Meplazumab, a CD147 antibody, for severe COVID-19: a double-blind, randomized, placebo-controlled, phase 3 clinical trial

作者：Huijie Bian, Chen Liang, Zheng Zhang, Aidong Wen, Zhaohui Zheng, Liqiang Song, Mengying Yao, Yingxia Liu, Xijing Zhang, Honglin Dong, Jianqi Lian, Lei Pan, Yu Liu, Xing Gu, Hui Zhao, Jingwen Wang, Qingyi Wang, Kui Zhang, Junfeng Jia, Xie Rong-hua, Xing Luo, Xianghui Fu, Yanyan Jia, Junna Hou, Qiuyue Tan, Xiaoxia Chen, Liuqing Yang, Yuanlong Lin, Xiaoxia Wang, Lei Zhang, Qin-Jing Zeng, Wenjie Li, Ruixuan Wang, Yang Zhang, Xiuxuan Sun, Bin Wang, Yang Xu, Jian-Li Jiang, Ling Li, Jiao Wu, Xiang-Min Yang, Hai Feng Zhang, Ying Shi, Xiaochun Chen, Hao Tang, Hongwei Shi, Shuangshuang Liu, Yong Yang, Tianyi Yang, Wei Ding, Zhi‐Nan Chen, Ping Zhu · 发表于：Signal Transduction and Targeted Therapy · 年份：2025 · DOI：10.1038/s41392-025-02208-9 · 被引用次数：4 · 研究领域：Signaling Pathways in Disease、Sepsis Diagnosis and Treatment、Intensive Care Unit Cognitive Disorders

Meplazumab, a humanized CD147 antibody, showed favorable safety and clinical benefits in phase 1 and phase 2/3 seamless clinical studies. Further evaluation of its therapeutic efficacy in patients with severe COVID-19 is needed. In this phase 3 add-on study, we randomized patients with severe COVID-19 in a 1:1 ratio to receive 0.2 mg/kg meplazumab or placebo via intravenous injection, and evaluated efficacy and safety within 56 days. Between February 2023 and November 2023, 108 patients with severe COVID-19 were randomized to two groups, with their baseline characteristics generally balanced. The primary endpoint, 28-day all-cause mortality was 1.96% in the meplazumab group vs 7.69% in the placebo group (P = 0.1703). Supplementary analysis using composite strategy indicated a significant reduction of 28-day all-cause mortality in meplazumab compared to placebo (3.92% vs 15.38%, P = 0.044). Meplazumab also significantly reduced the mortality in smoking subjects on day 28 (P = 0.047) compared to placebo in supplementary analysis. The secondary endpoint, 56-day all-cause mortality, was 1.96% in the meplazumab group and 11.54% in the placebo group (P = 0.048), which was 3.92% and 15.38%, respectively (P = 0.044) by supplementary analysis. Additional secondary endpoints showed potential benefits, including increased hospital discharge rates, improved clinical outcomes, and improved viral nucleotide conversion rate. Meplazumab demonstrated good safety and tolerability, with no grad...