Ying Wang, Yuanzhi Cheng, Yuhan Guo, Yang Fan, Renpeng Zhou, Qian Zhang, Ye Xu, Sheng Feng, Kai Shen, Wei Hu
{"title":"一项评估中国健康受试者在三个不同部位单次皮下注射Recaticimab的相对生物利用度、药效学和安全性的I期研究。","authors":"Ying Wang, Yuanzhi Cheng, Yuhan Guo, Yang Fan, Renpeng Zhou, Qian Zhang, Ye Xu, Sheng Feng, Kai Shen, Wei Hu","doi":"10.1007/s13318-025-00944-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Recaticimab (SHR-1209) is a humanized monoclonal antibody that binds to the proprotein convertase subtilisin/kexin type 9 (PCSK9) with high affinity. This study was conducted to compare the relative bioavailability, pharmacokinetics (PK), pharmacodynamics (PD), and safety of recaticimab following subcutaneous injection at three different sites in healthy Chinese subjects.</p><p><strong>Methods: </strong>In this randomized, parallel, open-label, phase I study, 159 healthy Chinese subjects were randomized to receive a single dose of 450 mg recaticimab subcutaneously into the abdomen, upper-arm, or thigh and were followed up until 113 days postdose. Adverse events were monitored, and serum samples were collected for PK, PD, and immunogenicity evaluation during the study.</p><p><strong>Results: </strong>The PK profiles of recaticimab were similar among different injection site groups. The geometric mean ratios of maximum serum concentration (C<sub>max</sub>), area under the serum concentration versus time curve (AUC) from time zero to the time of last quantifiable concentration (AUC<sub>0-last</sub>), and AUC from time zero extrapolated to infinity (AUC<sub>0-inf</sub>) between groups were all close to 1, with two-sided 90% confidence intervals within 0.8-1.25. Recaticimab showed similar effects on low-density lipoprotein cholesterol levels in all groups, with mean maximum percentage decreases ranging from 56.88% to 59.04%. The percentage changes from baseline in free PCSK9 and other lipid variables were similar across the three groups as well. Treatment-emergent adverse events were reported in 41/53 (77.4%, abdomen), 29/53 (54.7%, upper-arm), and 42/53 (79.2%, thigh) subjects, most of which were mild and resolved without treatment. The incidence of antidrug antibodies among the three groups was comparable.</p><p><strong>Conclusions: </strong>A single subcutaneous injection of 450 mg recaticimab into the abdomen, upper-arm, or thigh was well-tolerated and presented similar PK and PD profiles, which supported the interchangeable use of the three injection sites for patients.</p><p><strong>Clinical trial identifier: </strong>( www.</p><p><strong>Clinicaltrials: </strong>gov ) NCT05370950 2022-05-07.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":"265-272"},"PeriodicalIF":2.4000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Phase I Study to Evaluate the Relative Bioavailability, Pharmacodynamics, and Safety of a Single Subcutaneous Injection of Recaticimab at Three Different Sites in Healthy Chinese Subjects.\",\"authors\":\"Ying Wang, Yuanzhi Cheng, Yuhan Guo, Yang Fan, Renpeng Zhou, Qian Zhang, Ye Xu, Sheng Feng, Kai Shen, Wei Hu\",\"doi\":\"10.1007/s13318-025-00944-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>Recaticimab (SHR-1209) is a humanized monoclonal antibody that binds to the proprotein convertase subtilisin/kexin type 9 (PCSK9) with high affinity. This study was conducted to compare the relative bioavailability, pharmacokinetics (PK), pharmacodynamics (PD), and safety of recaticimab following subcutaneous injection at three different sites in healthy Chinese subjects.</p><p><strong>Methods: </strong>In this randomized, parallel, open-label, phase I study, 159 healthy Chinese subjects were randomized to receive a single dose of 450 mg recaticimab subcutaneously into the abdomen, upper-arm, or thigh and were followed up until 113 days postdose. Adverse events were monitored, and serum samples were collected for PK, PD, and immunogenicity evaluation during the study.</p><p><strong>Results: </strong>The PK profiles of recaticimab were similar among different injection site groups. The geometric mean ratios of maximum serum concentration (C<sub>max</sub>), area under the serum concentration versus time curve (AUC) from time zero to the time of last quantifiable concentration (AUC<sub>0-last</sub>), and AUC from time zero extrapolated to infinity (AUC<sub>0-inf</sub>) between groups were all close to 1, with two-sided 90% confidence intervals within 0.8-1.25. Recaticimab showed similar effects on low-density lipoprotein cholesterol levels in all groups, with mean maximum percentage decreases ranging from 56.88% to 59.04%. The percentage changes from baseline in free PCSK9 and other lipid variables were similar across the three groups as well. Treatment-emergent adverse events were reported in 41/53 (77.4%, abdomen), 29/53 (54.7%, upper-arm), and 42/53 (79.2%, thigh) subjects, most of which were mild and resolved without treatment. The incidence of antidrug antibodies among the three groups was comparable.</p><p><strong>Conclusions: </strong>A single subcutaneous injection of 450 mg recaticimab into the abdomen, upper-arm, or thigh was well-tolerated and presented similar PK and PD profiles, which supported the interchangeable use of the three injection sites for patients.</p><p><strong>Clinical trial identifier: </strong>( www.</p><p><strong>Clinicaltrials: </strong>gov ) NCT05370950 2022-05-07.</p>\",\"PeriodicalId\":11939,\"journal\":{\"name\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"volume\":\" \",\"pages\":\"265-272\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13318-025-00944-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Drug Metabolism and Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13318-025-00944-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
A Phase I Study to Evaluate the Relative Bioavailability, Pharmacodynamics, and Safety of a Single Subcutaneous Injection of Recaticimab at Three Different Sites in Healthy Chinese Subjects.
Background and objectives: Recaticimab (SHR-1209) is a humanized monoclonal antibody that binds to the proprotein convertase subtilisin/kexin type 9 (PCSK9) with high affinity. This study was conducted to compare the relative bioavailability, pharmacokinetics (PK), pharmacodynamics (PD), and safety of recaticimab following subcutaneous injection at three different sites in healthy Chinese subjects.
Methods: In this randomized, parallel, open-label, phase I study, 159 healthy Chinese subjects were randomized to receive a single dose of 450 mg recaticimab subcutaneously into the abdomen, upper-arm, or thigh and were followed up until 113 days postdose. Adverse events were monitored, and serum samples were collected for PK, PD, and immunogenicity evaluation during the study.
Results: The PK profiles of recaticimab were similar among different injection site groups. The geometric mean ratios of maximum serum concentration (Cmax), area under the serum concentration versus time curve (AUC) from time zero to the time of last quantifiable concentration (AUC0-last), and AUC from time zero extrapolated to infinity (AUC0-inf) between groups were all close to 1, with two-sided 90% confidence intervals within 0.8-1.25. Recaticimab showed similar effects on low-density lipoprotein cholesterol levels in all groups, with mean maximum percentage decreases ranging from 56.88% to 59.04%. The percentage changes from baseline in free PCSK9 and other lipid variables were similar across the three groups as well. Treatment-emergent adverse events were reported in 41/53 (77.4%, abdomen), 29/53 (54.7%, upper-arm), and 42/53 (79.2%, thigh) subjects, most of which were mild and resolved without treatment. The incidence of antidrug antibodies among the three groups was comparable.
Conclusions: A single subcutaneous injection of 450 mg recaticimab into the abdomen, upper-arm, or thigh was well-tolerated and presented similar PK and PD profiles, which supported the interchangeable use of the three injection sites for patients.
期刊介绍：
Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences.
Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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