ION269 for Down Syndrome at Risk of Alzheimer's Disease

Not currently recruiting at 6 trial locations

Overseen By Ionis Pharmaceuticals

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Ionis Pharmaceuticals, Inc.

Disqualifiers: Unstable psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of ION269, a new treatment for adults with Down syndrome who show signs of brain amyloid positivity, a condition linked to Alzheimer's disease. Participants will receive a single dose to assess how their bodies handle it. The trial seeks adults with Down syndrome who have stable cognitive abilities and no signs of dementia, along with a supportive study partner to assist them throughout the process. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ION269 is likely to be safe for humans?

Research shows that ION269 remains in the early stages of testing, so there is limited information about its safety for people. As this study is in the first phase, the main goal is to assess how well people tolerate the drug. Early-phase studies typically focus on identifying side effects and understanding how the body processes the treatment. At this stage, it is too soon to determine long-term safety. If ION269 receives approval for other uses in the future, more information about its safety may become available. Currently, information on side effects and tolerance remains limited. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Alzheimer's disease in individuals with Down syndrome focus on managing symptoms or slowing disease progression. These standard options often include medications like cholinesterase inhibitors and memantine. However, ION269 is unique because it represents a new approach, potentially targeting the underlying disease mechanisms rather than just alleviating symptoms. This investigational treatment is designed to interact with specific genetic factors associated with Alzheimer's risk in Down syndrome, offering a more tailored and precise intervention. Researchers are excited about ION269 because it could pave the way for more effective and personalized therapies, offering hope for better outcomes in this vulnerable population.

What evidence suggests that ION269 might be an effective treatment for Down syndrome at risk of Alzheimer's disease?

Research has shown that people with Down syndrome are more likely to develop Alzheimer's disease due to their genetic makeup. This trial studies ION269 to determine if it can help reduce this risk. Although specific results for ION269 are not yet available, it is designed to target amyloid buildup in the brain, a key feature of Alzheimer's. The treatment aims to reduce or control the accumulation of amyloid proteins, which are believed to contribute to Alzheimer's disease. Early results from similar treatments suggest that targeting amyloid can slow the disease, offering hope that ION269 might have a similar effect. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with Down syndrome who are at risk for Alzheimer's. They need a reliable caregiver, an IQ of 45 or higher, evidence of brain amyloid on PET scans, and stable cognition without dementia or mild cognitive impairment.

Inclusion Criteria

Has a reliable study partner, that is, a parent, sibling, or caregiver ≥ 21 years of age, who has known the participant for > 6 months and is capable of providing accurate information about the participant's history, can attend all scheduled study visits and provide feedback regarding the participant's symptoms and performance as described in the protocol, and can comply with all study requirements and activities

Has a diagnosis of Down syndrome and has an intelligence quotient (IQ) ≥ 45

Has evidence of amyloid pathology on amyloid-positron emission tomography (PET) scan

Exclusion Criteria

Has unstable psychiatric illness, including psychosis, or untreated major depression within 90 days before Screening, as determined by the Investigator

Has any unstable medical condition likely to hamper the evaluation of safety and/or efficacy of the Study Drug, as per Investigator's judgment

Is unable to complete MRI and amyloid/tau-PET procedures or has any contraindications to having a brain MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of ION269 during the 36-week treatment period

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ION269

Trial Overview ION269 is being tested to see if it's safe and tolerable for those with Down syndrome showing signs that may lead to Alzheimer's. The study looks into how the body processes the drug and its effects on the body.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 1 Intervention

Participants will receive a single dose of ION269.

Group II: Cohort 2 Experimental Treatment 1 Intervention

Participants will receive a single dose of ION269.

Group III: Cohort 1 Experimental Treatment 1 Intervention

Participants will receive a single dose of ION269.

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Published Research Related to This Trial

A study involving 156 adults with Down syndrome (average age 39) found a significant relationship between amyloid beta (Aβ) and tau pathology in the brain, indicating that both are present and correlated in this population at risk for Alzheimer's disease.

Using PET scans, the research showed that higher levels of Aβ accumulation were associated with increased tau deposition, particularly starting from the Braak 3 region, which suggests a progression of Alzheimer's pathology in individuals with Down syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline. Tudorascu, DL., Laymon, CM., Zammit, M., et al.[2022]

Individuals with Down syndrome (DS) are at a high risk for developing Alzheimer's disease (AD), and recent studies have revealed both similarities and differences between Alzheimer's in DS and the more common late-onset Alzheimer's in the general population.

There is ongoing research into various therapeutic approaches for AD in DS, focusing on targets like β-amyloid and tau, with the aim of conducting clinical trials to treat or prevent AD in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzheimer's Disease in Down Syndrome: Progress in the Design and Conduct of Drug Prevention Trials. Rafii, MS.[2023]

Adults with Down syndrome have a significantly higher risk of developing Alzheimer's disease, with most showing signs of dementia by their late 60s, primarily due to the overexpression of the amyloid precursor protein gene on chromosome 21.

A multicenter longitudinal study funded by NIA/NICHD is currently investigating biomarkers of Alzheimer's disease in adults with Down syndrome, aiming to enhance our understanding of the disease in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Search for Biomarkers of Alzheimer's Disease in Down Syndrome. Handen, BL.[2023]

A study of 341 individuals, including adults with Down syndrome and carriers of autosomal dominant Alzheimer's disease mutations, revealed that those with Down syndrome exhibit similar cerebrospinal fluid (CSF) biomarker patterns to Alzheimer's disease carriers, indicating a shared disease mechanism.

Individuals with Down syndrome showed higher concentrations of amyloid beta and neuroinflammation markers, suggesting that they may experience unique pathological changes in Alzheimer's disease, particularly in the asymptomatic stage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of CSF biomarkers in Down syndrome and autosomal dominant Alzheimer's disease: a cross-sectional study. Fagan, AM., Henson, RL., Li, Y., et al.[2022]

A new composite cognitive test was developed from data of 312 participants with Down syndrome, which is sensitive to early cognitive decline and could be used in trials aimed at preventing Alzheimer's disease symptoms.

The composite includes tests for memory, language/executive functioning, selective attention, orientation, and praxis, making it a comprehensive tool for assessing cognitive changes in individuals with Down syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease. Aschenbrenner, AJ., Baksh, RA., Benejam, B., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06673069

NCT06673069 | Hero: A Study to Evaluate the Safety, ... The primary purpose of this study is to evaluate the safety and tolerability of ION269 in adults with Down syndrome with evidence of brain amyloid positivity.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12173829/

Current advances and unmet needs in Alzheimer's disease ... Longitudinal studies estimate a lifetime dementia risk exceeding 90%, with prevalence reaching 88%–100% after age 65—a marked contrast to 10%–15 ...

3. lumindidsc.org lumindidsc.org/wp-content/uploads/2025/07/June-Update.pdf

Understanding key differences among the current and ... People with Down syndrome face a heightened risk of developing Alzheimer's disease (AD) due to their unique genetic makeup. That makes them more vulnerable ...

4. withpower.com withpower.com/trial/phase-1-alzheimer-disease-10-2024-b4715

ION269 for Down Syndrome at Risk of Alzheimer's Disease This trial is for adults with Down syndrome who are at risk for Alzheimer's. They need a reliable caregiver, an IQ of 45 or higher, evidence of brain amyloid on ...

5. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06673069/

Trial | NCT06673069 The primary purpose of this study is to evaluate the safety and tolerability of ION269 in adults with Down syndrome with evidence of brain amyloid positivity.

6. ctv.veeva.com ctv.veeva.com/study/hero-a-study-to-evaluate-the-safety-tolerability-and-pharmacokinetics-pk-and-pharmacodynamics

Hero: A Study to Evaluate the Safety, Tolerability, and ... The primary purpose of this study is to evaluate the safety and tolerability of ION269 in adults with Down syndrome with evidence of brain amyloid positivity.

7. neurology.ionis.com neurology.ionis.com/sites/default/files/2025-03/Ionis%20Neurolgy%20Pipeline%20Booklet_US-GEN-2500001.pdf

IONIS' COMMITMENT TO NEUROLOGY1-3,a,b ION269 in Participants With Down Syndrome (DS) at. Risk for Alzheimer's Disease (AD) ... ION269 has not been evaluated for safety and efficacy by any regulatory.