapeng Cheng, Shugui Li, Qinghao Guo, Dongshan Zhang, Xinming Yan, Chunlei Wang, Wenwei Cai, Banghan Ding, Wenqiang Li, Li Xu, Bin Xu, Lei He, Yanhong Ouyang, Hong Zhan, Jianwei Wang, Yan Zhao, Xinyu Liu, Wenxi Xiang, Meizhuo Zhang, Zhihua Zhang, Jiyuan Ding, Xiaohu Kuang, Weihong Zheng, Hua‐Xin Liao, Wanmei Wang, Wang Chuanlin
Abstract
Abstract Tetanus remains an important global public health concern. Currently, the only recommended passive immunization therapy for tetanus prophylaxis is plasma-derived human tetanus immunoglobulin (HTIG), which faces a global supply shortage and can transmit infectious pathogens. Despite not being endorsed by WHO due to safety concerns, equine tetanus antitoxin remains widely used in some countries. We conducted a randomized, double-blind, phase 3 trial to evaluate siltartoxatug—a first-in-class recombinant monoclonal antibody—for tetanus postexposure prophylaxis. Participants ( n = 675) were randomized (2:1) to receive a single intramuscular injection of siltartoxatug 10 mg or HTIG 250 IU. The study met its primary outcome, with siltartoxatug demonstrating superiority to HTIG in the proportion of participants with an increase of anti-tetanus neutralizing antibody titers from baseline (ΔTiter) ≥ 0.01 IU ml − 1 (95.4% versus 53.2%; intergroup difference 42.3% (95% confidence interval, 35.5–49.1; P < 0.0001)). The safety profiles were comparable, with similar incidence of adverse events between the siltartoxatug (38.2%, 168 of 440) and HTIG (33.9%, 75 of 221) groups. These findings highlight siltartoxatug as an effective and safe option for passive immunization against tetanus. ClinicalTrials.gov registration: NCT05664750 .