中文版 | English
Title

Randomized, placebo-controlled, single-blind phase 1 studies of the safety, tolerability, and pharmacokinetics of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies with an extended half-life in healthy adults

Author
Corresponding AuthorZhang,Yao; Zhang,Fujie
Publication Years
2022-09-06
DOI
Source Title
EISSN
1663-9812
Volume13
Abstract
Background: BRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies as a cocktail therapy for treating COVID-19 with a modified Fc region that extends half-life. Methods: Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in first-in-human, placebo-controlled, single ascending dose phase 1 studies in healthy adults. 44 participants received a single intravenous infusion of single BRII-196 or BRII-198 up to 3,000 mg, or BRII-196 and BRII-198 combination up to 1500/1500 mg, or placebo and were followed up for 180 days. Primary endpoints were incidence of adverse events (AEs) and changes from pre-dose baseline in clinical assessments. Secondary endpoints included pharmacokinetics profiles of BRII-196/BRII-198 and detection of anti-drug antibodies (ADAs). Plasma neutralization activities against SARS-CoV-2 Delta live virus in comparison to post-vaccination plasma were evaluated as exploratory endpoints. Results: All infusions were well-tolerated without systemic or local infusion reactions, dose-limiting AEs, serious AEs, or deaths. Most treatment-emergent AEs were isolated asymptomatic laboratory abnormalities of grade 1-2 in severity. BRII-196 and BRII-198 displayed pharmacokinetics characteristic of Fc-engineered human IgG1 with mean terminal half-lives of 44.6–48.6 days and 72.2–83.0 days, respectively, with no evidence of interaction or significant anti-drug antibody development. Neutralizing activities against the live virus of the SARS-CoV-2 Delta variant were maintained in plasma samples taken on day 180 post-infusion. Conclusion: BRII-196 and BRII-198 are safe, well-tolerated, and suitable therapeutic or prophylactic options for SARS-CoV-2 infection. Clinical Trial Registration: ClinicalTrials.gov under identifiers NCT04479631, NCT04479644, and NCT04691180.
Keywords
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
Others
Funding Project
[2020YFC0861200] ; [2021YFC0864500] ; [JSGG20200207155251653] ; [JSGG20200807171401008]
WOS Research Area
Pharmacology & Pharmacy
WOS Subject
Pharmacology & Pharmacy
WOS Accession No
WOS:000863764700001
Publisher
Scopus EID
2-s2.0-85138340031
Data Source
Scopus
Citation statistics
Cited Times [WOS]:2
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/402702
DepartmentSchool of Medicine
南方科技大学第二附属医院
Affiliation
1.Beijing Ditan Hospital,Capital Medical University,Beijing,China
2.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People’s Hospital,The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,China
3.Brii Biosciences Inc,Durham,United States
4.TSB Therapeutics,Beijing,China
Recommended Citation
GB/T 7714
Hao,Xiaohua,Zhang,Zheng,Ma,Ji,et al. Randomized, placebo-controlled, single-blind phase 1 studies of the safety, tolerability, and pharmacokinetics of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies with an extended half-life in healthy adults[J]. Frontiers in Pharmacology,2022,13.
APA
Hao,Xiaohua.,Zhang,Zheng.,Ma,Ji.,Cheng,Lin.,Ji,Yun.,...&Zhang,Fujie.(2022).Randomized, placebo-controlled, single-blind phase 1 studies of the safety, tolerability, and pharmacokinetics of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies with an extended half-life in healthy adults.Frontiers in Pharmacology,13.
MLA
Hao,Xiaohua,et al."Randomized, placebo-controlled, single-blind phase 1 studies of the safety, tolerability, and pharmacokinetics of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies with an extended half-life in healthy adults".Frontiers in Pharmacology 13(2022).
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