Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial
Background: Passive immune agents play an important role in the prevention of rabies following exposure. This trial investigated the safety, tolerability, and pharmacokinetics of recombinant human monoclonal antibodies against rabies virus (rhRIG). Method: This clinical trial was conducted on health...
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ftdoajarticles:oai:doaj.org/article:cafd13263f104736abc1f3ffa3de34a1 2023-11-12T04:13:45+01:00 Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial Xi Chen Jin Duan Yufeng Li Qinghua Zhao Yu Zhao Lan Yu Xiaona Li Huixin Wang 2023-09-01T00:00:00Z https://doi.org/10.1016/j.tmaid.2023.102645 https://doaj.org/article/cafd13263f104736abc1f3ffa3de34a1 EN eng Elsevier http://www.sciencedirect.com/science/article/pii/S1477893923001059 https://doaj.org/toc/1873-0442 1873-0442 doi:10.1016/j.tmaid.2023.102645 https://doaj.org/article/cafd13263f104736abc1f3ffa3de34a1 Travel Medicine and Infectious Disease, Vol 55, Iss , Pp 102645- (2023) Ormutivimab Anti-rabies monoclonal antibody Pharmacokinetics properties Tolerability Neutralizing antibody levels Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2023 ftdoajarticles https://doi.org/10.1016/j.tmaid.2023.102645 2023-10-15T00:35:57Z Background: Passive immune agents play an important role in the prevention of rabies following exposure. This trial investigated the safety, tolerability, and pharmacokinetics of recombinant human monoclonal antibodies against rabies virus (rhRIG). Method: This clinical trial was conducted on healthy Chinese adults. The subjects were enrolled into three dosage groups. The safety of the drug was assessed, and the blood concentration of the monoclonal antibody (NM57) and the neutralizing antibody levels were measured. Results: The rhRIG presented favorable safety and tolerability.The subjects in the low(10 IU/kg), medium(20 IU/kg), and high(40 IU/kg) dosage groups reported the Cmax of 87.15 ± 18.86, 210.92 ± 77.5, and 394.11 ± 134.98 ng/ml, respectively, and the AUC0-t of 2115.8 ± 791.3, 6064 ± 1890, and 10735.6 ± 4090 ng/mL*d, and the T1/2 z of 15.82 ± 3.03, 15.96 ± 2.37, and 14.34 ± 3.84 d. The Tmax of neutralizing antibody levels in the serum was about 10d (5-14d). The detectable rate of neutralizing antibody levels in the medium dosage group was close to that in the high dosage group and higher than that in the low dosage group. Conclusions: The 10–40IU/kg rhRIG was well tolerated by the participants. The results of the pharmacokinetic analysis were consistent with the characteristics of linear elimination. The neutralizing antibody levels was positively correlated with the dosage of rhRIG. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Travel Medicine and Infectious Disease 55 102645 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Ormutivimab Anti-rabies monoclonal antibody Pharmacokinetics properties Tolerability Neutralizing antibody levels Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Ormutivimab Anti-rabies monoclonal antibody Pharmacokinetics properties Tolerability Neutralizing antibody levels Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Xi Chen Jin Duan Yufeng Li Qinghua Zhao Yu Zhao Lan Yu Xiaona Li Huixin Wang Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial |
topic_facet |
Ormutivimab Anti-rabies monoclonal antibody Pharmacokinetics properties Tolerability Neutralizing antibody levels Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Background: Passive immune agents play an important role in the prevention of rabies following exposure. This trial investigated the safety, tolerability, and pharmacokinetics of recombinant human monoclonal antibodies against rabies virus (rhRIG). Method: This clinical trial was conducted on healthy Chinese adults. The subjects were enrolled into three dosage groups. The safety of the drug was assessed, and the blood concentration of the monoclonal antibody (NM57) and the neutralizing antibody levels were measured. Results: The rhRIG presented favorable safety and tolerability.The subjects in the low(10 IU/kg), medium(20 IU/kg), and high(40 IU/kg) dosage groups reported the Cmax of 87.15 ± 18.86, 210.92 ± 77.5, and 394.11 ± 134.98 ng/ml, respectively, and the AUC0-t of 2115.8 ± 791.3, 6064 ± 1890, and 10735.6 ± 4090 ng/mL*d, and the T1/2 z of 15.82 ± 3.03, 15.96 ± 2.37, and 14.34 ± 3.84 d. The Tmax of neutralizing antibody levels in the serum was about 10d (5-14d). The detectable rate of neutralizing antibody levels in the medium dosage group was close to that in the high dosage group and higher than that in the low dosage group. Conclusions: The 10–40IU/kg rhRIG was well tolerated by the participants. The results of the pharmacokinetic analysis were consistent with the characteristics of linear elimination. The neutralizing antibody levels was positively correlated with the dosage of rhRIG. |
format |
Article in Journal/Newspaper |
author |
Xi Chen Jin Duan Yufeng Li Qinghua Zhao Yu Zhao Lan Yu Xiaona Li Huixin Wang |
author_facet |
Xi Chen Jin Duan Yufeng Li Qinghua Zhao Yu Zhao Lan Yu Xiaona Li Huixin Wang |
author_sort |
Xi Chen |
title |
Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial |
title_short |
Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial |
title_full |
Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial |
title_fullStr |
Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial |
title_full_unstemmed |
Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial |
title_sort |
pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhrig) in chinese healthy population: a randomized, single-blinded, placebo-controlled phase ia clinical trial |
publisher |
Elsevier |
publishDate |
2023 |
url |
https://doi.org/10.1016/j.tmaid.2023.102645 https://doaj.org/article/cafd13263f104736abc1f3ffa3de34a1 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Travel Medicine and Infectious Disease, Vol 55, Iss , Pp 102645- (2023) |
op_relation |
http://www.sciencedirect.com/science/article/pii/S1477893923001059 https://doaj.org/toc/1873-0442 1873-0442 doi:10.1016/j.tmaid.2023.102645 https://doaj.org/article/cafd13263f104736abc1f3ffa3de34a1 |
op_doi |
https://doi.org/10.1016/j.tmaid.2023.102645 |
container_title |
Travel Medicine and Infectious Disease |
container_volume |
55 |
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102645 |
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1782331604362854400 |