A Study to Evaluate ALN-5288 in Patients With Alzheimer's Disease

A Phase 1, Randomized, Placebo-controlled Study With a Double Blind Period With Open-label Extension Period to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ALN-5288 in Adult Patients With Alzheimer's Disease

The purpose of this study is to:

• Evaluate the safety and tolerability of intrathecal (IT) ALN-5288 in patients with Alzheimer's Disease (AD)
• Evaluate the pharmacodynamic (PD) and pharmacokinetic (PK) effects of ALN-5288 after dose administration

Inclusion Criteria:

• Is able and willing to meet all study requirements in the opinion of the Investigator
• Has a diagnosis of Alzheimer's disease (AD) based on clinical findings supported by cerebrospinal fluid (CSF) biomarkers or positive positron emission tomography (PET) amyloid imaging within 7 years prior to screening
• Has mild cognitive impairment (MCI) or dementia due to AD

Exclusion Criteria:

• Has non-AD dementia
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× upper limit of normal (ULN)
• Has total bilirubin >1.5×ULN
• Has known human immunodeficiency virus infection
• Has history of hepatitis C virus or current hepatitis B virus infection
• Has systolic blood pressure >160 mmHg and/or a diastolic blood pressure >100 mmHg after 10 minutes of rest at screening
• Has an estimated glomerular filtration (eGFR) of <45 mL/min/1.73 m^2 at screening
• Has clinically significant ECG abnormalities at screening
• Has uncontrolled psychiatric disease, including patients deemed by the Investigator to be at significant risk of suicide, major depressive episode, psychosis, confusional state, or violent behavior
• Has history of bleeding diathesis or coagulopathy due to chronic conditions
• Has a medical history of brain or spinal disease that would interfere with the IT injection and LP procedures
• Has history of uncontrolled seizures within the last 6 months prior to Screening