Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial

• Published in: Signal transduction and targeted therapy Vol. 6; no. 1; pp. 194 - 11
• Main Authors: Bian, Huijie, Zheng, Zhao-Hui, Wei, Ding, Wen, Aidong, Zhang, Zheng, Lian, Jian-Qi, Kang, Wen-Zhen, Hao, Chun-Qiu, Wang, Jing, Xie, Rong-Hua, Dong, Ke, Xia, Jie-Lai, Miao, Jin-Lin, Kang, Wen, Li, Guoquan, Zhang, Di, Zhang, Mingru, Sun, Xiu-Xuan, Ding, Likun, Zhang, Kui, Jia, Junfeng, Ding, Jin, Li, Zhiqin, Jia, Yanyan, Liu, Lin-Na, Zhang, Zhe, Gao, Zhao-Wei, Du, Hong, Yao, Na, Wang, Qing, Wang, Ke, Geng, Jie-Jie, Wang, Bin, Guo, Ting, Chen, Ruo, Zhu, Yu-Meng, Wang, Li-Juan, He, Qian, Yao, Rui-Rui, Shi, Ying, Yang, Xiang-Min, Zhou, Jian-Sheng, Ma, Yi-Nan, Wang, Ya-Tao, Liang, Xue, Huo, Fei, Wang, Zhe, Zhang, Yang, Yang, Xu, Zhang, Ye, Gao, Lu-Hua, Wang, Ling, Chen, Xiao-Chun, Tang, Hao, Liu, Shuang-Shuang, Wang, Qing-Yi, Chen, Zhi-Nan, Zhu, Ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.05.2021; Nature Publishing Group
• Subjects: 692/4017; 692/699/255; Adolescent; Adult; Antibodies; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - pharmacokinetics; Cancer Research; Cell Biology; Coronaviruses; COVID-19; COVID-19 - metabolism; COVID-19 - pathology; COVID-19 Drug Treatment; Double-Blind Method; Female; Humans; Internal Medicine; Lung - metabolism; Lung - pathology; Lung - virology; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Pathology; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome coronavirus 2
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-021-00603-6

s Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG 2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C max and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged ( P  = 0.005) and case severity ( P  = 0.021), and reduced the time to virus negative ( P  = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.