Clinical trial NCT06673069: 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)
Official title: A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION269 in Adults With Down Syndrome (Hero Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Alzheimer Disease
Down Syndrome
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-11-04
Enrollment: 30
Sex: ALL
Minimum age (years): 35
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately Week 40
measure: Number of Participants With Change from Baseline in Laboratory Assessments
timeFrame: Up to approximately Week 40
measure: Number of Participants With Change from Baseline in Cerebrospinal fluid (CSF) Safety Laboratory Assessments
timeFrame: Up to approximately Week 40
measure: Number of Participants With Change From Baseline in Vital Signs
timeFrame: Up to approximately Week 40
measure: Number of Participants With Change From Baseline in Weight
timeFrame: Up to approximately Week 40
measure: Number of Participants With Change From Baseline in Electrocardiogram (ECG)
timeFrame: Up to approximately Week 40
measure: 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
measure: Number of Participants With Change From Baseline in Physical and Neurological Examination Findings
timeFrame: Up to approximately Week 40
Secondary outcomes:
measure: CSF Concentrations of ION269
timeFrame: Pre-dose and post-dose at multiple timepoints up to Week 40
measure: Area Under the Plasma Concentration-time Curve (AUC) of ION269 From Time 0 to Time of Last Measurable Concentration
timeFrame: Pre-dose and post-dose at multiple timepoints up to Week 40
measure: Maximum Observed Plasma Concentration (Cmax) of ION269
timeFrame: Pre-dose and post-dose at multiple timepoints up to Week 40
measure: Time to reach Cmax (Tmax) of ION269
timeFrame: Pre-dose and post-dose at multiple timepoints up to Week 40
measure: Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Alpha (sAPPα)
timeFrame: Baseline (Day 1) and Week 36
measure: Change From Baseline in Concentration of CSF Soluble Amyloid Precursor Protein Beta (sAPPβ)
timeFrame: Baseline (Day 1) and Week 36
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Ionis Investigative Site
state: Indiana
city: Kansas City
country: United States
facility: Ionis Investigative Site
state: Kansas
city: Lexington
country: United States
facility: Ionis Investigative Site
state: Kentucky
city: Saint Louis
country: United States
facility: Ionis Investigative Site
state: Missouri
city: Madison
country: United States
facility: Ionis Investigative Site
state: Wisconsin
city: Barcelona
country: Spain
facility: Ionis Investigative Site
Study officials:
References: