Statistics and reproducibility
DISEASE, INFUSION REACTION, SECONDARY
Statistical analyses were performed using SAS version 9.4. The analyses were performed by one statistical programmer, and the results were independently programmatically checked by a second statistical programmer and reviewed by two statisticians. The prespecified unblinded analysis was performed at the completion of the placebo-controlled period. Efficacy analyses were performed on the full analysis set (that is, all randomized participants who received the study treatment (gosuranemab or placebo)). Four participants were randomized but not dosed and excluded from the analysis. Secondary objective (CDR-SB) and key exploratory endpoints were analyzed using a mixed model for repeated measures (MMRM), with fixed effects of treatment, time, interaction between treatment and time, baseline value of the parameter of interest, interaction between the baseline value of the parameter of interest and time, baseline MMSE score, region, disease stage and baseline use of AD symptomatic medications. Model diagnostics were performed to evaluate the normality of data distribution and the impact of outliers. Missing data were assumed to be missing at random. Similar models were used for key secondary and exploratory endpoints. Additional analyses of efficacy endpoints from the LTE period were performed using data from the placebo-controlled and LTE periods.Biomarker analyses (CSF testing, tau PET and structural MRI) were performed on either the evaluable set or the modified evaluable set for each type of analysis, in which the evaluable set consisted of all participants in the full analysis set who underwent the relevant procedure (lumbar puncture, PET or MRI) and the modified evaluable set consisted of the subset of the evaluable set with at least one postbaseline measurement of the specific parameter being analyzed. Biomarker analyses used an MMRM similar to that used for efficacy analyses; however, age was also used as a covariate for tau PET and MRI analyses, and region was not used as a covariate for CSF and tau PET analyses.All safety analyses, except MRI safety analyses, were performed using data from all randomized participants who received at least one dose of the study treatment. MRI safety analyses were performed using data from all participants who received the study treatment and had at least one safety MRI scan after the baseline visit. Infusion reactions were defined as AEs that occurred on the day of or up to 2 days after an infusion.