Amyloid Lowering for Alzheimer's in Down's With Donanemab Investigation

Summary

The goal of this clinical trial is to learn if donanemab can reduce levels of amyloid in the brain, and if donanemab is safe and well-tolerated in participants with Down syndrome.

The main questions it aims to answer are: Does donanemab reduce amyloid in the brain? Is donanemab safe and well-tolerated in people with Down syndrome? Researchers will compare donanemab to a placebo (a look-alike substance that contains no drug) to see if donanemab works to reduce levels of amyloid in the brain.

Participants in the study will be 35-50 years old and will be in the study for 12 months. Participants will then stay in the study for an additional 12 months in an long-term extension where all participants will receive donanemab. Participants who had a reduction in amyloid (measured by amyloid brain scan) by the end of the first 12 months will receive placebo for the long-term extension, while participants who did not have an amyloid reduction will receive study donanemab for the long-term extension. Everyone (participants and study staff) will remain blinded to treatment for the duration of the study.

Participants will:

* Have intravenous (IV) infusions of donanemab (or placebo) every 4 weeks
* Visit the clinic once every other month for checkups and tests. These tests will include brain scans (magnetic resonance imaging \[MRI\] and positron emission tomography \[PET\] ), blood draws and memory tests.
* Have a study partner who who can provide information about the participant and can join participant for some of the study visits.

Conditions

• Down Syndrome (DS)
• Down Syndrome (Trisomy 21)
• Alzheimer Disease
• Amyloid Beta Protein

Interventions

DRUG

Placebo

The control product (placebo) will be supplied in vials containing 350 mg/20 mL of donanemab Placebo for donanemab is supplied to the clinical site to match the active study intervention and contains only inactive ingredients. Normal sterile saline solution (0.9% sodium chloride) will be used for dilution.

DRUG

Donanemab

Donanemab will be administered as an IV infusion every 4 weeks using an up-titration regimen that will allow participants to reach a target dose of 1400 mg within 24 weeks.

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• Eli Lilly and Company

  collaborator INDUSTRY

• Alzheimer's Clinical Trials Consortium

  collaborator OTHER

• Alzheimer's Therapeutic Research Institute

  collaborator OTHER

• Michael Rafii, MD, PhD

  lead OTHER

Principal Investigators

• Michael Rafii, MD, PhD · University of Southern California (USC) Keck School of Medicine, Alzheimer's Therapeutic Research Institute (ATRI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

35 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-01

Primary Completion

2028-12-31

Completion

2028-12-31

FDA Drug

Yes