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This first\u2010in\u2010human, phase I, randomized, double\u2010blind, placebo\u2010controlled study (NCT03096795) evaluated the safety, tolerability, pharmacokinetics (PKs), immunogenicity, target engagement, and pharmacodynamics (PDs) of tozorakimab. This was a 3\u2010part study. In part 1, 56 healthy participants with a history of mild atopy received single escalating doses of either intravenous or subcutaneous tozorakimab or placebo. In part 2, 24 patients with mild COPD received multiple ascending doses of subcutaneous tozorakimab or placebo. In part 3, 8 healthy Japanese participants received a single intravenous dose of tozorakimab or placebo. The safety data collected included treatment\u2010emergent adverse events (TEAEs), vital signs, and clinical laboratory parameters. Biological samples for PKs, immunogenicity, target engagement, and PD biomarker analyses were collected. No meaningful differences in the frequencies of TEAEs were observed between the tozorakimab and placebo arms. Three tozorakimab\u2010treated participants with COPD experienced treatment\u2010emergent serious adverse events. Subcutaneous or intravenous tozorakimab demonstrated linear, time\u2010independent PKs with a mean half\u2010life of 11.7\u201317.3\u2009days. Treatment\u2010emergent anti\u2010drug antibody frequency was low. Engagement of tozorakimab with endogenous IL\u201033 in serum and nasal airways was demonstrated. Tozorakimab significantly reduced serum IL\u20105 and IL\u201013 levels in patients with COPD compared with placebo. Overall, tozorakimab was well tolerated, with a linear, time\u2010independent serum PK profile. Additionally, biomarker studies demonstrated proof of mechanism. Overall, these data support the further clinical development of tozorakimab in COPD and other inflammatory diseases.<\/jats:p>","DOI":"10.1002\/cpt.3147","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:16:11Z","timestamp":1703031371000},"page":"565-575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["A Randomized Phase I Study of the Anti\u2010Interleukin\u201033 Antibody Tozorakimab in Healthy Adults and Patients With Chronic Obstructive Pulmonary Disease"],"prefix":"10.1002","volume":"115","author":[{"given":"Fred","family":"Reid","sequence":"first","affiliation":[{"name":"Clinical Development, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&amp;D AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Unit 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