{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:19:15Z","timestamp":1791631155696,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":19,"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":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Olamkicept selectively inhibits the cytokine interleukin\u20106 (IL\u20106) trans\u2010signaling pathway without blocking the classic pathway and is a promising immunoregulatory therapy for inflammatory bowel disease (IBD). These first\u2010in\u2010human, randomized, placebo\u2010controlled, single\u2010 (SAD) and multiple\u2010ascending dose (MAD) trials evaluated olamkicept safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics. Doses tested in the SAD trial included seven single intravenous doses (0.75, 7.5, 75, 150, 300, 600, and 750\u2009mg) and one subcutaneous (SC) dose (60\u2009mg) given to healthy subjects (<jats:italic>N<\/jats:italic>\u2009=\u200964), and three intravenous doses (75\u2009mg, 300\u2009mg, and 750\u2009mg) given to patients with Crohn's disease (CD; <jats:italic>N<\/jats:italic>\u2009=\u200924). Doses tested in the MAD trial included multiple intravenous doses (75, 300, and 600\u2009mg once weekly for 4\u2009weeks) given to healthy subjects (<jats:italic>N<\/jats:italic>\u2009=\u200924). No severe or serious treatment\u2010emergent adverse events (TEAEs) were recorded. The most common TEAEs were headache, nasopharyngitis, and myalgia in the SAD trial, and diarrhea, headache, and cough in the MAD trial. Infusion\u2010related reactions occurred in one and two subjects in the SAD and MAD trial, respectively, leading to treatment discontinuation in the MAD trial. Olamkicept showed dose\u2010independent pharmacokinetics after single and multiple administrations, and there was no major difference in systemic exposure between healthy subjects and patients with CD. Complete target engagement (inhibition of phosphorylation of signal transducer and activator of transcription\u20103) was achieved in blood around or above olamkicept serum concentrations of 1\u20135 \u03bcg\/mL. Overall, these results suggest that olamkicept is safe and well\u2010tolerated in healthy subjects and patients with CD after single intravenous\/SC and multiple intravenous administrations.<\/jats:p>","DOI":"10.1111\/cts.13832","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T05:48:31Z","timestamp":1716270511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Safety, tolerability, and pharmacokinetics of single\u2010 and multiple\u2010ascending doses of olamkicept: Results from randomized, placebo\u2010controlled, first\u2010in\u2010human phase I trials"],"prefix":"10.1111","volume":"17","author":[{"given":"Frank\u2010Dietrich","family":"Wagner","sequence":"first","affiliation":[{"name":"Charit\u00e9 Research Organisation  Berlin 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