A randomized dose-escalation study on the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of a novel recombinant human albumin in healthy subjects
Copyright © 2021. Published by Elsevier B.V..
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).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:165 |
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| Enthalten in: |
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences - 165(2021) vom: 01. Okt., Seite 105923 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Cuiyun [VerfasserIn] |
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| Links: |
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| Themen: |
Clinical Trial, Phase I |
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| Anmerkungen: |
Date Completed 12.08.2021 Date Revised 12.08.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejps.2021.105923 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM327753943 |
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| 041 | |a eng | ||
| 100 | 1 | |a Li, Cuiyun |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A randomized dose-escalation study on the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of a novel recombinant human albumin in healthy subjects |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 12.08.2021 | ||
| 500 | |a Date Revised 12.08.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021. Published by Elsevier B.V. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Pharmacodynamics | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Phase I study | |
| 650 | 4 | |a Recombinant human albumin | |
| 650 | 4 | |a Safety | |
| 650 | 7 | |a Serum Albumin, Human |2 NLM | |
| 650 | 7 | |a ZIF514RVZR |2 NLM | |
| 700 | 1 | |a Xiang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Jianqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Mai, Jiajia |e verfasserin |4 aut | |
| 700 | 1 | |a Chi, Xiumei |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Xiuzhu |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yanhua |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Junqi |e verfasserin |4 aut | |
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