Dataset Information

Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial.

ABSTRACT:

Background

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.Clinicaltrials.gov: NCT03019536.

SUBMITTER: Willis BA

PROVIDER: S-EPMC10578324 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial.

Willis Brian A BA Lo Albert C AC Dage Jeffrey L JL Shcherbinin Sergey S Chinchen Louise L Andersen Scott W SW LaBell Elizabeth S ES Perahia David G S DGS Hauck Paula M PM Lowe Stephen L SL

Journal of Alzheimer's disease reports 20230915 1

<h4>Background</h4>Zagotenemab (LY3303560), a monoclonal antibody, preferentially binds to extracellular, misfolded, aggregated tau that has been implicated in Alzheimer's disease (AD).<h4>Objective</h4>The goal of this study was to assess the safety and pharmacokinetics of multiple doses of zagotenemab in participants with AD.<h4>Methods</h4>This was a Phase Ib, multi-site, participant- and investigator-blind, placebo-controlled, parallel-group study in participants with mild cognitive impairme ...[more]

PMID: 37849628

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Dataset Information

Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial.

Background

Objective

Methods

Results

Conclusions

Publications

Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial.

Similar Datasets

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