Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial PMID: 34001849

Target-related Cytokines

2026-09-23

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

1. National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China. [email protected].
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. [email protected].
14. Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. [email protected].
# Contributed equally.

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 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.