A Study to Evaluate the Safety and Tolerability of ALN-APP in Patients With EOAD

Phase 1RecruitingNCT05231785

Alnylam Pharmaceuticals60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Early-Onset Alzheimer Disease

Interventions

ALN-APPDRUG

ALN-APP will be administered intrathecally (IT)

PlaceboDRUG

Placebo will be administered IT

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

Clinical Trial Site

La Jolla, California, United States

COMPLETED

Clinical Trial Site

Indianapolis, Indiana, United States

RECRUITING

Clinical Trial Site

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Part A: Frequency of Adverse Events

Time frame: Up to 12 months

Part B: Frequency of Adverse Events

Time frame: Up to 24 months

Secondary Outcomes

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)

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: Up to 1 day

Part A and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF

Time frame: Part A up to 12 months; Part B up to 24 months

Central Contacts

Alnylam Clinical Trial Information Line

CONTACT

1-877-ALNYLAM clinicaltrials@alnylam.com

Alnylam Clinical Trial Information Line

CONTACT

1-877-256-9526 clinicaltrials@alnylam.com

Data from ClinicalTrials.gov

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