Emerg Microbes Infect . Safety, tolerability, pharmacokinetic characteristics, and immunogenicity of MW33: A Phase 1 clinical study of the SARS-CoV-2 RBD-targeting monoclonal antibody

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Emerg Microbes Infect


. 2021 Aug 4;1-11.
doi: 10.1080/22221751.2021.1960900. Online ahead of print.
Safety, tolerability, pharmacokinetic characteristics, and immunogenicity of MW33: A Phase 1 clinical study of the SARS-CoV-2 RBD-targeting monoclonal antibody


Xianmin Meng ¹ , Peipei Wang ² , Yanqing Xiong ¹ , Yijun Wu ¹ , Xiaoyan Lin ¹ , Song Lu ² , Ruowan Li ² , Bei Zhao ² , Jing Liu ² , Shaoqing Zeng ² , Liyan Zeng ¹ , Yan Wu ¹ , Yan Lu ¹ , Jinchao Zhang ² , Datao Liu ² , Shuhai Wang ² , Hongzhou Lu ¹



Affiliations

• PMID: 34346827
• DOI: 10.1080/22221751.2021.1960900

Abstract

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 (C_max), and area under the concentration-time curve (AUC_0-t, and AUC_0-∞) in 34 subjects showed a linear kinetic relationship in the range of 10 to 60 mg/kg. The plasma half-life was approximately 25 days. The positive rates of serum ADAs and antibody titers 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 titers in healthy subjects.Trial registration: ClinicalTrials.gov identifier: NCT04427501..Trial registration: ClinicalTrials.gov identifier: NCT04533048..Trial registration: ClinicalTrials.gov identifier: NCT04627584..

Keywords: COVID-19; MW33 Injection; Monoclonal Antibody; Pharmacokinetic Characteristics; Phase 1 Clinical Trial; SARS-CoV-2; Safety.