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)

NCT06673069 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: ION269-CS12023-509257-31-00U1111-1306-9498
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 6

Brief 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.

Conditions

Alzheimer Disease; Down Syndrome

Outcome Measures

Primary Outcomes (8)

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

  Up to approximately Week 40

• Number of Participants With Change from Baseline in Laboratory Assessments

  Up to approximately Week 40

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

  Up to approximately Week 40

• Number of Participants With Change From Baseline in Vital Signs

  Up to approximately Week 40

• Number of Participants With Change From Baseline in Weight

  Up to approximately Week 40

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

  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

  Up to approximately Week 40

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

  Up to approximately Week 40

Secondary Outcomes (6)

• CSF Concentrations of ION269

  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

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

• Maximum Observed Plasma Concentration (Cmax) of ION269

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

• Time to reach Cmax (Tmax) of ION269

  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)

  Baseline (Day 1) and Week 36

Study Arms (3)

Cohort 1

EXPERIMENTAL

Participants will receive a single dose of ION269.

Drug: ION269

Cohort 2

EXPERIMENTAL

Participants will receive a single dose of ION269.

Drug: ION269

Cohort 3

EXPERIMENTAL

Participants will receive a single dose of ION269.

Drug: ION269

Interventions

ION269 DRUG

Administered as intrathecal (IT) injection.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 35 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (6)

Ionis Investigative Site

Indianapolis, Indiana, 46202, United States

Location

Ionis Investigative Site

Kansas City, Kansas, 66205, United States

Location

Ionis Investigative Site

Lexington, Kentucky, 40536, United States

Location

Ionis Investigative Site

St Louis, Missouri, 63110, United States

Location

Ionis Investigative Site

Madison, Wisconsin, 53705, United States

Location

Ionis Investigative Site

Barcelona, 08041, Spain

Location

MeSH Terms

Conditions

Alzheimer Disease; Down Syndrome

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 4, 2024
• Study Start: December 20, 2024
• Primary Completion: December 3, 2025
• Study Completion: December 3, 2025
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (5); ES (1)