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This first\u2010in\u2010human trial evaluated the safety, tolerability, pharmacokinetics, and immunogenicity of potravitug, a novel fully human antibody against BKPyV. This partially randomized, single\u2010blinded, and placebo\u2010controlled trial enrolled 40 healthy participants randomized (3:1) to receive either single or multiple ascending doses (SAD\/MAD) of potravitug or placebo intravenously. In the SAD phase, 16 participants were enrolled in 4 cohorts (<jats:italic>n<\/jats:italic>\u2009=\u20094 each) with escalating doses of 100, 500, 1000, and 2000\u2009mg. In the MAD phase, 24 participants were enrolled in 3 consecutive cohorts (<jats:italic>n<\/jats:italic>\u2009=\u20098 each) with escalating doses of 500, 1000, and 2000\u2009mg administered four times at four\u2010week intervals. The primary outcome was incidence, frequency, and severity of treatment\u2010emergent adverse events (TEAEs). Secondary outcomes included pharmacokinetic parameters and incidence of anti\u2010drug antibodies. The ex\u00a0vivo neutralization capacity was an exploratory pharmacodynamic outcome. In SAD cohorts, 17 TEAEs occurred in 7 (58.3%) active and 3 in 2 (50.0%) placebo recipients. In MAD cohorts, 49 TEAEs occurred in 13 (72.2%) active and 21 in 5 (83.3%) placebo recipients. No dose\u2010limiting toxicities or anti\u2010drug antibodies were detected, indicating a favorable safety profile. Dose\u2010proportional increases in <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and AUC, with a half\u2010life characteristic of monoclonal antibodies, were observed. Based on pharmacokinetic\u2010pharmacodynamic modeling, a 1000\u2009mg intravenous dose administered four times at four\u2010week intervals is expected to maintain sufficient drug concentrations and receptor occupancy of VP1 (BKPyV major capsid protein) in both the blood and kidney for at least 1\u2009year.<\/jats:p>","DOI":"10.1111\/cts.70316","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T16:44:56Z","timestamp":1754930696000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First\u2010In\u2010Human, Randomized, Placebo\u2010Controlled, <scp>SAD<\/scp> and <scp>MAD<\/scp> Trial to Evaluate Safety, Tolerability, and <scp>PK<\/scp>\/<scp>PD<\/scp> Modeling of Potravitug in Healthy 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