Not yet recruitingPhase 2

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

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)

Lead sponsor

Alnylam Pharmaceuticals

Asset

Mivelsiran

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease

Key I/E criterion

•Amyloid biomarker required (PET)

Primary endpoint

•Amyloid PET Centiloid

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Ctis2025-523390-42-00

Org study IDALN-APP-003

NCT IDNCT07636811

Timeline

Milestones

Study first posted2026-06-09actual

Last update posted2026-07-15actual

Study start2026-07-31estimated

Primary completion2030-05-18estimated

Study completion2031-07-23estimated

Assets

Drug assets

Mivelsiran

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age40 Years

Maximum age55 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (6)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Amyloid biomarkers

Other (unclassified)

Fluid / digital biomarkers

Safety / tolerability / PK

Amyloid biomarkers

2 endpoints

Primary/protocol endpoint

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

Time frame:Up to 24 months

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Up to 24 months

change from baseline, improvement

Fluid / digital biomarkers

1 endpoint

Secondary/protocol endpoint

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

Time frame:Up to 24 months

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

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

Time frame:Up to 36 months

event count, event

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

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

Time frame:Up to 24 months

change from baseline, improvement

Secondary/protocol endpoint/low confidence

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

Time frame:Up to 24 months

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.