RecruitingPhase 1

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

Lead sponsor

Alnylam Pharmaceuticals

Asset

ALN-5288

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•Amyloid biomarker required (PET/CSF)

Primary endpoints

•Adverse Events (AEs)•Severity of AEs

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Ctis2025-522582-30-00

Org study IDALN-5288-001

NCT IDNCT07214727

Timeline

Milestones

Study first posted2025-10-09actual

Study start2025-10-15actual

Last update posted2026-06-12actual

Primary completion2030-03-06estimated

Study completion2030-03-06estimated

Assets

Drug assets

ALN-5288

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age40 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (9)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Tau biomarkers

Fluid / digital biomarkers

Safety / tolerability / PK

Tau biomarkers

2 endpoints

Secondary/protocol endpoint

Concentration of Total Tau (t-Tau) Protein in CSF Over Time

Time frame:Up to 32 months

concentration, descriptive

Secondary/protocol endpoint

Change from Baseline in Concentration of t-Tau Protein in CSF Over Time

Time frame:Up to 32 months

change from baseline, improvement

Fluid / digital biomarkers

2 endpoints

Secondary/protocol endpoint

Change from Baseline in Concentration of ALN-5288 CSF Ct

Time frame:Up to 32 months

change from baseline, improvement

Secondary/protocol endpoint

Concentration of ALN-5288 in CSF

Time frame:Up to 32 months

concentration, descriptive

Safety / tolerability / PK

1 endpoint

Primary/protocol endpoint

Frequency of Adverse Events (AEs)

Time frame:Up to 32 months

event count, event

Other (unclassified)

4 endpoints

Primary/protocol endpoint/low confidence

Severity of AEs

Time frame:Up to 32 months

descriptive

Secondary/protocol endpoint/low confidence

Concentration of ALN-5288 in Plasma Over Time (Ct)

Time frame:Up to 32 months

concentration, descriptive

Secondary/protocol endpoint/low confidence

Concentration of ALN-5288 in Plasma

Time frame:Up to 32 months

concentration, descriptive

Secondary/protocol endpoint/low confidence

Concentration of ALN-5288 in Urine

Time frame:Up to 32 months

concentration, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.