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

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

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.