Phase 1 Clinical Trial of Innate Immunity Stimulation Via TLR9 in Early Alzheimer's Disease (AD)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Percentage of Participants with Antineutrophil Cytoplasmic Antibody (ANCA) Confirmed by Autoimmunity Marker Screening Test Result
研究概览
简要总结
This single-center, double-blind, placebo-controlled study will recruit in total 39 participants with either Mild Cognitive Impairment due to Alzheimer's disease (MCI) or Mild Alzheimer's disease dementia (mild AD). There will be 3 Dose levels. An initial cohort of 13 subjects will be randomized to a Dose level 1 (0.1 mg/kg vs. placebo) lasting 8 weeks. An additional 13 subjects will be recruited and randomized into Dose level 2 (0.25 mg/kg vs. placebo) for 8 weeks and 13 subjects for the last Dose level 3 (0.5 mg/kg vs. placebo) for 8 weeks. The primary objective will be to assess safety and tolerability of CpG 1018.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •65-85 years of age
- •MCI due to AD or mild AD dementia per NIA-AA specified criteria published in 2018
- •Montreal Cognitive Assessment (MoCA) score ≥17 AND;
- •Positive Florbetaben PET amyloid scan, or other positive PET amyloid scan performed within one year of study enrollment
- •Must be able to provide consent or assent (If applicable).
- •Must be willing and able to participate in all study related procedures.
- •Must have a reliable study partner to provide information on the subject's cognitive and functional status. Study partner must have sufficient contact with the subject, as determined by the PI, and be available to accompany the subject to clinic visits or by phone.
排除标准
- •History of psychiatric illness (e.g. hallucinations, major depression, suicidal ideation or delusions) that could interfere with completion of study related procedures as determined by PI
- •History of autoimmune disorders or antibody-mediated disease, severe asthma, or other serious infection or systemic illness, as determined by PI
- •Use of corticosteroids or immunosuppressive drugs within 30 days of study entry
- •History of splenectomy
- •Renal impairment
- •Use of chloroquine within 8 weeks of study entry
- •Inability to undergo MRI imaging
- •History of TIA, stroke or seizures within 12 months of screening
- •Any neurological condition other than AD that could contribute to cognitive impairment (including related to possible "long COVID") as determined by PI
- •Participation in any other current AD investigational interventional trial
- •Current use of an anti-coagulant
- •Current use of drugs that are major substrates of cytochrome P450 (CYP) enzyme 1A2
- •Recent exposure to COVID-19 infection within 14 days or recent onset of symptoms within 14 days that may be related to COVID-19 infection
研究组 & 干预措施
CpG 1018 0.1 mg/kg
3 injections at Day 1, Week 4, and Week 8.
Treatment administered as morning injection of dose 0.1mg/kg, followed by 1-hour post-dose observation period to check for injection site reaction and/or adverse reactions.
干预措施: CpG1018 (Drug)
CpG 1018 0.25 mg/kg
3 injections at Day 1, Week 4, and Week 8.
Treatment administered as morning injection of dose 0.25 mg/kg, followed by 1-hour post-dose observation period to check for injection site reaction and/or adverse reactions.
干预措施: CpG1018 (Drug)
CpG 1018 0.5 mg/kg
3 injections at Day 1, Week 4, and Week 8.
Treatment administered as morning injection of dose 0.5 mg/kg, followed by 1-hour post-dose observation period to check for injection site reaction and/or adverse reactions.
干预措施: CpG1018 (Drug)
Placebo
3 injections of sterile saline at Day 1, Week 4, and Week 8, followed by 1-hour post-dose observation period to check for injection site reaction and/or adverse reactions.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants with Antineutrophil Cytoplasmic Antibody (ANCA) Confirmed by Autoimmunity Marker Screening Test Result
时间窗: Up to Week 18
Evaluation of ANCA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
时间窗: Up to Week 14
Evaluation of ARIA-E at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.
Percentage of Participants with Rheumatoid Factor (RF) Confirmed by Autoimmunity Marker Screening Test Result
时间窗: Up to Week 18
Evaluation of RF in patient blood samples at Baseline, Day 56, Week 14 and Week 18.
Percentage of Participants with Antinuclear Antibody (ANA) Confirmed by Autoimmunity Marker Screening Test Result
时间窗: Up to Week 18
Evaluation of ANA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.
Number of Patient-Reported Adverse Events (AEs)
时间窗: Up to Week 18
AEs defined as any symptom, sign, illness or experience that develops or worsens in severity during the course of the study.
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)
时间窗: Up to Week 14
Evaluation of ARIA-H at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.
次要结局
- Change in CSF Tau Biomarker Concentration(Baseline, Week 18)
- Change in AD Assessment Scale Cognitive Subscale (ADAS-Cog-13) Scores(Baseline, Week 18)
- Change in AD Cooperative Study-Activities of Daily Living Inventory, Mild Cognitive Impairment version (ADCS-ADL-MCI) Scores(Baseline, Week 18)
- Change in Montreal Cognitive Assessment (MoCa) Score(Baseline, Week 18)
- Change in Plasma Amyloid Biomarker Concentration(Baseline, Week 18)
- Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores(Baseline, Week 18)
- Change in Global Clinical Dementia Rating (CDR-Global)(Baseline, Week 18)
- Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration(Baseline, Week 18)
- Change in Plasma Tau Biomarker Concentration(Baseline, Week 18)