Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial
Huijie Bian, Zhaohui Zheng, Ding Wei, Aidong Wen, Zheng Zhang, Jianqi Lian, Wenzhen Kang, Chun-Qiu Hao, Jing Wang, Xie Rong-hua, Ke Dong, Jielai Xia, Jinlin Miao, Wen Kang, Guoquan Li, Di Zhang, Mingru Zhang, Xiuxuan Sun, Likun Ding, Kui Zhang, Junfeng Jia, Jin Ding, Zhiqin Li, Yanyan Jia, Linna Liu, Zhe Zhang, Zhaowei Gao, Hong Du, Na Yao, Qing Wang, Ke Wang, Jiejie Geng, Bin Wang, Ting Guo, Ruo Chen, Yumeng Zhu, Lijuan Wang, Qian He, Rui-Rui Yao, Ying Shi, Xiangmin Yang, Jiansheng Zhou, Yinan Ma, Yatao Wang, Xue Liang, Fei Huo, Zhe Wang, Yang Zhang, Xu Yang, Ye Zhang, Lu-Hua Gao, Ling Wang, Xiaochun Chen, Hao Tang, Shuangshuang Liu, Qingyi Wang, Zhi‐Nan Chen, Ping Zhu
Abstract
Abstracts 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.