NCT06911944

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

A Randomized, Double-Blind, Placebo-Controlled, Phase 4 Dose-Escalation Study Evaluating the Safety, Tolerability, and Efficacy of Donanemab in Adults With Down Syndrome

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Michael Rafii, MD, PhD · Academic / Other
• Sex: All
• Age: 35 Years – 50 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The conduct of this Phase 4 clinical study is intended to evaluate the effect of donanemab, a humanized monoclonal antibody, on brain amyloid (centiloids), in the non-demented DS population, with the primary objective of reducing amyloid accumulation. Concurrently, the study aims to investigate the safety and tolerability, and therapeutic potential of donanemab while maintaining the safety and tolerability observed in clinical studies in early AD populations up to the dose of 1400mg. Safety, tolerability, and efficacy of donanemab will be assessed in a non-demented DS population in the range of 35-50 years of age who are cognitively stable or have Mild Cognitive Impairment (MCI), which could indicate preclinical and prodromal AD, in a genetic population with ≥18 centiloids on amyloid-PET. The study will have a duration of approximately 12 months (52 weeks). A long-term extension (LTE) will also be included, lasting an additional 12 months (52 weeks).

Conditions

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

Interventions

Type	Name	Description
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.
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.

Timeline

• Start date: 2026-08-01
• Primary completion: 2028-12-31
• Completion: 2028-12-31
• First posted: 2025-04-04
• Last updated: 2025-11-24

Regulatory

• FDA-regulated drug study