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NCT07636811PHASE2Recruiting

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

Alnylam Pharmaceuticals

Start Date

8/17/2026

Completion Date

7/30/2031

Summary

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.

Eligibility Criteria

Age Range: 40 years to 55 years

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

Interventions

DRUG

Mivelsiran

DRUG

Placebo

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Conditions

Down Syndrome-Associated Alzheimer's Disease (DS-AD)

Locations

Clinical Trial Site

Maitland, Florida 32751

United States

Clinical Trial Site

Naples, Florida 34105

United States

Clinical Trial Site

Indianapolis, Indiana 46037

United States

Clinical Trial Site

St Louis, Missouri 63110

United States

Clinical Trial Site

Barcelona,

Spain

Clinical Trial Site

Dos Hermanas,

Spain

Clinical Trial Site

Madrid,

Spain

Clinical Trial Site

Pamplona,

Spain

Clinical Trial Site

Seville,

Spain

Clinical Trial Site

Valencia,

Spain