This multicenter, randomized, double-blind, placebo-controlled, phase 2 trial of ceperognastat in participants with early symptomatic AD was conducted at 72 centers in Australia, Canada, Japan, Poland, and the US from September 2021 to July 2025. The study adhered to the ethical principles outlined in the Declaration of Helsinki²⁰ and other international guidelines. All participants provided written, informed consent before any study-related procedures. The study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.²¹ The protocol was approved by an ethics committee at each participating center, and unblinded safety data were reviewed approximately every 3 months by an independent unblinded external data and safety monitoring committee. Participants were compensated for study participation. The study protocol and statistical analysis plan are provided in Supplements 1 and 2, respectively.

Eligible participants were aged 60 to 85 years and had a Mini-Mental State Examination (MMSE) score of 22 to 30, Clinical Dementia Rating Scale (CDR) Global Score of 0.5 or 1 with a memory box score greater than or equal to 0.5, elevated plasma level of tau phosphorylated at residue 217 (p-tau217), and evidence of elevated brain tau levels by flortaucipir F18 positron emission tomography (PET) scan at the time of screening. Demographic information, including race and ethnicity, was collected to allow for characterization of potential differences in treatment effects by demographic characteristic. Race and ethnicity were self-reported by participants based on fixed categories. All study participants and study staff were blinded to treatment assignment during the treatment phase.