A Phase 1 first-in-human trial of AADvac1 in 30 patients with mild to moderate AD showed excellent immunogenicity after 6 doses given over 24 weeks, with 29 of 30 patients demonstrating a robust IgG antibody response, with adverse effects including one seizure and one patient with existing microhemorrhages showing new microhemorrhages. [95] A subsequent 72 week follow-up trial (FUNDAMANT) showed sustained immune response after augmentation with 48- and 72-week boosters, and high antibody titers were associated with a decrease in hippocampal atrophy [96]. A larger Phase 2 trial enrolled 208 mild AD patients for 24 months of treatment (ADAMANT, NCT02579252), and a press release in September 2019 announced successful immunization without adverse events and a trend towards efficacy on functional outcomes, but results have not been published. A similar Phase 1 trial in 30 patients with non-fluent variant of primary progressive aphasia will assess safety and immunogenicity in this population (AIDA, NCT03174886), with results expected in late 2020.
