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
2 other identifiers
interventional
50
4 countries
13
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2025
Longer than P75 for phase_1
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 6, 2025
CompletedFirst Posted
Study publicly available on registry
October 9, 2025
CompletedStudy Start
First participant enrolled
October 15, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 6, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 6, 2030
June 12, 2026
June 1, 2026
4.4 years
October 6, 2025
June 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Frequency of Adverse Events (AEs)
Up to 32 months
Severity of AEs
Up to 32 months
Secondary Outcomes (7)
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
- +2 more secondary outcomes
Study Arms (2)
ALN-5288
EXPERIMENTALParticipants will be administered ALN-5288 in the Double-blind (DB) Period and Open-Label Extension (OLE) Period.
Placebo + ALN-5288
PLACEBO COMPARATORParticipants will be administered placebo in the DB Period and ALN-5288 in the OLE Period.
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Alnylam Pharmaceuticalslead
- Regeneron Pharmaceuticalscollaborator
Study Sites (13)
Clinical Trial Site
Montreal, H3G 1H9, Canada
Clinical Trial Site
Ottawa, K1Z 1G3, Canada
Clinical Trial Site
Toronto, M3B 2S7, Canada
Clinical Trial Site
Toronto, M5T 2S8, Canada
Clinical Trial Site
's-Hertogenbosch, 5223, Netherlands
Clinical Trial Site
Amsterdam, 1081 GN, Netherlands
Clinical Trial Site
Barcelona, 08036, Spain
Clinical Trial Site
Madrid, 28040, Spain
Clinical Trial Site
Sant Cugat del Vallès, 08190, Spain
Clinical Trial Site
Glasgow, G51 4TF, United Kingdom
Clinical Trial Site
London, WC1N 3BG, United Kingdom
Clinical Trial Site
Sheffield, S10 2JF, United Kingdom
Clinical Trial Site
Southampton, SO16 6YD, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Alnylam Pharmaceuticals
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 6, 2025
First Posted
October 9, 2025
Study Start
October 15, 2025
Primary Completion (Estimated)
March 6, 2030
Study Completion (Estimated)
March 6, 2030
Last Updated
June 12, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will not share