Alzheimer's DiseasePhase 1NCT07214727
A Study to Evaluate ALN-5288 in Patients With Alzheimer's Disease
A Phase 1 study testing ALN-5288 in people with Alzheimer's Disease, run by Alnylam Pharmaceuticals at 13 sites in 4 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- ALN-5288
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 13 sitesin 4 countries
- Study dates
- 15 Oct 2025to 6 Mar 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
13 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
13 sites in 4 countries
Canada4 sites, 4 recruiting
- Recruiting
Clinical Trial Site
Montreal, H3G 1H9
- Recruiting
Clinical Trial Site
Ottawa, K1Z 1G3
- Recruiting
Clinical Trial Site
Toronto, M3B 2S7
- Not yet recruiting
Clinical Trial Site
Toronto, M5T 2S8
United Kingdom4 sites, 4 recruiting
- Recruiting
Clinical Trial Site
Glasgow, G51 4TF
- Recruiting
Clinical Trial Site
London, WC1N 3BG
- Recruiting
Clinical Trial Site
Sheffield, S10 2JF
- Recruiting
Clinical Trial Site
Southampton, SO16 6YD
Spain3 sites, 3 recruiting
- Not yet recruiting
Clinical Trial Site
Barcelona, 08036
- Recruiting
Clinical Trial Site
Madrid, 28040
- Not yet recruiting
Clinical Trial Site
Sant Cugat del Vallès, 08190
Netherlands2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
's-Hertogenbosch, 5223
- Recruiting
Clinical Trial Site
Amsterdam, 1081 GN
About this study
Official title: 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
- Conditions
- Alzheimer's Disease
- Being tested
- ALN-5288, Placebo
- Keywords
- AD, Dementia
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-5288Drug
ALN-5288 will be administered IT.
PlaceboDrug
Placebo will be administered IT.
| Study group | Role | What they receive |
|---|---|---|
| ALN-5288 | Experimental | Participants will be administered ALN-5288 in the Double-blind (DB) Period and Open-Label Extension (OLE) Period. Receives: Drug: ALN-5288 |
| Placebo + ALN-5288 | Placebo comparator | Participants will be administered placebo in the DB Period and ALN-5288 in the OLE Period. Receives: Drug: ALN-5288; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Adverse Events (AEs)
Measured: Up to 32 months
Severity of AEs
Measured: Up to 32 months
Secondary outcomes (7)
Concentration of Total Tau (t-Tau) Protein in CSF Over Time
Measured: Up to 32 months
Change from Baseline in Concentration of t-Tau Protein in CSF Over Time
Measured: Up to 32 months
Concentration of ALN-5288 in Plasma Over Time (Ct)
Measured: Up to 32 months
Change from Baseline in Concentration of ALN-5288 CSF Ct
Measured: Up to 32 months
Concentration of ALN-5288 in Plasma
Measured: Up to 32 months
Concentration of ALN-5288 in Urine
Measured: Up to 32 months
Concentration of ALN-5288 in CSF
Measured: Up to 32 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2025
- Study start15 Oct 2025
- Primary completion6 Mar 2030 (estimated)
- Study completion6 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07214727
- Sponsor's protocol ID
- ALN-5288-001
- Other IDs
- 2025-522582-30-00, 2025
- Status last verified
- Oct 2026
- First submitted
- 6 Oct 2025
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No