Mild Cognitive ImpairmentPhase 1NCT05606341
Innate Immunity Stimulation Via TLR9 in Early AD
A Phase 1 study testing CpG1018 in people with Mild Cognitive Impairment and Alzheimer Dementia, run by NYU Langone Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Dementia
- What is being tested?
- CpG1018
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2023to Nov 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 65-85 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.
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
NYU Langone Health
New York, New York, 10016
About this study
Official title: 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.
- Conditions
- Mild Cognitive Impairment, Alzheimer Dementia
- Being tested
- CpG1018, Placebo
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CpG1018Drug
0.1 mg/kg dose administered via subcutaneous injection.
TLR9 agonist supplied by Dynavax Technologies Inc.
CpG1018Drug
0.25 mg/kg dose administered via subcutaneous injection.
TLR9 agonist supplied by Dynavax Technologies Inc.
CpG1018Drug
0.5 mg/kg dose administered via subcutaneous injection.
TLR9 agonist supplied by Dynavax Technologies Inc.
PlaceboDrug
Sterile saline injection supplied by the NYU Investigational Pharmacy.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to Week 14
Secondary outcomes (9)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 18
Change in Plasma Amyloid Biomarker Concentration
Amyloid biomarker concentration detected via plasma analysis.
Measured: Baseline, Week 18
Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration
Amyloid biomarker concentration detected via CSF analysis.
Measured: Baseline, Week 18
Change in Plasma Tau Biomarker Concentration
Tau biomarker concentration detected via plasma analysis.
Measured: Baseline, Week 18
Change in CSF Tau Biomarker Concentration
Tau biomarker concentration detected via CSF analysis.
Measured: Baseline, Week 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2022
- Study start13 Mar 2023
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Alzheimer's Association
- Responsible party
- Sponsor
- Investigators
- Arjun Masurkar, MD, Principal investigator, NYU Langone Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05606341
- Sponsor's protocol ID
- 20-00267
- Status last verified
- Jan 2026
- First submitted
- 1 Nov 2022
- Last updated
- 7 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Clinical Trial of Innate Immunity Stimulation Via TLR9 in Early Alzheimer's Disease (AD)
- ClinicalTrials.gov ID
- NCT05606341
- Acronym / sponsor ID
- 20-00267
- Conditions
- Mild Cognitive Impairment, Alzheimer Dementia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Alzheimer's Association
- Study start
- 13 Mar 2023 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 4 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| CpG 1018 0.1 mg/kg | Experimental | Drug: CpG10183 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. |
| CpG 1018 0.25 mg/kg | Experimental | Drug: CpG10183 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. |
| CpG 1018 0.5 mg/kg | Experimental | Drug: CpG10183 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 | Placebo comparator | Drug: Placebo3 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. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 65-85 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).
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CpG10180.1 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc. | Drug | CpG 1018 0.1 mg/kg |
| CpG10180.25 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc. | Drug | CpG 1018 0.25 mg/kg |
| CpG10180.5 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc. | Drug | CpG 1018 0.5 mg/kg |
| PlaceboSterile saline injection supplied by the NYU Investigational Pharmacy. | Drug | Placebo |
Primary outcome
Number of Patient-Reported Adverse Events (AEs)
Time frame: Up to Week 18
AEs defined as any symptom, sign, illness or experience that develops or worsens in severity during the course of the study.
Percentage of Participants with Rheumatoid Factor (RF) Confirmed by Autoimmunity Marker Screening Test Result
Time frame: Up to Week 18
Evaluation of RF in patient blood samples at Baseline, Day 56, Week 14 and Week 18.
Percentage of Participants with Antinuclear Antibody (ANA) Confirmed by Autoimmunity Marker Screening Test Result
Time frame: Up to Week 18
Evaluation of ANA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.
Percentage of Participants with Antineutrophil Cytoplasmic Antibody (ANCA) Confirmed by Autoimmunity Marker Screening Test Result
Time frame: Up to Week 18
Evaluation of ANCA in patient blood samples at Baseline, Day 56, Week 14 and 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
Evaluation of ARIA-H at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
Time frame: Up to Week 14
Evaluation of ARIA-E at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.
9 secondary outcomes
Change in AD Assessment Scale Cognitive Subscale (ADAS-Cog-13) Scores
Time frame: Baseline, Week 18
Change in AD Cooperative Study-Activities of Daily Living Inventory, Mild Cognitive Impairment version (ADCS-ADL-MCI) Scores
Time frame: Baseline, Week 18
Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores
Time frame: Baseline, Week 18
Change in Global Clinical Dementia Rating (CDR-Global)
Time frame: Baseline, Week 18
Change in Montreal Cognitive Assessment (MoCa) Score
Time frame: Baseline, Week 18
Change in Plasma Amyloid Biomarker Concentration
Time frame: Baseline, Week 18
Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration
Time frame: Baseline, Week 18
Change in Plasma Tau Biomarker Concentration
Time frame: Baseline, Week 18
Change in CSF Tau Biomarker Concentration
Time frame: Baseline, Week 18
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Arjun Masurkar, MD principal investigator
NYU Langone Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CpG1018 in people with Mild Cognitive Impairment and Alzheimer Dementia, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anaztasia Ulysse (212-263-0771, ADClinicalTrials@nyulangone.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patient-Reported Adverse Events (AEs) (time frame: Up to Week 18). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2026.