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

Alnylam Pharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Alzheimer's Disease

Treatments: Drug: ALN-5288; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07214727

ALN-5288-001

2025-522582-30-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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

Enrollment: 50 estimated patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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50 participants in 2 patient groups, including a placebo group

ALN-5288

Experimental group

Description:

Participants will be administered ALN-5288 in the Double-blind (DB) Period and Open-Label Extension (OLE) Period.

Treatment:

Drug: ALN-5288

Placebo + ALN-5288

Placebo Comparator group

Description:

Participants will be administered placebo in the DB Period and ALN-5288 in the OLE Period.

Treatment:

Drug: Placebo

Drug: ALN-5288