Innate Immunity Stimulation Via TLR9 in Early AD

NYU Langone Health

Status and phase: Enrolling; Phase 1

Conditions: Alzheimer Dementia; Mild Cognitive Impairment

Treatments: Drug: Placebo; Drug: CpG1018

Study type: Interventional

Funder types: Other

Identifiers

NCT05606341

20-00267

Details and patient eligibility

About

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.

Enrollment: 18 estimated patients

Sex: All

Ages: 60 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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18 participants in 4 patient groups, including a placebo group

CpG 1018 0.1 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: CpG1018

Drug: CpG1018

Drug: CpG1018

CpG 1018 0.25 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: CpG1018

Drug: CpG1018

Drug: CpG1018

CpG 1018 0.5 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: CpG1018

Drug: CpG1018

Drug: CpG1018

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo