PMID- 34229078
OWN - NLM
STAT- MEDLINE
DCOM- 20210812
LR  - 20210812
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 165
DP  - 2021 Oct 1
TI  - A randomized dose-escalation study on the safety, tolerability, immunogenicity, 
      pharmacokinetics and pharmacodynamics of a novel recombinant human albumin in 
      healthy subjects.
PG  - 105923
LID - S0928-0987(21)00224-4 [pii]
LID - 10.1016/j.ejps.2021.105923 [doi]
AB  - OBJECTIVE: Recombinant human albumin (rHA) is an alternative to human serum 
      albumin (HSA) for treating ascites in cirrhosis patients. This study was to 
      evaluate the safety, tolerability, immunogenicity, and 
      pharmacokinetics/pharmacodynamics (PK/PD) of rHA in healthy subjects to guide the 
      design for further clinical trials. METHODS: Healthy subjects aged 18-55 years 
      were enrolled in this double-blinded, first-in-human, placebo-controlled single 
      ascending dose (SAD) (1.25, 5, 10, 20, or 30g) and positive-controlled 
      multiple-dose study (3-day treatment of 10g/day for three cycles every three 
      weeks). The safety was assessed by adverse events (AEs). Antibodies (IgE and IgD) 
      and cytokines were analyzed for immunogenicity. Serum albumin levels and changes 
      in plasma colloid osmotic pressure (PCOP) and hematocrit (HCT) were measured for 
      PK/PD analysis. RESULTS: rHA was well tolerated as all AEs were assessed as mild 
      or moderate. No severe allergy or difference in the incidence of AEs was observed 
      among the different cohorts in the SAD study or in the different cycles in the 
      multiple-dose study. The incidence of AEs was similar for the rHA and HSA cohort. 
      Antibodies or cytokines showed no changes after drug administration. As expected, 
      serum albumin levels and PCOP increases, and HCT ratio decreases were 
      dose-related with significant differences (p < 0.01). No differences were 
      observed between rHA and HSA. CONCLUSION: rHA is safe and well-tolerated in 
      healthy Chinese subjects. rHA and HSA exhibited similar safety, tolerability, and 
      PK/PD profiles. The results support further evaluation of rHA treatment in 
      cirrhotic patients with ascites. The clinical trial registration numbers are 
      CTR20191221 
      (http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml).
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Li, Cuiyun
AU  - Li C
AD  - Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China. 
      Electronic address: lcy2442929@jlu.edu.cn.
FAU - Xiang, Wei
AU  - Xiang W
AD  - Tonghua Anrate Biopharmaceuticals Co., Ltd., Tonghua, Jilin, 134100, China. 
      Electronic address: xiang_wei@anrate.cn.
FAU - Wu, Min
AU  - Wu M
AD  - Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China. 
      Electronic address: wumin1987@jlu.edu.cn.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China. 
      Electronic address: zhanghong2015@jlu.edu.cn.
FAU - Cheng, Jianqiu
AU  - Cheng J
AD  - Tonghua Anrate Biopharmaceuticals Co., Ltd., Tonghua, Jilin, 134100, China. 
      Electronic address: cheng_jianqiu@anrate.cn.
FAU - Yang, Tao
AU  - Yang T
AD  - Tonghua Anrate Biopharmaceuticals Co., Ltd., Tonghua, Jilin, 134100, China. 
      Electronic address: yang_tao@anrate.cn.
FAU - Mai, Jiajia
AU  - Mai J
AD  - Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China. 
      Electronic address: 2272135673@qq.com.
FAU - Chi, Xiumei
AU  - Chi X
AD  - Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China. 
      Electronic address: chixm@jlu.edu.cn.
FAU - Gao, Xiuzhu
AU  - Gao X
AD  - Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China. 
      Electronic address: xiuzhugao@jlu.edu.cn.
FAU - Ding, Yanhua
AU  - Ding Y
AD  - Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China. 
      Electronic address: dingyanh@jlu.edu.cn.
FAU - Niu, Junqi
AU  - Niu J
AD  - Department of Hepatology, First Hospital, Jilin University, Changchun, 130021, 
      Jilin, China. Electronic address: junqiniu@jlu.edu.cn.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20210703
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - ZIF514RVZR (Serum Albumin, Human)
SB  - IM
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Healthy Volunteers
MH  - Humans
MH  - *Serum Albumin, Human
OTO - NOTNLM
OT  - Pharmacodynamics
OT  - Pharmacokinetics
OT  - Phase I study
OT  - Recombinant human albumin
OT  - Safety
EDAT- 2021/07/07 06:00
MHDA- 2021/08/13 06:00
CRDT- 2021/07/06 20:13
PHST- 2021/03/11 00:00 [received]
PHST- 2021/05/19 00:00 [revised]
PHST- 2021/06/28 00:00 [accepted]
PHST- 2021/07/07 06:00 [pubmed]
PHST- 2021/08/13 06:00 [medline]
PHST- 2021/07/06 20:13 [entrez]
AID - S0928-0987(21)00224-4 [pii]
AID - 10.1016/j.ejps.2021.105923 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2021 Oct 1;165:105923. doi: 10.1016/j.ejps.2021.105923. Epub 
      2021 Jul 3.