tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2021 May 17;6(1):194.
doi: 10.1038/s41392-021-00603-6.
Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial
Huijie Bian[SUP] #[/SUP][SUP] 1 [/SUP], Zhao-Hui Zheng[SUP] #[/SUP][SUP] 2 [/SUP], Ding Wei[SUP] #[/SUP][SUP] 3 [/SUP], Aidong Wen[SUP] #[/SUP][SUP] 4 [/SUP], Zheng Zhang[SUP] #[/SUP][SUP] 3 [/SUP], Jian-Qi Lian[SUP] #[/SUP][SUP] 5 [/SUP], Wen-Zhen Kang[SUP] #[/SUP][SUP] 5 [/SUP], Chun-Qiu Hao[SUP] #[/SUP][SUP] 5 [/SUP], Jing Wang[SUP] #[/SUP][SUP] 6 [/SUP], Rong-Hua Xie[SUP] 2 [/SUP], Ke Dong[SUP] 7 [/SUP], Jie-Lai Xia[SUP] 8 [/SUP], Jin-Lin Miao[SUP] 3 [/SUP], Wen Kang[SUP] 5 [/SUP], Guoquan Li[SUP] 6 [/SUP], Di Zhang[SUP] 4 [/SUP], Mingru Zhang[SUP] 6 [/SUP], Xiu-Xuan Sun[SUP] 3 [/SUP], Likun Ding[SUP] 4 [/SUP], Kui Zhang[SUP] 2 [/SUP], Junfeng Jia[SUP] 2 [/SUP], Jin Ding[SUP] 2 [/SUP], Zhiqin Li[SUP] 2 [/SUP], Yanyan Jia[SUP] 4 [/SUP], Lin-Na Liu[SUP] 9 [/SUP], Zhe Zhang[SUP] 7 [/SUP], Zhao-Wei Gao[SUP] 7 [/SUP], Hong Du[SUP] 5 [/SUP], Na Yao[SUP] 5 [/SUP], Qing Wang[SUP] 2 [/SUP], Ke Wang[SUP] 3 [/SUP], Jie-Jie Geng[SUP] 3 [/SUP], Bin Wang[SUP] 3 [/SUP], Ting Guo[SUP] 3 [/SUP], Ruo Chen[SUP] 3 [/SUP], Yu-Meng Zhu[SUP] 3 [/SUP], Li-Juan Wang[SUP] 3 [/SUP], Qian He[SUP] 3 [/SUP], Rui-Rui Yao[SUP] 3 [/SUP], Ying Shi[SUP] 3 [/SUP], Xiang-Min Yang[SUP] 3 [/SUP], Jian-Sheng Zhou[SUP] 3 [/SUP], Yi-Nan Ma[SUP] 3 [/SUP], Ya-Tao Wang[SUP] 3 [/SUP], Xue Liang[SUP] 3 [/SUP], Fei Huo[SUP] 3 [/SUP], Zhe Wang[SUP] 10 [/SUP], Yang Zhang[SUP] 3 [/SUP], Xu Yang[SUP] 3 [/SUP], Ye Zhang[SUP] 5 [/SUP], Lu-Hua Gao[SUP] 5 [/SUP], Ling Wang[SUP] 8 [/SUP], Xiao-Chun Chen[SUP] 11 [/SUP], Hao Tang[SUP] 11 [/SUP], Shuang-Shuang Liu[SUP] 11 [/SUP], Qing-Yi Wang[SUP] 12 [/SUP], Zhi-Nan Chen[SUP] 13 [/SUP], Ping Zhu[SUP] 14 [/SUP]
Affiliations
Abstract
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[SUB]2[/SUB] 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[SUB]max[/SUB] 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.
. 2021 May 17;6(1):194.
doi: 10.1038/s41392-021-00603-6.
Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial
Huijie Bian[SUP] #[/SUP][SUP] 1 [/SUP], Zhao-Hui Zheng[SUP] #[/SUP][SUP] 2 [/SUP], Ding Wei[SUP] #[/SUP][SUP] 3 [/SUP], Aidong Wen[SUP] #[/SUP][SUP] 4 [/SUP], Zheng Zhang[SUP] #[/SUP][SUP] 3 [/SUP], Jian-Qi Lian[SUP] #[/SUP][SUP] 5 [/SUP], Wen-Zhen Kang[SUP] #[/SUP][SUP] 5 [/SUP], Chun-Qiu Hao[SUP] #[/SUP][SUP] 5 [/SUP], Jing Wang[SUP] #[/SUP][SUP] 6 [/SUP], Rong-Hua Xie[SUP] 2 [/SUP], Ke Dong[SUP] 7 [/SUP], Jie-Lai Xia[SUP] 8 [/SUP], Jin-Lin Miao[SUP] 3 [/SUP], Wen Kang[SUP] 5 [/SUP], Guoquan Li[SUP] 6 [/SUP], Di Zhang[SUP] 4 [/SUP], Mingru Zhang[SUP] 6 [/SUP], Xiu-Xuan Sun[SUP] 3 [/SUP], Likun Ding[SUP] 4 [/SUP], Kui Zhang[SUP] 2 [/SUP], Junfeng Jia[SUP] 2 [/SUP], Jin Ding[SUP] 2 [/SUP], Zhiqin Li[SUP] 2 [/SUP], Yanyan Jia[SUP] 4 [/SUP], Lin-Na Liu[SUP] 9 [/SUP], Zhe Zhang[SUP] 7 [/SUP], Zhao-Wei Gao[SUP] 7 [/SUP], Hong Du[SUP] 5 [/SUP], Na Yao[SUP] 5 [/SUP], Qing Wang[SUP] 2 [/SUP], Ke Wang[SUP] 3 [/SUP], Jie-Jie Geng[SUP] 3 [/SUP], Bin Wang[SUP] 3 [/SUP], Ting Guo[SUP] 3 [/SUP], Ruo Chen[SUP] 3 [/SUP], Yu-Meng Zhu[SUP] 3 [/SUP], Li-Juan Wang[SUP] 3 [/SUP], Qian He[SUP] 3 [/SUP], Rui-Rui Yao[SUP] 3 [/SUP], Ying Shi[SUP] 3 [/SUP], Xiang-Min Yang[SUP] 3 [/SUP], Jian-Sheng Zhou[SUP] 3 [/SUP], Yi-Nan Ma[SUP] 3 [/SUP], Ya-Tao Wang[SUP] 3 [/SUP], Xue Liang[SUP] 3 [/SUP], Fei Huo[SUP] 3 [/SUP], Zhe Wang[SUP] 10 [/SUP], Yang Zhang[SUP] 3 [/SUP], Xu Yang[SUP] 3 [/SUP], Ye Zhang[SUP] 5 [/SUP], Lu-Hua Gao[SUP] 5 [/SUP], Ling Wang[SUP] 8 [/SUP], Xiao-Chun Chen[SUP] 11 [/SUP], Hao Tang[SUP] 11 [/SUP], Shuang-Shuang Liu[SUP] 11 [/SUP], Qing-Yi Wang[SUP] 12 [/SUP], Zhi-Nan Chen[SUP] 13 [/SUP], Ping Zhu[SUP] 14 [/SUP]
Affiliations
- PMID: 34001849
- DOI: 10.1038/s41392-021-00603-6
Abstract
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[SUB]2[/SUB] 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[SUB]max[/SUB] 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.