Study of the Efficacy and Safety of Various Anti-inflammatory Agents in Participants With Mild Cognitive Impairment or Mild Alzheimer's Disease

The purpose of this platform study is to evaluate the effect of anti-inflammatory agents on cognition in early Alzheimer's disease. Additionally, the safety and tolerability of these anti-inflammatory agents and the effects on central and peripheral inflammation will be evaluated.

This is a randomized, placebo-controlled, participant- and investigator-blinded study in participants with either mild cognitive impairment or mild Alzheimer's disease with evidence of peripheral inflammation. This study is using a platform design to be able to investigate different agents (therapies) in a perpetual manner. Each unique investigational agent will have a unique cohort of participants assigned. New cohorts of participants may be enrolled to investigate additional agents at unspecified timepoints throughout the study.

There are three periods in the study: screening period of 60 days that includes a baseline period of 7 days, a treatment period (20 weeks) and a follow-up period (28 days) and an additional follow-up visit for therapies with a longer washout.

Eligibility Criteria:
Inclusion Criteria:

* Male or female, age ≥ 45 years and ≤ 90 years at the time of signing the informed consent;
* Participant has a reliable study partner or caregiver can accompany the participant to all visits;
* A diagnosis of probable MCI due to AD or mild AD according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria;
* Confirmed amyloid and tau positivity via CSF sampling performed at screening;
* Mini-Mental State Examination (MMSE) total score of 20 to 24 (inclusive) at screening; OR, MMSE total score of 25-30 (inclusive) plus a DSST score at least 0.5 standard deviation (SD) below normative data at screening.

Exclusion Criteria:

* Use of an investigational agent or an approved product with the intent to modulate inflammation or modulate the course of AD (e.g., Tau ASOs, gene therapy, amyloid or tau vaccine):

  * Previous use of small molecules is allowed if discontinued for at least five half-lives, or at least 30 days from when the expected pharmacodynamic effect has returned to baseline prior to screening, whichever is longer
  * Previous use of monoclonal or polyclonal antibodies or other biologics is allowed if discontinued for at least five half-lives prior to screening
* Current medical or neurological condition that might impact cognition or performance on cognitive assessments, e.g., MCI not due to AD, non-Alzheimer dementia, Huntington's disease, Parkinson's disease, stroke, schizophrenia, bipolar disorder, active major depression, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), active seizure disorder, or history of traumatic brain injury associated with loss of consciousness and ongoing residual transient or permanent neurological signs/symptoms including cognitive deficits, and/or associated with skull fracture;
* If a historical MRI or CT scan has been performed, signs of major cerebrovascular disease shown on such scans (i.e., presence of infarction in greater than 25% of white matter; more than one lacune within basal ganglia or more than 2 lacunes in white matter);
* Diagnosis of vascular dementia prior to screening (e.g.., modified Hachinski Ischaemic Scale score \> 6 or those who meet the NINDS AIREN criteria for vascular dementia);