Clinical trial NCT05231785: A Study to Evaluate the Safety and Tolerability of ALN-APP in Patients With EOAD
Official title: A Randomized, Double-blind, Placebo-controlled Single Ascending Dose and Open-label Multi-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ALN-APP in Adult Patients With Early-onset Alzheimer's Disease (EOAD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Early-Onset Alzheimer Disease
Keywords: EOAD
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-02-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Frequency of Adverse Events
timeFrame: Up to 12 months
measure: Part B: Frequency of Adverse Events
timeFrame: Up to 24 months
Secondary outcomes:
measure: 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)
timeFrame: Part A up to 12 months; Part B up to 24 months
measure: Part A and Part B: Area Under the Plasma Concentration-time Curve (AUC) of ALN-APP and of Potential Metabolites
timeFrame: Part A up to 12 months; Part B up to 24 months
measure: Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of ALN-APP and of Potential Metabolites
timeFrame: Part A up to 12 months; Part B up to 24 months
measure: Part A: Fraction of ALN-APP and Potential Metabolites Excreted in the Urine (fe)
timeFrame: Up to 1 day
measure: Part A and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF
timeFrame: Part A up to 12 months; Part B up to 24 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: Indianapolis
country: United States
facility: Clinical Trial Site
state: Indiana
city: Toronto
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Montréal
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Amsterdam
country: Netherlands
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: Sheffield
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: