Innate Immunity Stimulation Via TLR9 in Early AD

Официальное название

Phase 1 Clinical Trial of Innate Immunity Stimulation Via TLR9 in Early Alzheimer's Disease (AD)

Обзор

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.

Вмешательства

• Препарат CpG1018
  0.1 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
• Препарат CpG1018
  0.25 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
• Препарат CpG1018
  0.5 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
• Препарат Placebo
  Sterile saline injection supplied by the NYU Investigational Pharmacy.

Первичные конечные точки

• Number of Patient-Reported Adverse Events (AEs) [Срок оценки: Up to Week 18]
• Percentage of Participants with Rheumatoid Factor (RF) Confirmed by Autoimmunity Marker Screening Test Result [Срок оценки: Up to Week 18]
• Percentage of Participants with Antinuclear Antibody (ANA) Confirmed by Autoimmunity Marker Screening Test Result [Срок оценки: Up to Week 18]
• Percentage of Participants with Antineutrophil Cytoplasmic Antibody (ANCA) Confirmed by Autoimmunity Marker Screening Test Result [Срок оценки: Up to Week 18]
• Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI) [Срок оценки: Up to Week 14]
• Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) [Срок оценки: Up to Week 14]

Вторичные конечные точки (9)

• Change in AD Assessment Scale Cognitive Subscale (ADAS-Cog-13) Scores [Срок оценки: Baseline, Week 18]
• Change in AD Cooperative Study-Activities of Daily Living Inventory, Mild Cognitive Impairment version (ADCS-ADL-MCI) Scores [Срок оценки: Baseline, Week 18]
• Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores [Срок оценки: Baseline, Week 18]
• Change in Global Clinical Dementia Rating (CDR-Global) [Срок оценки: Baseline, Week 18]
• Change in Montreal Cognitive Assessment (MoCa) Score [Срок оценки: Baseline, Week 18]
• Change in Plasma Amyloid Biomarker Concentration [Срок оценки: Baseline, Week 18]
• Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration [Срок оценки: Baseline, Week 18]
• Change in Plasma Tau Biomarker Concentration [Срок оценки: Baseline, Week 18]
• Change in CSF Tau Biomarker Concentration [Срок оценки: Baseline, Week 18]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• NYU Langone Health — New York

Идентификаторы

NCT: NCT05606341 · 20-00267

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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