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NCT Number: NCT05231785

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

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.

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Key information

Conditions

Early-Onset Alzheimer Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Trial Site, Montreal, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ALN-APP

Drug

ALN-APP will be administered intrathecally (IT)

Other names: mivelsiran

Placebo

Drug

Placebo will be administered IT

Primary outcomes

  1. Part A: Frequency of Adverse Events

    Time frame: Up to 12 months

  2. Part B: Frequency of Adverse Events

    Time frame: Up to 42 months

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. Part A: Fraction of ALN-APP and Potential Metabolites Excreted in the Urine (fe)

    Time frame: Up to 1 day

  5. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Alnylam Clinical Trial Information Line

CONTACT

[email protected]

1-877-ALNYLAM

Alnylam Clinical Trial Information Line

CONTACT

[email protected]

1-877-256-9526

Sponsors and collaborators

Lead sponsor

Alnylam Pharmaceuticals

Industry

Registry information

Official study 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)

Important dates

Study start
2022
Primary completion
2029
Study completion
2029
First posted
Feb 9, 2022
Registry last updated
Jul 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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