A Study to Evaluate the Safety and Tolerability of ALN-APP in Patients With EOAD
- Registration Number
- NCT05231785
- Lead Sponsor
- Alnylam Pharmaceuticals
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of a single dose and multiple doses of ALN-APP administered by intrathecal (IT) injection in adult patients with early-onset Alzheimer's Disease (EOAD). Maximum treatment duration for Part A: single dose. Maximum treatment duration for Part B: 12 months.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Inclusion Criteria
- Has mild cognitive impairment or mild dementia due to EOAD
- Has Clinical Dementia Rating (CDR) global score 0.5 or 1.0 and Mini Mental State Examination (MMSE) >20
Exclusion Criteria
- Has Non-Alzheimer's disease dementia
- Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2×upper limit of normal (ULN)
- Has estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m^2 at Screening
- Has recently received an investigational agent
- Has recent treatment with amyloid-targeting antibody
Note: other protocol defined inclusion / exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: ALN-APP Participants will be administered multiple doses of ALN-APP. Part A: Placebo Placebo Participants will be administered a single dose of placebo. Part A: ALN-APP ALN-APP Participants will be administered a single dose of ALN-APP.
- Primary Outcome Measures
Name Time Method Part B: Frequency of Adverse Events Up to 24 months Part A: Frequency of Adverse Events Up to 12 months
- Secondary Outcome Measures
Name Time Method Part A and Part B: Change from Baseline in Levels of Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein Alpha (sAPPα) and Soluble Amyloid Precursor Protein Beta (sAPPβ) Part A up to 12 months; Part B up to 24 months Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of ALN-APP and of Potential Metabolites Part A up to 12 months; Part B up to 24 months Part A: Fraction of ALN-APP and Potential Metabolites Excreted in the Urine (fe) Up to 1 day Part A and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF Part A up to 12 months; Part B up to 24 months Part A and Part B: Area Under the Plasma Concentration-time Curve (AUC) of ALN-APP and of Potential Metabolites Part A up to 12 months; Part B up to 24 months
Trial Locations
- Locations (1)
Clinical Trial Site
🇬🇧Sheffield, United Kingdom