ACI‐24 in adults with Down syndrome: Results of a phase 1b, randomized, placebo‐controlled study

Abstract Background The APP gene is located on chromosome 21 and thought to lead overproduction of beta‐amyloid (Aβ) in persons with trisomy (Down syndrome, DS). As a result, individuals DS are at high risk for developing Alzheimer’s disease (AD). ACI‐24 liposomal, T‐cell independent, anti‐Aβ vaccine which was assessed world’s first clinical phase 1b study adults DS. Method primary objectives this randomized, double‐blind, placebo‐controlled, dose‐escalation, Ib multi‐center were assess the safety tolerability aged 25‐45 years its effect induction serum antibody titers. secondary explore cognition, behavior, AD biomarkers, activation, brain volumes by MRI. Participants received subcutaneous injections (300 µg or 1000 µg) placebo (3:1 ratio) different timepoints up week 48 before entering 48‐week follow‐up period. Result Sixteen participants (9F/7M; mean age 32.9 [25‐41]) randomized into 2 dose‐level cohorts (n=8 each; 6 placebo). Treatment compliance 100%. very good no serious adverse events reported withdrawals due events. Most mild intensity unrelated unlikely related ACI‐24. No amyloid‐related imaging abnormalities (ARIA) changes markers CNS inflammation observed. Increases titers observed selected both treatment arms receiving as compared placebo. In addition, an increase plasma Aβ1‐40 Aβ1‐42 levels active groups. expected, consistent between groups other biomarkers measures small study. Conclusion safe well‐tolerated Evidence immunogenicity independent along pharmacodynamic target engagement effects measured Aβ 1‐40 1‐42 treated These results support pursuance accelerated development optimized formulation