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)

Alnylam Pharmaceuticals8 sites in 4 countries60 target enrollmentFebruary 4, 2022

ConditionsEarly-Onset Alzheimer Disease

InterventionsALN-APP Placebo

Overview

Phase: Phase 1
Intervention: ALN-APP
Conditions: Early-Onset Alzheimer Disease
Sponsor: Alnylam Pharmaceuticals
Enrollment: 60
Locations: 8
Primary Endpoint: Part B: Frequency of Adverse Events
Status: Recruiting
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 4, 2022

End Date

April 20, 2029

Last Updated

2 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Alnylam Pharmaceuticals

Responsible Party

Sponsor

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

Arms & Interventions

Part A: ALN-APP

Participants will be administered a single dose of ALN-APP.

Intervention: ALN-APP

Part A: Placebo

Participants will be administered a single dose of placebo.

Intervention: Placebo

Part B:

Participants will be administered multiple doses of ALN-APP.

Intervention: ALN-APP

Outcomes

Primary Outcomes

Part B: Frequency of Adverse Events

Time Frame: Up to 24 months

Part A: Frequency of Adverse Events

Time Frame: Up to 12 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)(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)