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

Not Applicable

Recruiting

• Conditions: Alzheimer's Disease
• Interventions: Drug: ALN-5288; Drug: Placebo

• Registration Number: NCT07214727
• Lead Sponsor: Alnylam Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-10-06
• Study First Submitted QC: 2025-10-06
• Study First Posted: 2025-10-09
• Study Start: 2025-10-15
• Status Verified: 2025-11
• Last Update Submitted: 2025-11-12
• Last Update Posted: 2025-11-13
• Primary Completion: 2030-03-31
• Study Completion: 2030-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ALN-5288	ALN-5288	Participants will be administered ALN-5288 in the Double-blind (DB) Period and Open-Label Extension (OLE) Period.
Placebo + ALN-5288	ALN-5288	Participants will be administered placebo in the DB Period and ALN-5288 in the OLE Period.
Placebo + ALN-5288	Placebo	Participants will be administered placebo in the DB Period and ALN-5288 in the OLE Period.

Primary Outcome Measures

Name	Time	Method
Frequency of Adverse Events (AEs)	Up to 32 months
Severity of AEs	Up to 32 months

Secondary Outcome Measures

Name	Time	Method
Concentration of Total Tau (t-Tau) Protein in CSF Over Time	Up to 32 months
Change from Baseline in Concentration of t-Tau Protein in CSF Over Time	Up to 32 months
Concentration of ALN-5288 in Plasma Over Time (Ct)	Up to 32 months
Change from Baseline in Concentration of ALN-5288 CSF Ct	Up to 32 months
Concentration of ALN-5288 in Plasma	Up to 32 months
Concentration of ALN-5288 in Urine	Up to 32 months
Concentration of ALN-5288 in CSF	Up to 32 months

Trial Locations

Locations (1)

Clinical Trial Site; 🇬🇧 Southampton, United Kingdom