Innate Immunity Stimulation Via TLR9 in Early AD

NCT05606341 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-00267
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (9)

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

  Baseline, Week 18

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

  Baseline, Week 18

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

  Baseline, Week 18

• Change in Global Clinical Dementia Rating (CDR-Global)

  Baseline, Week 18

• Change in Montreal Cognitive Assessment (MoCa) Score

  Baseline, Week 18

Study Arms (4)

CpG 1018 0.1 mg/kg

EXPERIMENTAL

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

CpG 1018 0.25 mg/kg

EXPERIMENTAL

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

CpG 1018 0.5 mg/kg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

CpG1018 DRUG

0.1 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.

CpG 1018 0.1 mg/kg

Placebo DRUG

Sterile saline injection supplied by the NYU Investigational Pharmacy.

Placebo

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• Alzheimer's Association: collaborator

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

1018 oligonucleotide

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Arjun Masurkar, MD

  NYU Langone Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anaztasia Ulysse

CONTACT

212-263-0771; ADClinicalTrials@nyulangone.org

Dylan Nelson

CONTACT

212-263-5845; dylan.nelson@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 4, 2022
• Study Start: March 13, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (1)