Alzheimer's Tau Platform: Regimen A - AADvac1

The Alzheimer's Tau Platform (ATP) is a multi-center platform trial to evaluate the safety and effectiveness of tau-directed therapies, alone or in combination with donanemab, in adults aged 50-80 with late preclinical or early prodromal Alzheimer's disease. This platform trial allows for the simultaneous testing of multiple tau therapies under a shared master protocol. This means that multiple investigational products will be tested simultaneously or sequentially. Each investigational product will be tested in a regimen. The ATP Master Protocol is registered as NCT06957418.

Once a participant enrolls into the Master Protocol and meets all eligibility criteria, the participant will be eligible to be randomized into a currently enrolling regimen. All participants will have an equal chance of being randomized to any currently enrolling regimen.

Participants randomized to Regimen A - AADvac1 will be randomized in a 1:1:1 ratio to either AADvac1 alone, combination AADvac1 therapy with donanemab, or donanemab alone (active control). The allocation ratio may be change based on the number of concurrent active regimens to ensure appropriate number of individuals randomized to the control arm across all active regimes.

Regimen A will enroll by invitation, as participants may not choose to enroll in a given regimen. Participants must first enroll into the Master Protocol and be eligible to participate in the Master Protocol before being able to be randomly assigned to Regimen A.

For a list of enrolling sites, please see the ATP Master Protocol under NCT06957418.

Inclusion criteria

• No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT06957418).

Exclusion criteria

• No additional exclusion criteria beyond the exclusion criteria specified in the Master Protocol (NCT06957418).