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Innate Immunity Stimulation Via TLR9 in Early AD

Primary Purpose

Mild Cognitive Impairment, Alzheimer Dementia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CpG1018
CpG1018
CpG1018
Placebo
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mild Cognitive Impairment

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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

Sites / Locations

  • NYU Langone HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

CpG 1018 0.1 mg/kg

CpG 1018 0.25 mg/kg

CpG 1018 0.5 mg/kg

Placebo

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
Change in Plasma Amyloid Biomarker Concentration
Amyloid biomarker concentration detected via plasma analysis.
Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration
Amyloid biomarker concentration detected via CSF analysis.
Change in Plasma Tau Biomarker Concentration
Tau biomarker concentration detected via plasma analysis.
Change in CSF Tau Biomarker Concentration
Tau biomarker concentration detected via CSF analysis.

Full Information

First Posted
November 1, 2022
Last Updated
April 10, 2023
Sponsor
NYU Langone Health
Collaborators
Alzheimer's Association
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1. Study Identification

Unique Protocol Identification Number
NCT05606341
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 13, 2023 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
Alzheimer's Association

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment, Alzheimer Dementia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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
ParticipantInvestigator
Allocation
Randomized
Enrollment
39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CpG 1018 0.1 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
CpG 1018 0.25 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
CpG 1018 0.5 mg/kg
Arm Type
Experimental
Arm 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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
CpG1018
Intervention Description
0.1 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
Intervention Type
Drug
Intervention Name(s)
CpG1018
Intervention Description
0.25 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
Intervention Type
Drug
Intervention Name(s)
CpG1018
Intervention Description
0.5 mg/kg dose administered via subcutaneous injection. TLR9 agonist supplied by Dynavax Technologies Inc.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Sterile saline injection supplied by the NYU Investigational Pharmacy.
Primary Outcome Measure Information:
Title
Number of Patient-Reported Adverse Events (AEs)
Description
AEs defined as any symptom, sign, illness or experience that develops or worsens in severity during the course of the study.
Time Frame
Up to Week 18
Title
Percentage of Participants with Rheumatoid Factor (RF) Confirmed by Autoimmunity Marker Screening Test Result
Description
Evaluation of RF in patient blood samples at Baseline, Day 56, Week 14 and Week 18.
Time Frame
Up to Week 18
Title
Percentage of Participants with Antinuclear Antibody (ANA) Confirmed by Autoimmunity Marker Screening Test Result
Description
Evaluation of ANA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.
Time Frame
Up to Week 18
Title
Percentage of Participants with Antineutrophil Cytoplasmic Antibody (ANCA) Confirmed by Autoimmunity Marker Screening Test Result
Description
Evaluation of ANCA in patient blood samples at Baseline, Day 56, Week 14 and Week 18.
Time Frame
Up to Week 18
Title
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)
Description
Evaluation of ARIA-H at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.
Time Frame
Up to Week 14
Title
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
Description
Evaluation of ARIA-E at Baseline and Week 14 using 3T PET/MR Siemens Biograph system.
Time Frame
Up to Week 14
Secondary Outcome Measure Information:
Title
Change in AD Assessment Scale Cognitive Subscale (ADAS-Cog-13) Scores
Description
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.
Time Frame
Baseline, Week 18
Title
Change in AD Cooperative Study-Activities of Daily Living Inventory, Mild Cognitive Impairment version (ADCS-ADL-MCI) Scores
Description
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.
Time Frame
Baseline, Week 18
Title
Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores
Description
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.
Time Frame
Baseline, Week 18
Title
Change in Global Clinical Dementia Rating (CDR-Global)
Description
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.
Time Frame
Baseline, Week 18
Title
Change in Montreal Cognitive Assessment (MoCa) Score
Description
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.
Time Frame
Baseline, Week 18
Title
Change in Plasma Amyloid Biomarker Concentration
Description
Amyloid biomarker concentration detected via plasma analysis.
Time Frame
Baseline, Week 18
Title
Change in Cerebral Spinal Fluid (CSF) Amyloid Biomarker Concentration
Description
Amyloid biomarker concentration detected via CSF analysis.
Time Frame
Baseline, Week 18
Title
Change in Plasma Tau Biomarker Concentration
Description
Tau biomarker concentration detected via plasma analysis.
Time Frame
Baseline, Week 18
Title
Change in CSF Tau Biomarker Concentration
Description
Tau biomarker concentration detected via CSF analysis.
Time Frame
Baseline, Week 18

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alok Vedvyas
Phone
212-263-2048
Email
Alok.Vedvyas@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arjun Masurkar, MD
Organizational Affiliation
NYU Langone Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

Innate Immunity Stimulation Via TLR9 in Early AD

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