A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION269 in Adults with Down Syndrome and Adults with Early Symptomatic Alzheimer's Disease (HERO Study)

Study on Safety and Tolerability of an Investigational Medication in Adults with Down Syndrome

J
Jill Fostad

Primary Investigator

Enrolling By Invitation
35 years - 55 years
All
Phase 1/2
1 participants needed
2 Locations

Brief description of study

The purpose of this study is to evaluate the safety and tolerability of ION269 in cognitively stable participants with DS who have evidence of brain amyloid positivity via amyloid-PET scan

THIS STUDY IS ENROLLING BY INVITATION ONLY

Detailed description of study

This is a multi-center, open-label, single-dose study in adult participants with DS. One dose level of intrathecal bolus (ITB)-administered Study Drug will be examined. A total of 20 participants are planned to be enrolled in two cohorts to receive ION269 30 or 60mg. Participants who discontinue during the Treatment Period may be replaced.

The first participant will be dosed as a sentinel. No other participant will be dosed until the investigator from the site at which the first participant was dosed has reviewed safety data through 28 days after dosing (e.g., TEAEs/SAEs, vital signs, ECGs, and clinical laboratory parameters) with the Sponsor or designee. Dosing of subsequent participants can commence after confirmation from the Sponsor for continuation.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Down Syndrome
  • Age: 35 years - 55 years
  • Gender: All

Key Inclusion Criteria:
Note that the capacity of the participant to provide consent will be evaluated by the Investigator
using their clinical judgment aided by the use of the MacArthur Competence Assessment Tool
for Clinical Research (MacCAT-CR).
The main inclusion criteria for participants in this study are the following:
• Is ≥ 35 and ≤ 55 years of age inclusive at the time of informed consent/assent.
• Has a diagnosis of DS.
• Has an intelligence quotient ≥ 45 (based on Kaufman Brief Intelligence Test-Second
Edition [KBIT-2]).
• Has evidence of amyloid pathology on amyloid-PET scan, defined as levels
≥ 20 centiloids.
− A previous amyloid-PET scan prior to Screening with documented result of
amyloid PET levels ≥ 20 centiloids can be used as evidence for amyloid positivity
for inclusion. A new Baseline amyloid-PET scan will still be required for the
purposes of the study assessments.
• Is cognitively stable as assessed by an independent clinician review using Screening
NTG-EDSD and mCRT results, and any historical NTG-EDSD and/or mCRT results
that may be available.
• Is in good health as evidenced by medical history, physical, and neurological
examination, and with no diagnosis of dementia or mild cognitive impairment.


Key Exclusion Criteria:
The main exclusion criterion for participants in this study is the following:
• 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 (e.g., moderate or severe untreated obstructive sleep
apnea, medical history of clinically significant B12 or folate deficiency that is
currently uncontrolled, clinically significant abnormalities of thyroid function, stroke,
or other cerebrovascular conditions), as per Investigator’s judgment.
• Is unable to complete MRI and amyloid PET procedures or has any
contraindications to having a brain MRI (e.g., MRI-incompatible pacemaker,
aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia
that cannot be medically managed without requiring general anesthesia).

Updated on 03 Jul 2025. Study ID: PSYC-IONIS-ION259-CS1-HERO, 23576

This study investigates the safety and tolerability of an investigational medication in adults with Down Syndrome (DS) who show signs of amyloid build-up in their brains. Down Syndrome is a genetic disorder caused by the presence of an extra chromosome, which can lead to developmental and cognitive challenges. Amyloid build-up is often associated with brain diseases, and this study aims to observe its effects in DS patients.

Participants in this study will receive a single dose of the investigational medication through an injection into the spinal fluid, known as an intrathecal bolus. The study will monitor safety data such as adverse events, vital signs, heart tests, and lab results for 28 days after dosing. This helps ensure the safety of participants before proceeding with more doses.

  • Who can participate: Adults aged 35 to 55 years with Down Syndrome and an IQ of 45 or higher can join. They must have amyloid build-up in their brain and be healthy without dementia or mild cognitive impairment.
  • Study details: Participants will be monitored for safety through various tests and assessments for 28 days after receiving the investigational medication.
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only