Alzheimer DiseaseEarly Phase 1NCT03071224
Phase 1 Evaluation of [18F]MK-6240 PET as an Imaging Marker for Tau Protein
A Early Phase 1 study testing [18F] MNI-946 and [18F]Florbetapir in people with Alzheimer Disease and Healthy Volunteers, run by Invicro at 1 site in United States.
Trial summary
The overall goal of this protocol is to evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Healthy Volunteers
- What is being tested?
- [18F] MNI-946 and [18F]Florbetapir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to 9 Jun 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- Female subjects 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 or, if they are of child-bearing potential, must commit to use two methods of contraception, one of which is a barrier method for the duration of the study.
- Male subjects 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 subjects for the study duration.
- Male subjects must not donate sperm for the study duration.
- Willing and able to cooperate with study procedures.
- Inclusion criteria for healthy volunteer subjects (all cohorts):
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- Males and females aged ≥50 years. Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the [18F]MK-6240 imaging visit.
- No cognitive impairment from neuropsychological battery as judged by the investigator
- Have screening [18F]Florbetapir PET imaging demonstrating no significant amyloid binding based on qualitative (visual read).
- No family history of Alzheimer's disease or neurological disease associated with dementia
- Have a CDR global score=0
- Have an MMSE score ≥28
- Willing and able to cooperate with study procedures.
- Inclusion criteria for subjects with a diagnosis of probable Alzheimer's disease (AD) all cohorts:
- Males and females aged 50 to 80 years.
- Have probable Alzheimer's disease dementia, based on the NINCDS/ADRDA and DSM-IV criteria, with mild severity and amnestic presentation
- Have a CDR score ≥ 0.5 at screening
- Have a MMSE score between ≤26 .
- Have screening [18F]Florbetapir or prior (in the last 12 months) amyloid PET imaging demonstrating amyloid binding based on qualitative (visual read).[18F]Florbetapir PET imaging results will be shared with participants and scans may be used by participants for future research use.
- A brain MRI that supports a diagnosis of AD, with no evidence of significant neurologic pathology.
- Medications taken for symptomatic treatment of AD must be maintained on a stable dosage regimen for at least 30 days before screening visit.
- Signed and dated written informed consent obtained from the subject and the subject's legally authorized representative or caregiver (if applicable).
- The subject has an appropriate caregiver capable of accompanying subject on all visits, if necessary.
- Subjects must be active smokers at the time of initial consent
Who cannot join
- Current or prior history of any alcohol or drug abuse.
- Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness.
- Subject has received an investigational therapeutic drug or device within 30 days of screening.
- 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 mSv, which would be above the acceptable annual limit established by the US Federal Guidelines.
- Pregnancy, lactating or breastfeeding.
- Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease.
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- Unsuitable veins for repeated venipuncture.
- MRI exclusion criteria include: Findings that may be responsible for the neurologic status of the subject such as significant evidence of cerebrovascular disease (more than two lacunar infarcts, any territorial infarct >1cm3, 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 ≥20 mm in any dimension), infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with CNS disease.
- Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI.
- Has received treatment that targeted Aβ or tau within the last 3 months.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 Evaluation of [18F]MK-6240 PET as an Imaging Marker for Tau Protein in the Brain of Patients With Alzheimer's Disease Compared to Healthy Volunteers
The overall goal of this protocol is to evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical.
Read the detailed description
The overall goal of this protocol is to evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical.
- To measure the dynamic uptake and washout of [18F]MK-6240 in brain using positron emission tomography (PET) in patients with Alzheimer's disease and healthy volunteers.
- To measure blood metabolites of [18F]MK-6240 and perform kinetic modeling to assess its ability to measure tau protein in brain using the tracer plasma concentration or a reference region as indirect input.
- To obtain test/retest reliability of the tracer binding parameters in patients with Alzheimer's disease and healthy volunteers (Cohort 1).
- To acquire safety data following injection of [18F]MK-6240.
- To determine the longitudinal change in tau burden (including SUVR and tau distribution metrics) compared to baseline in AD subjects and in similarly aged HV subjects.
- To evaluate the correlation between the longitudinal change in tau burden and change in clinical, MRI and CSF biomarker measures in AD subjects and in similarly-aged HV subjects.
- To further explore the relationship between tracer metabolism and smoking (Cohort 3).
- Conditions
- Alzheimer Disease, Healthy Volunteers
- Being tested
- [18F] MNI-946, [18F]Florbetapir
- Keywords
- AD, HV
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F] MNI-946Drug
Also called [18F]MK6240
Subjects will undergo PET imaging using [18F]MNI-946, a PET radioligand for imaging tau.
[18F]FlorbetapirDrug
Subjects with Alzheimer's disease will receive a [18F]florbetapir scan to compare distribution of tau in the brain compared to that of [18F]MNI-946.
| Study group | Role | What they receive |
|---|---|---|
| [18F]MNI-946 | Experimental | To evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical. Receives: Drug: [18F] MNI-946; Drug: [18F]Florbetapir |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the longitudinal change in tau burden (including SUVR and tau distribution metrics) compared to baseline in AD subjects and in similarly aged HV subjects.
Tracer uptake will be evaluated in regions of interest for analysis of regional [18F]MK-6240 binding/uptake and expressed in SUV by using established methods for normalization for 12 AD and 3 HV subjects in Cohort 1, 8 AD and 2 HV subjects in Cohort 2, and 3 AD and 3 HV subjects in Cohort 3. Target regions of interest in the standard volume of interest (VOI) template, will be used for tracer uptake quantitation of potentially increased binding to tau pathology will correspond in particular to the cortical regions of the brain. Descriptive statistics will be applied to describe the tau deposition by region as measured by [18F]MK-6240.
Descriptive statistics will be applied to describe the tau deposition by region as measured by [18F]MNI-946.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2017
- Study startJun 2016
- Primary completion9 Jun 2021
- Study completion9 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Invicro
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Russell, M.D., Ph. D, Principal investigator, Invicro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03071224
- Sponsor's protocol ID
- [18F] MNI-946
- Status last verified
- Sep 2019
- First submitted
- 28 Feb 2017
- Last updated
- 14 Jun 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Evaluation of [18F]MK-6240 PET as an Imaging Marker for Tau Protein in the Brain of Patients With Alzheimer's Disease Compared to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03071224
- Acronym / sponsor ID
- [18F] MNI-946
- Conditions
- Alzheimer Disease, Healthy Volunteers
- Keywords
- AD, HV
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- InvicroUniversity, hospital or other
- Study start
- Jun 2016 (actual)
- Primary completion
- 9 Jun 2021 (actual)
- Study completion
- 9 Jun 2021 (actual)
- First posted
- 6 Mar 2017 (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.
The overall goal of this protocol is to evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical.
Detailed description
The overall goal of this protocol is to evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical.
- To measure the dynamic uptake and washout of [18F]MK-6240 in brain using positron emission tomography (PET) in patients with Alzheimer's disease and healthy volunteers.
- To measure blood metabolites of [18F]MK-6240 and perform kinetic modeling to assess its ability to measure tau protein in brain using the tracer plasma concentration or a reference region as indirect input.
- To obtain test/retest reliability of the tracer binding parameters in patients with Alzheimer's disease and healthy volunteers (Cohort 1).
- To acquire safety data following injection of [18F]MK-6240.
- To determine the longitudinal change in tau burden (including SUVR and tau distribution metrics) compared to baseline in AD subjects and in similarly aged HV subjects.
- To evaluate the correlation between the longitudinal change in tau burden and change in clinical, MRI and CSF biomarker measures in AD subjects and in similarly-aged HV subjects.
- To further explore the relationship between tracer metabolism and smoking (Cohort 3).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [18F]MNI-946 | Experimental | Drug: [18F] MNI-946, Drug: [18F]FlorbetapirTo evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Written informed consent must be obtained before any assessment is performed.
- Female subjects 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 or, if they are of child-bearing potential, must commit to use two methods of contraception, one of which is a barrier method for the duration of the study.
- Male subjects 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 subjects for the study duration.
- Male subjects must not donate sperm for the study duration.
- Willing and able to cooperate with study procedures.
Key exclusion criteria (10 listed)
- Current or prior history of any alcohol or drug abuse.
- Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness.
- Subject has received an investigational therapeutic drug or device within 30 days of screening.
- 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 mSv, which would be above the acceptable annual limit established by the US Federal Guidelines.
- Pregnancy, lactating or breastfeeding.
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 |
|---|---|---|
| [18F] MNI-946Also: [18F]MK6240Subjects will undergo PET imaging using [18F]MNI-946, a PET radioligand for imaging tau. | Drug | [18F]MNI-946 |
| [18F]FlorbetapirSubjects with Alzheimer's disease will receive a [18F]florbetapir scan to compare distribution of tau in the brain compared to that of [18F]MNI-946. | Drug | [18F]MNI-946 |
Primary outcome
To determine the longitudinal change in tau burden (including SUVR and tau distribution metrics) compared to baseline in AD subjects and in similarly aged HV subjects.
Time frame: 1 year
Tracer uptake will be evaluated in regions of interest for analysis of regional [18F]MK-6240 binding/uptake and expressed in SUV by using established methods for normalization for 12 AD and 3 HV subjects in Cohort 1, 8 AD and 2 HV subjects in Cohort 2, and 3 AD and 3 HV subjects in Cohort 3. Target regions of interest in the standard volume of interest (VOI) template, will be used for tracer uptake quantitation of potentially increased binding to tau pathology will correspond in particular to the cortical regions of the brain. Descriptive statistics will be applied to describe the tau deposition by region as measured by [18F]MK-6240. Descriptive statistics will be applied to describe the tau deposition by region as measured by [18F]MNI-946.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Related InfoLink provided by the sponsor.
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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. This study is not recruiting at the moment.
David Russell, M.D., Ph. D principal investigator
Invicro
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing [18F] MNI-946 and [18F]Florbetapir in people with Alzheimer Disease and Healthy Volunteers, run by Invicro 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 24 inclusion and 10 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: finished, as of the sponsor's last update on 14 Jun 2021. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the longitudinal change in tau burden (including SUVR and tau distribution metrics) compared to baseline in AD subjects and in similarly aged HV subjects. (time frame: 1 year). 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 14 Jun 2021.