Shan Jing, Yu Zhang, Yang Lin, Xiaowen Gu, Jing Liu, Antonio Guglietta, Jan Noukens, Tonke Van Bragt, Lina Wang, Jiajia Chen, Harald Reinhart, Xia Pu
{"title":"健康中国人静脉注射埃加替莫德和皮下注射埃加替莫德 PH20 的药代动力学、药效学和安全性。","authors":"Shan Jing, Yu Zhang, Yang Lin, Xiaowen Gu, Jing Liu, Antonio Guglietta, Jan Noukens, Tonke Van Bragt, Lina Wang, Jiajia Chen, Harald Reinhart, Xia Pu","doi":"10.1007/s40268-024-00490-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and China for the treatment of gMG.</p><p><strong>Objective: </strong>We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants.</p><p><strong>Methods: </strong>In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters.</p><p><strong>Results: </strong>After the fourth IV infusion, a mean maximum observed concentration (C<sub>max</sub>) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC<sub>0-168h</sub>) was 5300 µg × h/mL. After the fourth SC injection, a mean C<sub>max</sub> of 42.1 µg/mL was achieved with a median T<sub>max</sub> of 47.74 h; the mean AUC<sub>0-168h</sub> was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study.</p><p><strong>Conclusions: </strong>The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage.</p><p><strong>Clinical trial registration: </strong>CTR20211952 and CTR20211805.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics, Pharmacodynamics, and Safety of Intravenous Efgartigimod and Subcutaneous Efgartigimod PH20 in Healthy Chinese Participants.\",\"authors\":\"Shan Jing, Yu Zhang, Yang Lin, Xiaowen Gu, Jing Liu, Antonio Guglietta, Jan Noukens, Tonke Van Bragt, Lina Wang, Jiajia Chen, Harald Reinhart, Xia Pu\",\"doi\":\"10.1007/s40268-024-00490-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and China for the treatment of gMG.</p><p><strong>Objective: </strong>We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants.</p><p><strong>Methods: </strong>In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters.</p><p><strong>Results: </strong>After the fourth IV infusion, a mean maximum observed concentration (C<sub>max</sub>) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC<sub>0-168h</sub>) was 5300 µg × h/mL. After the fourth SC injection, a mean C<sub>max</sub> of 42.1 µg/mL was achieved with a median T<sub>max</sub> of 47.74 h; the mean AUC<sub>0-168h</sub> was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study.</p><p><strong>Conclusions: </strong>The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. 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Pharmacokinetics, Pharmacodynamics, and Safety of Intravenous Efgartigimod and Subcutaneous Efgartigimod PH20 in Healthy Chinese Participants.
Background: Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and China for the treatment of gMG.
Objective: We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants.
Methods: In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters.
Results: After the fourth IV infusion, a mean maximum observed concentration (Cmax) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC0-168h) was 5300 µg × h/mL. After the fourth SC injection, a mean Cmax of 42.1 µg/mL was achieved with a median Tmax of 47.74 h; the mean AUC0-168h was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study.
Conclusions: The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage.
Clinical trial registration: CTR20211952 and CTR20211805.
期刊介绍：
Drugs in R&D is an international, peer reviewed, open access, online only journal, and provides timely information from all phases of drug research and development that will inform clinical practice. Healthcare decision makers are thus provided with knowledge about the developing place of a drug in therapy.
The Journal includes:
Clinical research on new and established drugs;
Preclinical research of direct relevance to clinical drug development;
Short communications and case study reports that meet the above criteria will also be considered;
Reviews may also be considered.
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