Recruiting
Phase 1

TLR9 in AD

Sponsor:

NYU Langone Health

Code:

NCT05606341

Conditions

Mild Cognitive Impairment

Alzheimer Dementia

Eligibility Criteria

Sex: All

Age: 60 - 70+

Healthy Volunteers: Not accepted

Interventions

CpG1018

CpG1018

CpG1018

Placebo

Study Details

Brief summary:

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.

Conditions

Mild Cognitive Impairment

Alzheimer Dementia

Study ID

NCT05606341

Start date

Mar 13, 2023

Status verified date

Jan, 2026

Completion date

Nov, 2026

Anticipated

Primary completion date

Nov, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 60 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. 65-85 years of age
2. MCI due to AD or mild AD dementia per NIA-AA specified criteria published in 2018
3. Montreal Cognitive Assessment (MoCA) score ≥17 AND;
4. Positive Florbetaben PET amyloid scan, or other positive PET amyloid scan performed within one year of study enrollment
5. Must be able to provide consent or assent (If applicable).
6. Must be willing and able to participate in all study related procedures.
7. 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:

1. 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
2. History of autoimmune disorders or antibody-mediated disease, severe asthma, or other serious infection or systemic illness, as determined by PI
3. Use of corticosteroids or immunosuppressive drugs within 30 days of study entry
4. History of splenectomy
5. Renal impairment
6. Use of chloroquine within 8 weeks of study entry
7. Inability to undergo MRI imaging
8. History of TIA, stroke or seizures within 12 months of screening
9. Any neurological condition other than AD that could contribute to cognitive impairment (including related to possible "long COVID") as determined by PI
10. Participation in any other current AD investigational interventional trial
11. Current use of an anti-coagulant
12. Current use of drugs that are major substrates of cytochrome P450 (CYP) enzyme 1A2
13. 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

Study Design

Enrollment

18 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

placebo comparator: 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.

Interventions

CpG1018

0.1 mg/kg dose administered via subcutaneous injection.

TLR9 agonist supplied by Dynavax Technologies Inc.

CpG1018

0.25 mg/kg dose administered via subcutaneous injection.

TLR9 agonist supplied by Dynavax Technologies Inc.

CpG1018

0.5 mg/kg dose administered via subcutaneous injection.

TLR9 agonist supplied by Dynavax Technologies Inc.

Placebo

Sterile saline injection supplied by the NYU Investigational Pharmacy.

Primary outcome measure

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

Central Contacts and Locations

Locations

NYU Langone Health

Recruiting

New York, New York, United States, 10016

More Information

Sponsor

NYU Langone Health

Last update posted

Jan 7, 2026

Last verified

Jan, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by NYU Langone Health on 2026-01-07.