Innate Immunity Stimulation Via TLR9 in Early AD

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

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment; Alzheimer Dementia
• Intervention / Treatment: Drug: CpG1018; Drug: CpG1018; Drug: CpG1018; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Anaztasia Ulysse; Phone Number: 212-263-0771; Email: ADClinicalTrials@nyulangone.org
• Study Contact Backup: Name: Dylan Nelson; Phone Number: 212-263-5845; Email: dylan.nelson@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: CpG1018; 0.1 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.; Drug: CpG1018; 0.25 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.; Drug: CpG1018; 0.5 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
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.	Drug: CpG1018; 0.1 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.; Drug: CpG1018; 0.25 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.; Drug: CpG1018; 0.5 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
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.	Drug: CpG1018; 0.1 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.; Drug: CpG1018; 0.25 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.; Drug: CpG1018; 0.5 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
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.	Drug: Placebo; Sterile saline injection supplied by the NYU Investigational Pharmacy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patient-Reported Adverse Events (AEs)	AEs defined as any symptom, sign, illness or experience that develops or worsens in severity during the course of the study.	Up to Week 18
Percentage of Participants with Rheumatoid Factor (RF) Confirmed by Autoimmunity Marker Screening Test Result	Evaluation of RF in patient blood samples at Baseline, Day 56, Week 14 and Week 18.	Up to Week 18
Percentage of Participants with Antinuclear Antibody (ANA) Confirmed by Autoimmunity Marker Screening Test Result	Evaluation of ANA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.	Up to Week 18
Percentage of Participants with Antineutrophil Cytoplasmic Antibody (ANCA) Confirmed by Autoimmunity Marker Screening Test Result	Evaluation of ANCA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.	Up to Week 18
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)	Evaluation of ARIA-H at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.	Up to Week 14
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)	Evaluation of ARIA-E at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.	Up to Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in AD Assessment Scale Cognitive Subscale (ADAS-Cog-13) Scores	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.	Baseline, Week 18
Change in AD Cooperative Study-Activities of Daily Living Inventory, Mild Cognitive Impairment version (ADCS-ADL-MCI) Scores	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.	Baseline, Week 18
Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores	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.	Baseline, Week 18
Change in Global Clinical Dementia Rating (CDR-Global)	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.	Baseline, Week 18
Change in Montreal Cognitive Assessment (MoCa) Score	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.	Baseline, Week 18
Change in Plasma Amyloid Biomarker Concentration	Amyloid biomarker concentration detected via plasma analysis.	Baseline, Week 18
Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration	Amyloid biomarker concentration detected via CSF analysis.	Baseline, Week 18
Change in Plasma Tau Biomarker Concentration	Tau biomarker concentration detected via plasma analysis.	Baseline, Week 18
Change in CSF Tau Biomarker Concentration	Tau biomarker concentration detected via CSF analysis.	Baseline, Week 18

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Alzheimer's Association
• Investigators: Principal Investigator: Arjun Masurkar, MD, NYU Langone Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Estimated): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic; 1018 oligonucleotide
• Other Study ID Numbers: 20-00267

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Alok.Vedvyas@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to Alok.Vedvyas@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No