Alzheimer DiseasePhase 1NCT06673069
Hero: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) and Pharmacodynamics (PD) of ION269 in Participants With Down Syndrome (DS) at Risk for Alzheimer's Disease (AD)
A Phase 1 study testing ION269 in people with Alzheimer Disease and Down Syndrome, run by Ionis Pharmaceuticals, Inc. at 6 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 35 to 55 years
- Conditions the study is for
- Alzheimer Disease, Down Syndrome
- What is being tested?
- ION269
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 20 Dec 2024to 3 Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Has a reliable study partner, that is, a parent, sibling, or caregiver ≥ 21 years of age, who has known the participant for > 6 months (i.e., a reliable and competent individual with a close relationship with the participant) 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.
- Is assessed as being cognitively stable.
- Is in good health as evidenced by medical history, physical, and neurological examination, and with no diagnosis of dementia or mild cognitive impairment.
Who cannot join
- 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/tau-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).
- Note: Other protocol defined inclusion/exclusion criteria may apply.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
Ionis Investigative Site
Indianapolis, Indiana, 46202
Ionis Investigative Site
Kansas City, Kansas, 66205
Ionis Investigative Site
Lexington, Kentucky, 40536
Ionis Investigative Site
Madison, Wisconsin, 53705
Ionis Investigative Site
St Louis, Missouri, 63110
About this study
Official title: A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION269 in Adults With Down Syndrome (Hero Study)
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.
Read the detailed description
This is a phase 1b multi-center, open-label, single ascending dose (SAD) study in adult participants with Down syndrome with evidence of brain amyloid positivity. Participants will be examined in 3 separate cohorts and will receive a single dose of study drug during the 36-week treatment period, followed by a 4-week follow-up period.
- Conditions
- Alzheimer Disease, Down Syndrome
- Being tested
- ION269
- Medical subject headings
- Alzheimer Disease, Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ION269Drug
Administered as intrathecal (IT) injection.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Participants will receive a single dose of ION269. Receives: Drug: ION269 |
| Cohort 2 | Experimental | Participants will receive a single dose of ION269. Receives: Drug: ION269 |
| Cohort 3 | Experimental | Participants will receive a single dose of ION269. Receives: Drug: ION269 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: Up to approximately Week 40
Number of Participants With Change from Baseline in Laboratory Assessments
Measured: Up to approximately Week 40
Number of Participants With Change from Baseline in Cerebrospinal fluid (CSF) Safety Laboratory Assessments
Measured: Up to approximately Week 40
Number of Participants With Change From Baseline in Vital Signs
Measured: Up to approximately Week 40
Number of Participants With Change From Baseline in Weight
Measured: Up to approximately Week 40
Number of Participants With Change From Baseline in Electrocardiogram (ECG)
Measured: Up to approximately Week 40
Number of Participants With Change From Baseline in Suicide Risk Measured by Columbia Suicide Severity Rating Scale [C-SSRS] Child Version
Measured: Up to approximately Week 40
Number of Participants With Change From Baseline in Physical and Neurological Examination Findings
Measured: Up to approximately Week 40
Secondary outcomes (6)
CSF Concentrations of ION269
Measured: Pre-dose and post-dose at multiple timepoints up to Week 40
Area Under the Plasma Concentration-time Curve (AUC) of ION269 From Time 0 to Time of Last Measurable Concentration
Measured: Pre-dose and post-dose at multiple timepoints up to Week 40
Maximum Observed Plasma Concentration (Cmax) of ION269
Measured: Pre-dose and post-dose at multiple timepoints up to Week 40
Time to reach Cmax (Tmax) of ION269
Measured: Pre-dose and post-dose at multiple timepoints up to Week 40
Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Alpha (sAPPα)
Measured: Baseline (Day 1) and Week 36
Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Beta (sAPPβ)
Measured: Baseline (Day 1) and Week 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2024
- Study start20 Dec 2024
- Primary completion3 Dec 2025
- Study completion3 Dec 2025
Why it stopped: Sponsor decision to terminate study early. Decision not based on safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06673069
- Sponsor's protocol ID
- ION269-CS1
- Other IDs
- 2023-509257-31-00, U1111-1306-9498, 2023
- Status last verified
- Feb 2026
- First submitted
- 31 Oct 2024
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION269 in Adults With Down Syndrome (Hero Study)
- ClinicalTrials.gov ID
- NCT06673069
- Acronym / sponsor ID
- ION269-CS1
- Conditions
- Alzheimer Disease, Down Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision to terminate study early. Decision not based on safety concerns.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Dec 2024 (actual)
- Primary completion
- 3 Dec 2025 (actual)
- Study completion
- 3 Dec 2025 (actual)
- First posted
- 4 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a phase 1b multi-center, open-label, single ascending dose (SAD) study in adult participants with Down syndrome with evidence of brain amyloid positivity. Participants will be examined in 3 separate cohorts and will receive a single dose of study drug during the 36-week treatment period, followed by a 4-week follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: ION269Participants will receive a single dose of ION269. |
| Cohort 2 | Experimental | Drug: ION269Participants will receive a single dose of ION269. |
| Cohort 3 | Experimental | Drug: ION269Participants will receive a single dose of ION269. |
Who may qualify
- Ages
- 35 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Has a reliable study partner, that is, a parent, sibling, or caregiver ≥ 21 years of age, who has known the participant for > 6 months (i.e., a reliable and competent individual with a close relationship with the participant) 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.
- Is assessed as being cognitively stable.
- 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 (4 listed)
- 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/tau-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).
- Note: Other protocol defined inclusion/exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ION269Administered as intrathecal (IT) injection. | Drug | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to approximately Week 40
Number of Participants With Change from Baseline in Laboratory Assessments
Time frame: Up to approximately Week 40
Number of Participants With Change from Baseline in Cerebrospinal fluid (CSF) Safety Laboratory Assessments
Time frame: Up to approximately Week 40
Number of Participants With Change From Baseline in Vital Signs
Time frame: Up to approximately Week 40
Number of Participants With Change From Baseline in Weight
Time frame: Up to approximately Week 40
Number of Participants With Change From Baseline in Electrocardiogram (ECG)
Time frame: Up to approximately Week 40
Number of Participants With Change From Baseline in Suicide Risk Measured by Columbia Suicide Severity Rating Scale [C-SSRS] Child Version
Time frame: Up to approximately Week 40
Number of Participants With Change From Baseline in Physical and Neurological Examination Findings
Time frame: Up to approximately Week 40
6 secondary outcomes
CSF Concentrations of ION269
Time frame: Pre-dose and post-dose at multiple timepoints up to Week 40
Area Under the Plasma Concentration-time Curve (AUC) of ION269 From Time 0 to Time of Last Measurable Concentration
Time frame: Pre-dose and post-dose at multiple timepoints up to Week 40
Maximum Observed Plasma Concentration (Cmax) of ION269
Time frame: Pre-dose and post-dose at multiple timepoints up to Week 40
Time to reach Cmax (Tmax) of ION269
Time frame: Pre-dose and post-dose at multiple timepoints up to Week 40
Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Alpha (sAPPα)
Time frame: Baseline (Day 1) and Week 36
Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Beta (sAPPβ)
Time frame: Baseline (Day 1) and Week 36
Results and safety
The study was stopped early (reason given: Sponsor decision to terminate study early. Decision not based on safety concerns.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
- Individual participant dataSharing planned: Yes. Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ION269 in people with Alzheimer Disease and Down Syndrome, run by Ionis Pharmaceuticals, Inc. at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision to terminate study early. Decision not based on safety concerns.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Up to approximately Week 40). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2026.