Safety, tolerability, pharmacokinetics, and immunogenicity of an anti-SARS-CoV-2 monoclonal antibody HFB30132A after single dose intravenous administration in healthy Chinese subjects: a phase 1, randomized, double-blind, placebo-controlled study

Frontiers in Pharmacology

Pharmacology

Chao Qiu¹  Ke Lin¹  Wenhong Zhang²  Liang Schweizer²  Angela Liu²  Francisco Adrian²  He Zhou²  Shanshan Li³  Jingwen Gu³  Xiaojie Wu⁴  Nanyang Li⁴  Jinjie He⁴  Yuancheng Chen⁴  Guoying Cao⁴  Haijing Yang⁴  Jingjing Wang⁴  Jufang Wu⁴  Size Li⁴  Jing Zhang⁵ 

[1] Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China;HiFiBiO (Hang Zhou) Ltd., Shanghai, China;Huashan Worldwide Medical Center, Huashan Hospital, Fudan University, Shanghai, China;Phase 1 Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China;Phase 1 Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China;Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China;

关键词: neutralizing antibody;    monoclonal antibody;    SARS-CoV-2;    HFB30132A;    COVID-19;    safety;    pharmacokinetics;    immunogenicity;   

DOI  :  10.3389/fphar.2023.1117293

 received in 2022-12-06, accepted in 2023-05-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

Objective: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) still protracts worldwide. HFB30132A is an anti- SARS-CoV-2 monoclonal antibody purposely engineered for an extended half-life with neutralizing activity against majority of the virus variants identified so far. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of HFB30132A in healthy Chinese subjects.Methods: A phase 1, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. Twenty subjects were enrolled to Cohort 1 (1,000 mg dose level, 10 subjects) or Cohort 2 (2,000 mg dose level, 10 subjects). Subjects in each cohort were assigned randomly to receive a single intravenous (IV) dose of HFB30132A or placebo at a ratio of 8:2. Safety was assessed in terms of treatment emergent adverse events (TEAEs), vital signs, physical examination, laboratory tests, and ECG findings. PK parameters were measured and calculated appropriately. Anti-drug antibody (ADA) test was performed to detect anti-HFB30132A antibodies.Results: All subjects completed the study. Overall, 13 (65%) of the 20 subjects experienced TEAEs. The most common TEAEs were laboratory abnormalities (12 subjects [60%]), gastrointestinal disorders (6 subjects [30%]), and dizziness (4 subjects [20%]). All TEAEs were Grade 1 or Grade 2 in severity based on the criteria of Common Terminology Criteria for Adverse Events (CTCAE). Serum exposure (Cmax, AUC0-t, AUC0-∞) of HFB30132A increased with ascending dose. After single dose of 1,000 mg and 2000 mg HFB30132A, the mean Cmax was 570.18 μg/mL and 898.65 μg/mL, the mean AUC0-t value was 644,749.42 h*μg/mL and 1,046,209.06 h*μg/mL, and the mean AUC0-∞ value was 806,127.47 h*μg/mL and 1,299,190.74 h*μg/mL, respectively. HFB30132A showed low clearance ranging from 1.38 to 1.59 mL/h, and a long terminal elimination half-life (t½) of 89–107 days. ADA test did not detect any anti-HFB30132A antibodiesConclusion: HFB30132A was safe and generally well-tolerated after single IV dose of 1,000 mg or 2000 mg in healthy Chinese adults. HFB30132A did not induce immunogenic response in this study. Our data support further clinical development of HFB30132A.Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT05275660.

【 授权许可】

Unknown   
Copyright © 2023 Li, Wu, Li, Cao, Wang, Chen, Li, He, Wu, Yang, Lin, Qiu, Liu, Zhou, Adrian, Schweizer, Zhang, Gu and Zhang.