PMID- 36147329
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220924
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - 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.
PG  - 983505
LID - 10.3389/fphar.2022.983505 [doi]
LID - 983505
AB  - 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.
CI  - Copyright (c) 2022 Hao, Zhang, Ma, Cheng, Ji, Liu, Zhao, Zhang, Li, Yan, Margolis, 
      Zhu, Zhang and Zhang.
FAU - Hao, Xiaohua
AU  - Hao X
AD  - Beijing Ditan Hospital, Capital Medical University, Beijing, China.
FAU - Zhang, Zheng
AU  - Zhang Z
AD  - 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.
FAU - Ma, Ji
AU  - Ma J
AD  - Brii Biosciences Inc, Durham, NC, United States.
FAU - Cheng, Lin
AU  - Cheng L
AD  - 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.
FAU - Ji, Yun
AU  - Ji Y
AD  - Brii Biosciences Inc, Durham, NC, United States.
FAU - Liu, Yang
AU  - Liu Y
AD  - Brii Biosciences Inc, Durham, NC, United States.
FAU - Zhao, Dong
AU  - Zhao D
AD  - Beijing Ditan Hospital, Capital Medical University, Beijing, China.
FAU - Zhang, Wen
AU  - Zhang W
AD  - Beijing Ditan Hospital, Capital Medical University, Beijing, China.
FAU - Li, Chunming
AU  - Li C
AD  - Brii Biosciences Inc, Durham, NC, United States.
FAU - Yan, Li
AU  - Yan L
AD  - Brii Biosciences Inc, Durham, NC, United States.
FAU - Margolis, David
AU  - Margolis D
AD  - Brii Biosciences Inc, Durham, NC, United States.
FAU - Zhu, Qing
AU  - Zhu Q
AD  - Brii Biosciences Inc, Durham, NC, United States.
FAU - Zhang, Yao
AU  - Zhang Y
AD  - TSB Therapeutics, Beijing, China.
FAU - Zhang, Fujie
AU  - Zhang F
AD  - Beijing Ditan Hospital, Capital Medical University, Beijing, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT04479644
SI  - ClinicalTrials.gov/NCT04691180
SI  - ClinicalTrials.gov/NCT04479631
PT  - Journal Article
DEP - 20220906
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9486188
OTO - NOTNLM
OT  - SARS-CoV-2
OT  - extended half-life
OT  - monoclonal antibody
OT  - neutralizing activity
OT  - pharmacokinetics
OT  - safety
COIS- Author YZ is employed by TSB Therapeutics (Beijing) Co. Ltd. and authors JM, YJ, 
      CL, YL, LY, DM, and QZ are employed by Brii Biosciences INC., Durham, NC, United 
      States. The remaining authors declare that the research was conducted in the 
      absence of any commercial or financial relationships that could be construed as a 
      potential conflict of interest. This study received funding from TSB Therapeutics 
      (Beijing) Co. Ltd. and Brii Biosciences INC., Durham, NC, United States. The 
      funder had the following involvement with the study: study design, data 
      collection and analysis, decision to publish, and preparation of the manuscript.
EDAT- 2022/09/24 06:00
MHDA- 2022/09/24 06:01
PMCR- 2022/09/06
CRDT- 2022/09/23 02:38
PHST- 2022/07/01 00:00 [received]
PHST- 2022/08/17 00:00 [accepted]
PHST- 2022/09/23 02:38 [entrez]
PHST- 2022/09/24 06:00 [pubmed]
PHST- 2022/09/24 06:01 [medline]
PHST- 2022/09/06 00:00 [pmc-release]
AID - 983505 [pii]
AID - 10.3389/fphar.2022.983505 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Sep 6;13:983505. doi: 10.3389/fphar.2022.983505. 
      eCollection 2022.