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Evaluation of Tau Protein in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants

Primary Purpose

Alzheimer Disease

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
[18F]MNI-1020
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Alzheimer Disease

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

All Participants

  • Female participants must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year. Male participants and their partners of childbearing potential must commit to the use of two methods of contraception, one of which is a barrier method for male participants for the study duration
  • Male participants must not donate sperm during the study and for 3 months after completion

Healthy Participants

  • Males and females aged greater than or equal 50 years. Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the [18F]molecular neuroimaging (MNI)-1020 imaging visit
  • Have screening [18F]florbetapir positron emission tomography (PET) imaging demonstrating no significant amyloid binding based on qualitative analysis (visual read)

Alzheimer Disease - Have screening [18F]florbetapir or prior amyloid (in the last 12 months) PET imaging demonstrating amyloid binding based on qualitative (visual read)

Exclusion Criteria:

All Participants

  • Prior participation in other research protocols or clinical care in the last year in addition to the radiation exposure expected from participation in this clinical study, such that radiation exposure exceeds the effective dose of 50 millisievert (mSv), which would be above the acceptable annual limit established by the United States Federal Guidelines
  • Unsuitable veins for repeated venipuncture
  • Magnetic resonance imaging exclusion criteria include: evidence of cerebrovascular disease (more than two lacunar infarcts, any territorial infarct greater than 1 centimeter 3, or deep white matter abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent hyperintense lesion on the FLAIR sequence that is greater than or equal to 20 millimeter (mm) in any dimension), infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with central nervous system disease
  • Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, central nervous system aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in Magnetic Resonance Imaging (MRI)

Alzheimer Disease

- Has received treatment that targeted amyloid beta or tau within the last 3 months

Sites / Locations

  • Invicro

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

[18F]MNI-1020

Arm Description

Participants will receive a single intravenous bolus injection of [18F]MNI-1020 at a dose of not more than 10 millicurie (mCi), with a maximum mass dose of 10 microgram (mcg) and maximum volume of 10 milliliter (mL) at imaging visit.

Outcomes

Primary Outcome Measures

Standardized Uptake Value Ratio (SUVR) of [18F]MNI-1020
Tracer uptake will be expressed in Standardized Uptake Value Ratio (SUVR). Regions used for tracer uptake quantitation will include cortical regions (frontal cortex, posterior cingulate, lateral temporal cortex, parietal cortex, occipital cortex, mesial temporal cortex, inferior temporal cortex, hippocampus, and anterior cingulate). Subcortical regions (basal ganglia, substantia nigra, choroid plexus) will be used for detection of possible off-target binding. Regions predicted to be free of tau pathology will be used as reference (cerebellum and pons). SUVR will be calculated as SUV target/SUV reference region (e.g., cerebellar gray).
Plasma Concentration of 18F]MNI-1020 in AD Participants Compared With age Matched Healthy Participants
Pharmacokinetics of [18F]MNI-1020 will be assessed by using plasma concentration data and compared in participants with probable Alzheimer's disease (AD) and age matched healthy participants.
Number of Participants With Adverse Events
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Distribution of tau (Using [18F]MNI-1020) Compared to Amyloid Beta (Using Florbetapir) in Participants With Probable AD
Within the AD participants, the distribution and binding of [18F]florbetapir will be compared to the [18F]MNI-1020 binding across multiple regions. This will be done by visual reading of scans, with amyloid signal predicted to be high in frontal cortical regions in participants with probable AD and absent from cortex in healthy participants, while tau signal is predicted to be present in hippocampus and entorhinal cortex in healthy elderly participants, and in medial and lateral temporal cortex in participants with probable AD. Semi-quantitative analysis will also be conducted comparing SUVR of the tracers in these same regions, using cerebellum as reference.

Secondary Outcome Measures

Full Information

First Posted
August 2, 2017
Last Updated
August 17, 2022
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03239561
Brief Title
Evaluation of Tau Protein in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants
Official Title
Phase 0 Exploratory Study of [18F]MNI-1020 (Also Known as [18F]JNJ-64326067) as an Imaging Marker for Tau Protein in the Brain of Subjects With Alzheimer's Disease Compared to Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
September 6, 2017 (Actual)
Primary Completion Date
April 30, 2018 (Actual)
Study Completion Date
April 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

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

5. Study Description

Brief Summary
The primary objectives of this study are to characterize [18F]molecular neuroimaging (MNI)-1020, a positron emission tomography (PET) radioligand for imaging tau pathology, to visually and quantitatively assess and compare brain uptake and pharmacokinetics of [18F]MNI-1020 in participants with probable Alzheimer's disease (AD) and compare with age matched healthy participants, to evaluate the safety of a single injection of [18F]MNI-1020 and to compare the distribution of tau (using [18F]MNI-1020) and amyloid beta (using florbetapir) in participants with probable AD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
[18F]MNI-1020
Arm Type
Experimental
Arm Description
Participants will receive a single intravenous bolus injection of [18F]MNI-1020 at a dose of not more than 10 millicurie (mCi), with a maximum mass dose of 10 microgram (mcg) and maximum volume of 10 milliliter (mL) at imaging visit.
Intervention Type
Drug
Intervention Name(s)
[18F]MNI-1020
Other Intervention Name(s)
[18F]JNJ-64326067
Intervention Description
Participants will receive a single intravenous bolus injection of [18F]MNI-1020 at a dose of not more than 10 millicurie (mCi), with a maximum mass dose of 10 microgram (mcg) and maximum volume of 10 milliliter (mL) at imaging visit.
Primary Outcome Measure Information:
Title
Standardized Uptake Value Ratio (SUVR) of [18F]MNI-1020
Description
Tracer uptake will be expressed in Standardized Uptake Value Ratio (SUVR). Regions used for tracer uptake quantitation will include cortical regions (frontal cortex, posterior cingulate, lateral temporal cortex, parietal cortex, occipital cortex, mesial temporal cortex, inferior temporal cortex, hippocampus, and anterior cingulate). Subcortical regions (basal ganglia, substantia nigra, choroid plexus) will be used for detection of possible off-target binding. Regions predicted to be free of tau pathology will be used as reference (cerebellum and pons). SUVR will be calculated as SUV target/SUV reference region (e.g., cerebellar gray).
Time Frame
Up to 180 minutes after tracer injection on Day 1
Title
Plasma Concentration of 18F]MNI-1020 in AD Participants Compared With age Matched Healthy Participants
Description
Pharmacokinetics of [18F]MNI-1020 will be assessed by using plasma concentration data and compared in participants with probable Alzheimer's disease (AD) and age matched healthy participants.
Time Frame
Pre-injection, 5, 10, 30, and 60 minutes post-injection
Title
Number of Participants With Adverse Events
Description
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time Frame
Baseline up to Follow-Up (Day 4)
Title
Distribution of tau (Using [18F]MNI-1020) Compared to Amyloid Beta (Using Florbetapir) in Participants With Probable AD
Description
Within the AD participants, the distribution and binding of [18F]florbetapir will be compared to the [18F]MNI-1020 binding across multiple regions. This will be done by visual reading of scans, with amyloid signal predicted to be high in frontal cortical regions in participants with probable AD and absent from cortex in healthy participants, while tau signal is predicted to be present in hippocampus and entorhinal cortex in healthy elderly participants, and in medial and lateral temporal cortex in participants with probable AD. Semi-quantitative analysis will also be conducted comparing SUVR of the tracers in these same regions, using cerebellum as reference.
Time Frame
Screening for Florbetapir; Day 1 for [18F]MNI-1020

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: All Participants Female participants must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year. Male participants and their partners of childbearing potential must commit to the use of two methods of contraception, one of which is a barrier method for male participants for the study duration Male participants must not donate sperm during the study and for 3 months after completion Healthy Participants Males and females aged greater than or equal 50 years. Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the [18F]molecular neuroimaging (MNI)-1020 imaging visit Have screening [18F]florbetapir positron emission tomography (PET) imaging demonstrating no significant amyloid binding based on qualitative analysis (visual read) Alzheimer Disease - Have screening [18F]florbetapir or prior amyloid (in the last 12 months) PET imaging demonstrating amyloid binding based on qualitative (visual read) Exclusion Criteria: All Participants Prior participation in other research protocols or clinical care in the last year in addition to the radiation exposure expected from participation in this clinical study, such that radiation exposure exceeds the effective dose of 50 millisievert (mSv), which would be above the acceptable annual limit established by the United States Federal Guidelines Unsuitable veins for repeated venipuncture Magnetic resonance imaging exclusion criteria include: evidence of cerebrovascular disease (more than two lacunar infarcts, any territorial infarct greater than 1 centimeter 3, or deep white matter abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent hyperintense lesion on the FLAIR sequence that is greater than or equal to 20 millimeter (mm) in any dimension), infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with central nervous system disease Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, central nervous system aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in Magnetic Resonance Imaging (MRI) Alzheimer Disease - Has received treatment that targeted amyloid beta or tau within the last 3 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Invicro
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States

12. IPD Sharing Statement

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Evaluation of Tau Protein in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants

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