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NCT Number: NCT07636811

A Study to Evaluate Mivelsiran in Adult Participants With Early-Stage Down Syndrome-Associated Alzheimer's Disease (DS-AD)

The purpose of the study is to evaluate the effect of mivelsiran in adult participants with early-stage DS-AD and to characterize the safety, tolerability, and pharmacodynamics (PD) of mivelsiran. The study will be conducted over 2 periods: a 24-month double-blind period and an optional 12-month open-label treatment extension (OLE) period. The estimated duration of study participation, inclusive of screening, treatment, and additional safety follow-up, is up to 39 months.

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Key information

Conditions

Down Syndrome-Associated Alzheimer's Disease (DS-AD) Abnormalities, Multiple Chromosome Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Down Syndrome Genetic Diseases, Inborn Intellectual Disability Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations

Age range

40 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Clinical Study Site, Maitland, Florida, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Clinical diagnosis of Down-Syndrome (DS) associated with trisomy 21
  • Positive amyloid PET scan
  • Cognitively stable in the opinion of the investigator
  • Seizures must be well controlled with no occurrence of seizures in the 6 months prior to screening

Exclusion criteria

  • Has severe intellectual disability (ID)
  • Has a history of DS regression disorder
  • Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2×upper limit of normal (ULN) at Screening
  • Has estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m^2 at Screening
  • Has recently received an investigational agent
  • Has had treatment with amyloid-targeting antibody
  • Comorbidities such as obstructive sleep apnea and hypothyroidism that are not well controlled

Note: other protocol defined inclusion / exclusion criteria apply

Treatment and study plan

Mivelsiran

Drug

Mivelsiran will be administered intrathecally

Other names: ALN-APP

Placebo

Drug

Placebo will be administered intrathecally

Primary outcomes

  1. Double-Blind Period: Change from baseline in brain amyloid burden measured in centiloids (CLs)

    Time frame: Up to 24 months

Secondary outcomes

  1. Double-Blind Period: Change from baseline in APP protein concentration in cerebrospinal fluid (CSF)

    Time frame: Up to 24 months

  2. Double-Blind Period: Change from baseline in the concentration of amyloid beta proteins in CSF

    Time frame: Up to 24 months

  3. Double-Blind Period: Change from baseline in the concentration of tau proteins in plasma

    Time frame: Up to 24 months

  4. Double-Blind Period: Change from baseline on a cognitive scale

    Time frame: Up to 24 months

  5. Double-blind Period and Open-label Extension (OLE) Period: Frequency of adverse events (AEs)

    Time frame: Up to 36 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 Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study, to Evaluate Efficacy, Safety, Tolerability, and Pharmacodynamics of Intrathecally Administered Mivelsiran in Adult Participants With Early-Stage Down Syndrome-Associated Alzheimer's Disease (DS-AD)

Important dates

Study start
2026
Primary completion
2030
Study completion
2031
First posted
Jun 9, 2026
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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