Alzheimer's Disease
Conditions
Keywords
AD, Dementia
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
Interventions
DRUGALN-5288
ALN-5288 will be administered IT.
DRUGPlacebo
Placebo will be administered IT.
Sponsors
Alnylam Pharmaceuticals
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of Adverse Events (AEs) | Up to 32 months |
| Severity of AEs | Up to 32 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Canada, Netherlands, Spain, United Kingdom
Contacts
CONTACTClinical Trial Information Line
STUDY_DIRECTORMedical Director
Alnylam Pharmaceuticals
Outcome results
None listed