ION269 for Down Syndrome at Risk of Alzheimer's Disease

Recruiting at 5 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

30 Participants Needed

Trial Summary

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.

What makes the drug ION269 unique for treating Alzheimer's disease in Down syndrome?

ION269 is unique because it specifically targets the genetic factors associated with Alzheimer's disease in individuals with Down syndrome, such as the overexpression of the amyloid precursor protein gene on chromosome 21, which is not addressed by standard Alzheimer's treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Comparison of CSF biomarkers in Down syndrome and autosomal dominant Alzheimer's disease: a cross-sectional study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease. [2022]