Safety, tolerability, pharmacokinetic characteristics, and immunogenicity of MW33: a Phase 1 clinical study of the SARS-CoV-2 RBD-targeting monoclonal antibody
| Autor: | Xiaoyan Lin, Datao Liu, Song Lu, Yan Lu, Shaoqing Zeng, Jing Liu, Shuhai Wang, Hongzhou Lu, Xianmin Meng, Peipei Wang, Bei Zhao, Yijun Wu, Yan Wu, Ruowan Li, Yanqing Xiong, Jinchao Zhang, Liyan Zeng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Data Analysis Male safety Coronavirus disease 2019 (COVID-19) Epidemiology medicine.drug_class Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Immunology pharmacokinetic characteristics Phases of clinical research Monoclonal antibody Microbiology Antiviral Agents Severity of Illness Index MW33 injection Young Adult Pharmacokinetics Virology Drug Discovery Medicine Humans Neutralizing antibody biology business.industry SARS-CoV-2 Immunogenicity Antibodies Monoclonal COVID-19 General Medicine Phase 1 clinical trial COVID-19 Drug Treatment Infectious Diseases Treatment Outcome monoclonal antibody Monoclonal biology.protein Parasitology Female business Research Article |
| Zdroj: | Emerging Microbes & Infections article-version (VoR) Version of Record |
| ISSN: | 2222-1751 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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