This is a Phase 1b, multicenter, randomized, placebo-controlled, double-blind, multiple ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL628 in participants with early Alzheimer's disease (AD), defined as mild cognitive impairment, or mild AD with biomarker evidence of amyloid positivity.
Note: In the Netherlands, this study includes an open-label extension.
BMI of ≥18 to < 32 kg/m2 and body weight of ≥45 kg
Have a diagnosis of probable AD dementia based on NIA AA 2011 criteria, including amnestic or nonamnestic presentation at screening
Have supportive evidence of AD pathology via historical records or laboratory testing at screening for amyloid positivity
A Clinical Dementia Rating global score of 0.5 or 1
Have clinically significant neurological or cognitive disorders affecting the CNS other than AD, as determined by the investigator
Have clinically significant psychiatric conditions
Have any history of unstable or poorly controlled endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, hematological, or other significant medical condition that, in the opinion of the investigator, may interfere with the completion or interpretation of study assessment
Have had a malignancy within 5 years before screening, except fully resected basal cell carcinoma or other malignancies (such as prostate cancer) at low risk of recurrence, depending on investigator and medical monitor agreement