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)

Phase 1

Recruiting

• Conditions: Alzheimer Disease; Down Syndrome
• Interventions: Drug: ION269

• Registration Number: NCT06673069
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

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.

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 Timeline

• Study First Submitted: 2024-10-31
• Study First Submitted QC: 2024-11-01
• Study First Posted: 2024-11-04
• Study Start: 2024-12-20
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-01
• Primary Completion: 2027-02
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1	ION269	Participants will receive a single dose of ION269.
Cohort 2	ION269	Participants will receive a single dose of ION269.
Cohort 3	ION269	Participants will receive a single dose of ION269.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Beta (sAPPβ)	Baseline (Day 1) and Week 36

Trial Locations

Locations (1)

Ionis Investigative Site; 🇪🇸 Barcelona, Spain