Antimicrob Agents Chemother . Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab in Chinese Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Phase 1 Study

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Antimicrob Agents Chemother


. 2021 May 10;AAC.00350-21.
doi: 10.1128/AAC.00350-21. Online ahead of print.
Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab in Chinese Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Phase 1 Study


Xiaojie Wu ¹ , Nanyang Li ¹ , Guoqin Wang ² , Wei Liu ² , Jicheng Yu ¹ , Guoying Cao ¹ , Jingjing Wang ¹ , Yuancheng Chen ¹ , Juan Ma ² , Jufang Wu ¹ , Haijing Yang ¹ , Xiaomeng Mao ¹ , Jinjie He ¹ , Yiqi Yu ³ , Chao Qiu ³ , Ning Li ² , Sheng Yao ² , Hui Feng ² , Jinghua Yan ⁴ , Wenhong Zhang ⁵ , Jing Zhang ^{6 7}



Affiliations

• PMID: 33972256
• DOI: 10.1128/AAC.00350-21

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479 or LY-CoV016), in healthy adults. This paper involves a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or a placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose ^{increased from 2.5 to 50 mg/kg. The} elimination half-life ^{(t1/2) value did not differ among different dose} cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).