{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:01:46Z","timestamp":1794045706792,"version":"4.8.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Recombinant human interleukin\u20107 hybrid Fc (rhIL\u20107\u2010hyFc) is a homodimer of rhIL\u20107 fused to a hyFc. Exogenous IL\u20107 promotes T cell proliferation and increases lymphocyte count, making it a potential treatment option for lymphopenia and cancer. To improve therapeutic efficacy, rhIL\u20107\u2010hyFc was developed as a long\u2010acting IL\u20107. This study aimed to create a pharmacokinetic model for rhIL\u20107\u2010hyFc by incorporating neonatal Fc receptor (FcRn)\u2010mediated recycling and target\u2010mediated drug disposition (TMDD) of the IL\u20107 receptor. Data were collected from a randomized, double\u2010blind, placebo\u2010controlled phase 1 trial involving 30 healthy volunteers who received single doses of rhIL\u20107\u2010hyFc. Volunteers received 20 or 60\u2009mg\/kg subcutaneously, 60\u2009mg\/kg intramuscularly (IM), or a placebo. Clinical data were provided by Genexine Inc. (Seoul, Republic of Korea). A TMDD\u2010FcRn\u2013mediated recycling pharmacokinetic model was developed using NONMEM 7.5 software, assisted by PsN 5.3.1 software. A quasi\u2010steady\u2010state approximation was used to describe drug\u2010receptor and drug\u2010FcRn interactions. The model evaluation included goodness of fit, visual predictive checks, and bootstrap analysis. Based on the pharmacokinetic parameters of the final model, a simulation was conducted to select the dosage regimen, ensuring a probability of at least 0.8 for meeting both safety and efficacy criteria. The model successfully described the pharmacokinetic profiles of 24 patients administered rhIL\u20107\u2010hyFc. Based on the simulation results, 670\u2013800\u2009\u03bcg\/kg every 3\u2009weeks, 1010\u20131530\u2009\u03bcg\/kg every 6\u2009weeks, and 1510\u20132190\u2009\u03bcg\/kg every 9\u2009weeks IM were proposed. These results may help further understand rhIL\u20107\u2010hyFc characteristics and, moreover, provide guidance for selecting the appropriate dosing regimen in future clinical trials.<\/jats:p>","DOI":"10.1111\/cts.70252","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T10:39:59Z","timestamp":1747823999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dose Optimization of <scp>rhIL<\/scp>\u20107\u2010<scp>hyFc<\/scp> for Patients With Lymphopenia Using a Neonatal Fc Receptor\u2010Mediated Recycling\u2010Based and Target\u2010Mediated Drug Disposition Pharmacokinetic Model"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4175-4189","authenticated-orcid":false,"given":"Hye Seon","family":"Jeon","sequence":"first","affiliation":[{"name":"College of Pharmacy Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Hanyang University, College of Medicine  Seoul Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics Hanyang University Seoul Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-597X","authenticated-orcid":false,"given":"Woojin","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heeyoon","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungnam National University  Daejeon Republic of Korea"},{"name":"Population Health Sciences Program, Department of Population and Quantitative Health Sciences University of Massachusetts Chan Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Research Institute of NeoImmuneTech, Inc.  Pohang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u2010Sun","family":"Byun","sequence":"additional","affiliation":[{"name":"Clinical Development Department Genexine, Inc.  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Neoimmunetech Website https:\/\/www.neoimmunetech.com\/science\/publications."},{"key":"e_1_2_8_7_1","unstructured":"J.Sohn G. M.Kim K. 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Neoimmunetech Website \u201dhttps:\/\/www.neoimmunetech.com\/science\/publications."},{"key":"e_1_2_8_23_1","unstructured":"B. R.Gastman G.Ansstas P.Funchain et\u00a0al. \u201cA Phase 1b\/2a Study of Safety and Efficacy of NT\u2010I7 in Combination With Anti\u2010PD\u2010L1 (Atezolizumab) in Patients With Anti\u2010PD\u20101\/PD\u2010L1 Na\u00efve or Relapsed\/Refractory (R\/R) High\u2010Risk Skin Cancers: The Phase 1b Report. Poster Presented at ASCO. Neoimmunetech Website \u201dhttps:\/\/www.neoimmunetech.com\/science\/publications."},{"key":"e_1_2_8_24_1","unstructured":"A.Naing J.Fan B. H.Lee et\u00a0al. \u201cSafety Pharmacokinetics Pharmacodynamics Profiles and Preliminary Antitumor Activity of Phase 1b\/2a Study of NT\u2010I7 a Long\u2010Acting Interleukin\u20107 Plus Pembrolizumab in Patients With Advanced Solid Tumors: The Phase 1b Data Report. Neoimmunetech Website. 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