Safety, tolerability, pharmacokinetic characteristics, and immunogenicity of MW33: a Phase 1 clinical study of the SARS-CoV-2 RBD-targeting monoclonal antibody

Emerging Microbes and Infections

Shuhai Wang¹  Ruowan Li¹  Bei Zhao¹  Peipei Wang¹  Jinchao Zhang¹  Datao Liu¹  Jing Liu¹  Shaoqing Zeng¹  Song Lu¹  Yanqing Xiong²  Yan Lu²  Yijun Wu²  Xiaoyan Lin²  Liyan Zeng²  Xianmin Meng²  Hongzhou Lu²  Yan Wu² 

[1] Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, People’s Republic of China;Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China;

关键词: SARS-CoV-2;    COVID-19;    MW33 injection;    monoclonal antibody;    Phase 1 clinical trial;    safety;   

DOI  :  10.1080/22221751.2021.1960900

来源: DOAJ

【 摘 要 】

MW33 is a fully humanized IgG1κ monoclonal neutralizing antibody, and may be used for the prevention and treatment of coronavirus disease 2019 (COVID-19). We conducted a randomized, double-blind, placebo-controlled, single-dose, dose-escalation Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of MW33. Healthy adults aged 18–45 years were sequentially enrolled into the 4, 10, 20, 40, and 60 mg/kg dose groups and infused with MW33 over 60 ± 15 min and followed for 85 days. All 42 enrolled participants completed the MW33 infusion, and 40 participants completed the 85-day follow-up period. 34 participants received a single infusion of 4 (n = 2), 10 (n = 8), 20 (n = 8), 40 (n = 8), and 60 mg/kg (n = 8) of MW33. 27 subjects in the test groups experienced 78 adverse events (AEs) post-dose, with an incidence of 79.4% (27/34). The most common AEs included abnormal laboratory test results, vascular and lymphatic disorders, and infectious diseases. The severity of AEs was mainly Grade 1 (92 AEs), and three Grade 2 and one Grade 4. The main PK parameters, maximum concentration (Cmax), and area under the concentration-time curve (AUC0–t, and AUC0–∞) in 34 subjects showed a linear kinetic relationship in the range of 10–60 mg/kg. The plasma half-life was approximately 25 days. The positive rates of serum ADAs and antibody titres were low with no evidence of an impact on safety or PK. In conclusion, MW33 was well-tolerated, demonstrated linear PK, with a lower positive rate of serum ADAs and antibody titres in healthy subjects.Trial registration: ClinicalTrials.gov identifier: NCT04427501.Trial registration: ClinicalTrials.gov identifier: NCT04533048.Trial registration: ClinicalTrials.gov identifier: NCT04627584.

【 授权许可】

Unknown