{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:41:57Z","timestamp":1792676517713,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Toll\u2010like receptor (TLR)7 is a pattern recognition receptor that critically contributes to the pathogenesis of systemic lupus erythematosus (SLE). DS\u20107011a is an anti\u2010TLR7 monoclonal antibody that prevents TLR7 from signaling. The aim of this first\u2010in\u2010human, double\u2010blind, randomized, and placebo\u2010controlled study was to evaluate the safety, pharmacokinetics, immunogenicity, and pharmacodynamics of single ascending intravenous (IV) and subcutaneous (SC) doses of DS\u20107011a in healthy subjects (HS) (NCT05203692). On day 1, 80 HS received DS\u20107011a or placebo 6:2 in 10 cohorts (7 treated IV and 3 SC) of 8 each and were followed for 8 weeks until day 57. Safety was evaluated by recording treatment\u2010emergent adverse events (TEAEs), pharmacokinetics by measuring plasma DS\u20107011a, immunogenicity by measuring plasma anti\u2010drug antibodies (ADAs), and pharmacodynamics by evaluating the suppression of interleukin\u20106 production ex vivo in whole blood. DS\u20107011a was safe and well tolerated across all cohorts. TEAEs were mostly mild in severity and not drug\u2010related. DS\u20107011a exposure increased with the dose but was not dose proportional, as the elimination of lower doses was accelerated by target\u2010mediated drug disposition. Terminal half\u2010life was about 15\u201017 days and T<jats:sub>max<\/jats:sub> upon SC administration was about 5 days. DS\u20107011a induced ADAs in about half of HS but with no impact on clinical findings and pharmacokinetics. Pharmacodynamic (PD) response also increased with the dose and at the higher doses was of large extent (&gt;90%), early onset, and lasting duration. DS\u20107011a showed favorable safety, pharmacokinetics, immunogenicity, and PD properties that support its development for the treatment of SLE.<\/jats:p>","DOI":"10.1002\/jcph.6117","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T11:41:31Z","timestamp":1724326891000},"page":"41-52","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["First\u2010in\u2010Human Study of the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of DS\u20107011a, an Anti\u2010TLR7 Antagonistic Monoclonal Antibody for the Treatment of Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"65","author":[{"given":"Giorgio","family":"Senaldi","sequence":"first","affiliation":[{"name":"Daiichi Sankyo Basking Ridge NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Mohan","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo 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