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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1
Administered as intrathecal (IT) injection.
Ionis Investigative Site
Indianapolis, Indiana, United States
Ionis Investigative Site
Kansas City, Kansas, United States
Ionis Investigative Site
Lexington, Kentucky, United States
Ionis Investigative Site
St Louis, Missouri, United States
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
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
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Ionis Investigative Site
Madison, Wisconsin, United States
Ionis Investigative Site
Barcelona, Spain
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