A Study to Evaluate the Safety and Tolerability of ALN-APP in Patients With EOAD

A Randomized, Double-blind, Placebo-controlled Single Ascending Dose and Open-label Multi-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ALN-APP in Adult Patients With Early-onset Alzheimer's Disease (EOAD)

The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of a single dose and multiple doses of ALN-APP administered by intrathecal (IT) injection in adult patients with early-onset Alzheimer's Disease (EOAD). Maximum treatment duration for Part A: single dose. Maximum treatment duration for Part B: 12 months.

Inclusion Criteria:

• Has mild cognitive impairment or mild dementia due to EOAD
• Has Clinical Dementia Rating (CDR) global score 0.5 or 1.0 and Mini Mental State Examination (MMSE) >20

Exclusion Criteria:

• Has Non-Alzheimer's disease dementia
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2×upper limit of normal (ULN)
• Has estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m^2 at Screening
• Has recently received an investigational agent
• Has recent treatment with amyloid-targeting antibody

Note: other protocol defined inclusion / exclusion criteria apply