A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION269 in Adults With Down Syndrome (Hero Study)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 6
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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) ≥
- •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.
排除标准
- •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).
- •Note: Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Cohort 2
Participants will receive a single dose of ION269.
干预措施: ION269 (Drug)
Cohort 3
Participants will receive a single dose of ION269.
干预措施: ION269 (Drug)
Cohort 1
Participants will receive a single dose of ION269.
干预措施: ION269 (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately Week 40
Number of Participants With Change from Baseline in Laboratory Assessments
时间窗: Up to approximately Week 40
Number of Participants With Change from Baseline in Cerebrospinal fluid (CSF) Safety Laboratory Assessments
时间窗: Up to approximately Week 40
Number of Participants With Change From Baseline in Vital Signs
时间窗: Up to approximately Week 40
Number of Participants With Change From Baseline in Weight
时间窗: Up to approximately Week 40
Number of Participants With Change From Baseline in Electrocardiogram (ECG)
时间窗: 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
时间窗: Up to approximately Week 40
Number of Participants With Change From Baseline in Physical and Neurological Examination Findings
时间窗: Up to approximately Week 40
次要结局
- 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)