PMID- 38157918
OWN - NLM
STAT- MEDLINE
DCOM- 20240219
LR  - 20240219
IS  - 1872-7913 (Electronic)
IS  - 0924-8579 (Linking)
VI  - 63
IP  - 2
DP  - 2024 Feb
TI  - A randomised, double-blind, placebo-controlled, first-in-human phase I study to 
      characterise the safety, pharmacokinetics and immunogenicity of 9MW1411 in 
      healthy Chinese subjects.
PG  - 107075
LID - S0924-8579(23)00364-3 [pii]
LID - 10.1016/j.ijantimicag.2023.107075 [doi]
AB  - INTRODUCTION: 9MW1411 is a humanised monoclonal antibody against Staphylococcus 
      aureus alpha-toxin. The safety, pharmacokinetics (PK) and immunogenicity of 
      9MW1411 should be characterised in humans before further clinical development. 
      METHODS: A single-centre, randomised, double-blind, placebo-controlled phase I 
      clinical study was conducted in humans for the first time. A total of 42 healthy 
      Chinese subjects were randomised to receive a single ascending dose of 9MW1411 
      (200, 600, 1500, 3000 or 5000 mg) or placebo. Safety, PK parameters and anti-drug 
      antibody (ADA) were analysed. Monte Carlo simulations (MCS) were performed to 
      predict the probability of target attainment (PTA) after single dose IV 
      administration of 1500, 3000 and 5000 mg of 9MW1411. RESULTS: Thirty-four 
      subjects received 9MW1411, completed the study and were included in data 
      analysis. Five cases of drug-related AEs occurred in four subjects. All the 
      adverse events (AEs) were mild or moderate. The C(max), AUC(0-t) and AUC(0-infinity) of 
      9MW1411 increased with dose after IV administration of 200 to 5000 mg 9MW1411. 
      The mean C(max) increased from 85.40 +/- 5.43 to 2082.11 +/- 343.10 microg/mL and 
      AUC(0-infinity) from 29,511.68 +/- 5550.91 to 729,985.49 +/- 124,932.18 h.microg/mL. The 
      elimination half-life (T(1/2)) was 19-23 days. 9MW1411 ADA was positive in three 
      subjects. MCS indicated that a single dose of 3000 or 5000 mg 9MW1411 could 
      achieve PTA > 90% for S. aureus. CONCLUSIONS: 9MW1411 has shown a good safety 
      profile in healthy Chinese subjects after a single dose up to 5000 mg. A single 
      dose of 3000 mg 9MW1411 is appropriate for use in subsequent studies.
CI  - Copyright (c) 2023. Published by Elsevier Ltd.
FAU - Yang, Haijing
AU  - Yang H
AD  - Phase Ⅰ Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health 
      Commission, Shanghai, China; National Clinical Research Center for Geriatric 
      Diseases (Huashan Hospital), Shanghai, China.
FAU - Wang, Peipei
AU  - Wang P
AD  - Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
FAU - Li, Xin
AU  - Li X
AD  - Key Laboratory of Clinical Pharmacology of Antibiotics, National Health 
      Commission, Shanghai, China; National Clinical Research Center for Geriatric 
      Diseases (Huashan Hospital), Shanghai, China; Institute of Antibiotics, Huashan 
      Hospital, Fudan University, Shanghai, China.
FAU - Wei, Qiong
AU  - Wei Q
AD  - Phase Ⅰ Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health 
      Commission, Shanghai, China; National Clinical Research Center for Geriatric 
      Diseases (Huashan Hospital), Shanghai, China.
FAU - Yu, Jicheng
AU  - Yu J
AD  - Phase Ⅰ Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health 
      Commission, Shanghai, China; National Clinical Research Center for Geriatric 
      Diseases (Huashan Hospital), Shanghai, China.
FAU - Wu, Xiaojie
AU  - Wu X
AD  - Phase Ⅰ Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health 
      Commission, Shanghai, China; National Clinical Research Center for Geriatric 
      Diseases (Huashan Hospital), Shanghai, China.
FAU - Huang, Ying
AU  - Huang Y
AD  - Key Laboratory of Clinical Pharmacology of Antibiotics, National Health 
      Commission, Shanghai, China; National Clinical Research Center for Geriatric 
      Diseases (Huashan Hospital), Shanghai, China; Nursing Department, Huashan 
      Hospital, Fudan University, Shanghai, China.
FAU - Li, Ruowan
AU  - Li R
AD  - Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
FAU - Du, Weijuan
AU  - Du W
AD  - Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
FAU - Zeng, Shaoqing
AU  - Zeng S
AD  - Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.
FAU - Wu, Hailan
AU  - Wu H
AD  - Key Laboratory of Clinical Pharmacology of Antibiotics, National Health 
      Commission, Shanghai, China; National Clinical Research Center for Geriatric 
      Diseases (Huashan Hospital), Shanghai, China; Institute of Antibiotics, Huashan 
      Hospital, Fudan University, Shanghai, China.
FAU - Wang, Shuhai
AU  - Wang S
AD  - Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China. Electronic address: 
      shuhai.wang@mabwell.com.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Phase Ⅰ Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health 
      Commission, Shanghai, China; National Clinical Research Center for Geriatric 
      Diseases (Huashan Hospital), Shanghai, China; Institute of Antibiotics, Huashan 
      Hospital, Fudan University, Shanghai, China. Electronic address: 
      zhangj_fudan@aliyun.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20231227
PL  - Netherlands
TA  - Int J Antimicrob Agents
JT  - International journal of antimicrobial agents
JID - 9111860
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Humans
MH  - *Staphylococcus aureus
MH  - *Antibodies, Monoclonal, Humanized/adverse effects
MH  - Double-Blind Method
MH  - Healthy Volunteers
MH  - China
MH  - Area Under Curve
OTO - NOTNLM
OT  - 9mw1411
OT  - Alpha toxin
OT  - First-in-human study
OT  - Monoclonal antibody
OT  - Pharmacokinetics
OT  - Staphylococcus aureus
EDAT- 2024/01/02 11:43
MHDA- 2024/02/19 06:42
CRDT- 2023/12/29 19:12
PHST- 2023/07/09 00:00 [received]
PHST- 2023/12/16 00:00 [revised]
PHST- 2023/12/21 00:00 [accepted]
PHST- 2024/02/19 06:42 [medline]
PHST- 2024/01/02 11:43 [pubmed]
PHST- 2023/12/29 19:12 [entrez]
AID - S0924-8579(23)00364-3 [pii]
AID - 10.1016/j.ijantimicag.2023.107075 [doi]
PST - ppublish
SO  - Int J Antimicrob Agents. 2024 Feb;63(2):107075. doi: 
      10.1016/j.ijantimicag.2023.107075. Epub 2023 Dec 27.