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We performed two phase I, randomized, double\u2010blind, placebo\u2010controlled trials. In a single\u2010ascending dose trial, 40 healthy adults were randomized 3:1 to rademikibart (75\u2013600\u2009mg s.c., 300\u2009mg i.v.) or placebo, with 12\u2009weeks of follow\u2010up. In the multiple\u2010ascending dose trial, 31 adults with moderate\u2010to\u2010severe AD were randomized 4:1 to once weekly rademikibart (75\u2013300\u2009mg s.c.) or placebo for 4\u2009weeks, plus 7\u2009weeks of follow\u2010up. Most treatment\u2010emergent adverse events (TEAEs) were mild; none were serious. Two s.c. injection site reactions and one TEAE of conjunctivitis were reported, all were mild. Rapid and sustained improvements were observed in AD severity and in quality of life (QoL), without plateauing. At week 4, efficacy scores improved by a maximum of \u221274.4% (Eczema Area and Severity Index), \u221262.7% (body surface area), \u221252.8% (Pruritus Numerical Rating Scale [PNRS] severity), \u221254.4% (PNRS frequency), and\u2009\u2212\u200969.9% (Dermatology Life Quality Index). Thymus activation regulated chemokine inflammatory biomarker concentrations decreased in both trials (\u221255.4% in the pooled rademikibart arms vs. +18.0% with placebo, at week 5, in patients with AD). Exposure to rademikibart increased in a greater than dose\u2010proportional manner, suggesting nonlinear clearance. In summary, rademikibart was well\u2010tolerated and associated with rapid and sustained improvements in eczematous lesions, pruritus, QoL, and inflammatory biomarker concentrations during 4\u2009weeks of treatment. Efficacy responses did not plateau and were generally dose dependent. These promising findings support further development of rademikibart in patients with AD.<\/jats:p>","DOI":"10.1111\/cts.13656","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T06:43:45Z","timestamp":1697611425000},"page":"2614-2627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Rademikibart (<scp>CBP<\/scp>\u2010201), a next\u2010generation monoclonal antibody targeting human <scp>IL\u20104R\u03b1<\/scp>: Two phase I randomized trials, in healthy individuals and patients with atopic dermatitis"],"prefix":"10.1111","volume":"16","author":[{"given":"Junying","family":"Wang","sequence":"first","affiliation":[{"name":"Suzhou Connect Biopharmaceuticals  Taicang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery","family":"White","sequence":"additional","affiliation":[{"name":"Connect Biopharma  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Sansone","sequence":"additional","affiliation":[{"name":"Connect Biopharma  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7330-4713","authenticated-orcid":false,"given":"Lynda","family":"Spelman","sequence":"additional","affiliation":[{"name":"Veracity Clinical Research Pty Ltd.  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