Meplazumab, a CD147 antibody, for severe COVID-19: a double-blind, randomized, placebo-controlled, phase 3 clinical trial
Huijie Bian, Liang Chen, Zheng Zhang, Ai-Dong Wen, Zhao-Hui Zheng, Li-Qiang Song, Meng-Ying Yao, Ying-Xia Liu, Xi-Jing Zhang, Hong-Lin Dong, Jian-Qi Lian, Lei Pan, Yu Liu, Xing Gu, Hui Zhao, Jing-Wen Wang, Qing-Yi Wang, Kui Zhang, Jun-Feng Jia, Rong-Hua Xie, Xing Luo, Xiang-Hui Fu, Yan-Yan Jia, Jun-Na Hou, Qiu-Yue Tan, Xiao-Xia Chen, Liu-Qing Yang, Yuan-Long Lin, Xiao-Xia Wang, Lei Zhang, Qin-Jing Zeng, Wen-Jie Li, Rui-Xuan Wang, Yang Zhang, Xiu-Xuan Sun, Bin Wang, Xu Yang, Jian-Li Jiang, Ling Li, Jiao Wu, Xiang-Min Yang, Hai Zhang, Ying Shi, Xiao-Chun Chen, Hao Tang, Hong-Wei Shi, Shuang-Shuang Liu, Yong Yang, Tian-Yi Yang, Ding Wei, Zhi-Nan Chen, Ping Zhu
Signal Transduction and Targeted Therapy, doi:10.1038/s41392-025-02208-9
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 allcause 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 grade ≥ 3 TEAEs observed. These promising results indicate that meplazumab reduces mortality and enhances clinical benefits in severe COVID-19 patients with a good safety profile, providing effective and specific therapeutics for severe COVID-19 (the trial was registered at ClinicalTrials.gov (NCT05679479)).
AUTHOR CONTRIBUTIONS Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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