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

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

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

Affiliations

  • 1 National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China. hjbian@fmmu.edu.cn.
  • 2 Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • 3 National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
  • 4 Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • 5 Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
  • 6 Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • 7 Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
  • 8 College of Military Preventive Medicine, Fourth Military Medical University, Xi'an, China.
  • 9 Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
  • 10 Department of Pathology, Fourth Military Medical University, Xi'an, China.
  • 11 Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, Changzhou, China.
  • 12 Department of Foreign Languages, Fourth Military Medical University, Xi'an, China.
  • 13 National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China. znchen@fmmu.edu.cn.
  • 14 Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. zhuping@fmmu.edu.cn.
  • # Contributed equally.
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 IgG2 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 Cmax 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.

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