ALN-5288 injected into the spinal fluid for 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
This will test whether giving ALN-5288 into the spinal fluid is safe and how the medicine moves through and affects the body in people with mild cognitive impairment or dementia from Alzheimer's disease.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 50 (estimated) |
| Ages | 40 Years to 80 Years |
| Sex | All |
| Sponsor | Alnylam Pharmaceuticals Industry-sponsored |
| Locations | 11 sites (Montreal and 10 other locations) |
| Trial ID | NCT07214727 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1 interventional study that delivers ALN-5288 into the cerebrospinal fluid (intrathecal) and compares it with placebo to characterize safety and tolerability. The trial will measure pharmacokinetic and pharmacodynamic effects in blood and CSF after dosing. Eligible participants must have AD confirmed by CSF biomarkers or a positive amyloid PET within seven years and have mild cognitive impairment or dementia due to AD. Study visits are conducted at clinical sites in Montreal, Ottawa, and Toronto.
Who should consider this trial
Good fit: Ideal candidates are people with a clinical diagnosis of Alzheimer's disease (MCI or dementia due to AD) confirmed by CSF biomarkers or positive amyloid PET within seven years who can undergo intrathecal dosing and attend visits at the listed Canadian sites.
Not a fit: Patients with non‑AD dementia, significant liver or kidney dysfunction, uncontrolled blood pressure, active hepatitis or HIV infection, or clinically significant ECG abnormalities are unlikely to qualify or benefit from this early safety-focused trial.
Why it matters
Potential benefit: If safe and biologically active, ALN-5288 could offer a new way to target disease processes in the brain and potentially lead to future treatments for Alzheimer's disease.
How similar studies have performed: Intrathecal delivery of genetic or antisense therapies has shown success in other neurological diseases, but using this approach for Alzheimer's is relatively novel and clinical benefit in AD remains unproven.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Montreal and 10 other locations
- Clinical Trial Site — Montreal, Canada (Recruiting)
- Clinical Trial Site — Ottawa, Canada (Recruiting)
- Clinical Trial Site — Toronto, Canada (Recruiting)
- Clinical Trial Site — Toronto, Canada (Recruiting)
- Clinical Trial Site — 's-Hertogenbosch, Netherlands (Recruiting)
- Clinical Trial Site — Barcelona, Spain (Recruiting)
- Clinical Trial Site — Madrid, Spain (Recruiting)
- Clinical Trial Site — Glasgow, United Kingdom (Recruiting)
- Clinical Trial Site — London, United Kingdom (Recruiting)
- Clinical Trial Site — Sheffield, United Kingdom (Recruiting)
- Clinical Trial Site — Southampton, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Clinical Trial Information Line
- Email: clinicaltrials@alnylam.com
- Phone: 1-877-ALNYLAM
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.