Willis, Brian A.Lo, Albert C.Dage, Jeffrey L.Shcherbinin, SergeyChinchen, LouiseAndersen, Scott W.LaBell, Elizabeth S.Perahia, David G. S.Hauck, Paula M.Lowe, Stephen L.2024-03-282024-03-282023-09-15Willis BA, Lo AC, Dage JL, et al. Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial. J Alzheimers Dis Rep. 2023;7(1):1015-1024. Published 2023 Sep 15. doi:10.3233/ADR-230012https://hdl.handle.net/1805/39569Background: Zagotenemab (LY3303560), a monoclonal antibody, preferentially binds to extracellular, misfolded, aggregated tau that has been implicated in Alzheimer's disease (AD). Objective: The goal of this study was to assess the safety and pharmacokinetics of multiple doses of zagotenemab in participants with AD. Methods: This was a Phase Ib, multi-site, participant- and investigator-blind, placebo-controlled, parallel-group study in participants with mild cognitive impairment due to AD or mild to moderate AD. After screening, participants were randomized to zagotenemab 70 mg, 210 mg, or placebo every 4 weeks for up to 49 weeks and were followed up for 16 weeks. Results: A total of 13 males and 9 females, aged 59 to 84 years, were dosed. No deaths occurred during this study. A total of 4 serious adverse events occurred in 2 participants who then discontinued the study. The most commonly reported (3 or more participants) treatment-emergent adverse events were sinus bradycardia, headache, fall, and bronchitis. The pharmacokinetics profile showed generally linear exposures across the dose range studied with a clearance of ~8 mL/h. The half-life of zagotenemab in serum was ~20 days. A dose-dependent increase in plasma tau was observed. No other significant pharmacodynamic differences were observed due to low dose levels and limited treatment duration. Conclusions: No dose-limiting adverse events were observed with zagotenemab treatment. Pharmacokinetics of zagotenemab were typical for a monoclonal antibody. Meaningful pharmacodynamic differences were not observed.en-USAttribution-NonCommercial 4.0 InternationalAggregated tauAlzheimer’s diseaseAntibodySafety pharmacokineticsZagotenemabArticle