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TerminatedPhase 1

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 1b Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION269 in Adults With Down Syndrome (Hero Study)

Asset

ION269

Listed sites

6

Recruiting sites

-

Enrollment

1

actual

Study population

Alzheimer’s disease

Key I/E criteria

Amyloid biomarker required (PET)Study partner/caregiver requiredMRI contraindications excluded

Primary endpoints

Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)Laboratory AssessmentsCerebrospinal fluid (CSF) Safety Laboratory Assessments

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Ctis2023-509257-31-00
Org study IDION269-CS1
NCT IDNCT06673069
Secondary IDU1111-1306-9498WHO Number

Timeline

Milestones

Study first posted2024-11-04actual
Study start2024-12-20actual
Primary completion2025-12-03actual
Study completion2025-12-03actual
Last update posted2026-02-20actual

Assets

Drug assets

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age35 Years
Maximum age55 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

1. 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.

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

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

4. Is assessed as being cognitively stable.

5. Is in good health as evidenced by medical history, physical, and neurological examination, and with no diagnosis of dementia or mild cognitive impairment

Exclusion criteria

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

2. 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.

3. 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.

Endpoints (14)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK
6
Other (unclassified)
4
Amyloid biomarkers
2
Fluid / digital biomarkers
2

Amyloid biomarkers

2 endpoints
Secondary/protocol endpoint

Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Alpha (sAPPα)

Time frame:Baseline (Day 1) and Week 36

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Beta (sAPPβ)

Time frame:Baseline (Day 1) and Week 36

change from baseline, improvement

Fluid / digital biomarkers

2 endpoints
Primary/protocol endpoint

Number of Participants With Change from Baseline in Cerebrospinal fluid (CSF) Safety Laboratory Assessments

Time frame:Up to approximately Week 40

change from baseline, improvement

Secondary/protocol endpoint

CSF Concentrations of ION269

Time frame:Pre-dose and post-dose at multiple timepoints up to Week 40

concentration, descriptive

Safety / tolerability / PK

6 endpoints
Primary/protocol endpoint

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time frame:Up to approximately Week 40

event count, event

Primary/protocol endpoint

Number of Participants With Change From Baseline in Vital Signs

Time frame:Up to approximately Week 40

change from baseline, event

Primary/protocol endpoint

Number of Participants With Change From Baseline in Electrocardiogram (ECG)

Time frame:Up to approximately Week 40

change from baseline, event

Secondary/protocol endpoint

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

concentration, descriptive

Secondary/protocol endpoint

Maximum Observed Plasma Concentration (Cmax) of ION269

Time frame:Pre-dose and post-dose at multiple timepoints up to Week 40

concentration, descriptive

Secondary/protocol endpoint

Time to reach Cmax (Tmax) of ION269

Time frame:Pre-dose and post-dose at multiple timepoints up to Week 40

time to event, event

Other (unclassified)

4 endpoints
Primary/protocol endpoint/low confidence

Number of Participants With Change from Baseline in Laboratory Assessments

Time frame:Up to approximately Week 40

change from baseline, improvement

Primary/protocol endpoint/low confidence

Number of Participants With Change From Baseline in Weight

Time frame:Up to approximately Week 40

change from baseline, improvement

Primary/protocol endpoint/low confidence

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

change from baseline, improvement

Primary/protocol endpoint/low confidence

Number of Participants With Change From Baseline in Physical and Neurological Examination Findings

Time frame:Up to approximately Week 40

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.