Clinical trial NCT05606341: Innate Immunity Stimulation Via TLR9 in Early AD
Official title: Phase 1 Clinical Trial of Innate Immunity Stimulation Via TLR9 in Early Alzheimer's Disease (AD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Mild Cognitive Impairment
Alzheimer Dementia
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: Alzheimer's Association
First posted: 2022-11-04
Enrollment: 15
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Subjects will be randomly allocated in a blinded fashion to receive s.c. injection of either CpG ODN (dose level 1, 0.1 mg/kg) or placebo (saline). Dose escalation will occur after 10 weeks after the last injection in a new subject cohort, and will be based on the safety data and immunostimulatory assessments at previous dose level cohorts.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Patient-Reported Adverse Events (AEs)
timeFrame: Up to Week 18
measure: Percentage of Participants with Rheumatoid Factor (RF) Confirmed by Autoimmunity Marker Screening Test Result
timeFrame: Up to Week 18
measure: Percentage of Participants with Antinuclear Antibody (ANA) Confirmed by Autoimmunity Marker Screening Test Result
timeFrame: Up to Week 18
measure: Percentage of Participants with Antineutrophil Cytoplasmic Antibody (ANCA) Confirmed by Autoimmunity Marker Screening Test Result
timeFrame: Up to Week 18
measure: Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)
timeFrame: Up to Week 14
measure: Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
timeFrame: Up to Week 14
Secondary outcomes:
measure: Change in AD Assessment Scale Cognitive Subscale (ADAS-Cog-13) Scores
timeFrame: Baseline, Week 18
measure: Change in AD Cooperative Study-Activities of Daily Living Inventory, Mild Cognitive Impairment version (ADCS-ADL-MCI) Scores
timeFrame: Baseline, Week 18
measure: Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores
timeFrame: Baseline, Week 18
measure: Change in Global Clinical Dementia Rating (CDR-Global)
timeFrame: Baseline, Week 18
measure: Change in Montreal Cognitive Assessment (MoCa) Score
timeFrame: Baseline, Week 18
measure: Change in Plasma Amyloid Biomarker Concentration
timeFrame: Baseline, Week 18
measure: Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration
timeFrame: Baseline, Week 18
measure: Change in Plasma Tau Biomarker Concentration
timeFrame: Baseline, Week 18
measure: Change in CSF Tau Biomarker Concentration
timeFrame: Baseline, Week 18
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Medical Center
name: Arjun Masurkar, MD
role: PRINCIPAL_INVESTIGATOR
References: