Skip to main content
OpenTrials
Recruiting

NCT Number: NCT05606341

Innate Immunity Stimulation Via TLR9 in Early AD

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.

Recruiting

Interested in participating?

Request Info

Key information

Age range

60 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

NYU Langone Health

New York, 10016, United States

Location status: Recruiting

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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

Treatment and study plan

CpG1018

Drug

0.1 mg/kg dose administered via subcutaneous injection.

TLR9 agonist supplied by Dynavax Technologies Inc.

Placebo

Drug

Sterile saline injection supplied by the NYU Investigational Pharmacy.

Primary outcomes

  1. Number of Patient-Reported Adverse Events (AEs)

    Time frame: 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.

  2. Percentage of Participants with Rheumatoid Factor (RF) Confirmed by Autoimmunity Marker Screening Test Result

    Time frame: Up to Week 18

    Evaluation of RF in patient blood samples at Baseline, Day 56, Week 14 and Week 18.

  3. Percentage of Participants with Antinuclear Antibody (ANA) Confirmed by Autoimmunity Marker Screening Test Result

    Time frame: Up to Week 18

    Evaluation of ANA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.

  4. Percentage of Participants with Antineutrophil Cytoplasmic Antibody (ANCA) Confirmed by Autoimmunity Marker Screening Test Result

    Time frame: Up to Week 18

    Evaluation of ANCA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.

  5. Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)

    Time frame: Up to Week 14

    Evaluation of ARIA-H at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.

  6. Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)

    Time frame: Up to Week 14

    Evaluation of ARIA-E at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.

Secondary outcomes

  1. Change in AD Assessment Scale Cognitive Subscale (ADAS-Cog-13) Scores

    Time frame: Baseline, Week 18

    13-item self-assessment measuring levels of cognitive and non-cognitive dysfunctions from mild to severe. Total scores range from 0 to 85. Lower scores indicate greater cognitive performance. A decrease in scores indicates cognitive performance improved during the observational period.

  2. Change in AD Cooperative Study-Activities of Daily Living Inventory, Mild Cognitive Impairment version (ADCS-ADL-MCI) Scores

    Time frame: Baseline, Week 18

    18-item questionnaire measuring a participant's basic and instrumental activities of daily living over the previous month. Total scores range from 0-53, where higher scores indicate greater competence in performing activities. An increase in scores indicates competence increased during the observational period.

  3. Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores

    Time frame: Baseline, Week 18

    C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) to 5 (active suicidal ideation with specific plan and intent). A decrease in scores indicates suicidal ideation and behavior decreased during the observational period.

  4. Change in Global Clinical Dementia Rating (CDR-Global)

    Time frame: Baseline, Week 18

    5-point questionnaire assessing six domains of cognitive and functional performance applicable to Alzheimer's disease and related dementias: Memory, Orientation; Judgement & Problem Solving; Community Affairs; Home & Hobbies; and Personal Care. Higher scores indicate greater severity of dementia: 0= Normal, 0.5=very mild dementia, 1=mild dementia, 2=moderate dementia, 3=severe dementia.

  5. Change in Montreal Cognitive Assessment (MoCa) Score

    Time frame: Baseline, Week 18

    30-item assessment of global cognitive function. Total scores range from 0 to 30, with higher scores indicating greater cognitive function. Scores of 26 and higher are consider to be normal. An increase in scores indicates cognitive function increased during the observational period.

  6. Change in Plasma Amyloid Biomarker Concentration

    Time frame: Baseline, Week 18

    Amyloid biomarker concentration detected via plasma analysis.

  7. Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration

    Time frame: Baseline, Week 18

    Amyloid biomarker concentration detected via CSF analysis.

  8. Change in Plasma Tau Biomarker Concentration

    Time frame: Baseline, Week 18

    Tau biomarker concentration detected via plasma analysis.

  9. Change in CSF Tau Biomarker Concentration

    Time frame: Baseline, Week 18

    Tau biomarker concentration detected via CSF analysis.

Study contacts

Contact information is provided by the study sponsor or research team.

Anaztasia Ulysse

CONTACT

[email protected]

212-263-0771

Dylan Nelson

CONTACT

[email protected]

212-263-5845

Sponsors and collaborators

Lead sponsor

NYU Langone Health

Other

Collaborators

  • Alzheimer's Association

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Nov 4, 2022
Registry last updated
Jan 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.