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)

Stopped: Sponsor decision to terminate study early. Decision not based on safety concerns.

United States1 participantsStarted 2024-12-20

Plain-language 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.

Who can participate

Age range35 Years – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 (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.

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 (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).

What they're measuring

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

Timeframe: Up to approximately Week 40

Number of Participants With Change from Baseline in Laboratory Assessments

Timeframe: Up to approximately Week 40

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

Timeframe: Up to approximately Week 40

Number of Participants With Change From Baseline in Vital Signs

Timeframe: Up to approximately Week 40

Number of Participants With Change From Baseline in Weight

Timeframe: Up to approximately Week 40

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

Timeframe: 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

Timeframe: Up to approximately Week 40

Trial details

NCT IDNCT06673069

SponsorIonis Pharmaceuticals, Inc.

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2025-12-03

View on ClinicalTrials.gov More Alzheimer Disease trials

Who can participate

Age range35 Years – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 (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.

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 (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).

What they're measuring

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

Timeframe: Up to approximately Week 40

Number of Participants With Change from Baseline in Laboratory Assessments

Timeframe: Up to approximately Week 40

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

Timeframe: Up to approximately Week 40

Number of Participants With Change From Baseline in Vital Signs

Timeframe: Up to approximately Week 40

Number of Participants With Change From Baseline in Weight

Timeframe: Up to approximately Week 40

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

Timeframe: 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

Timeframe: Up to approximately Week 40