Alzheimer DiseasePhase 3NCT06254469
Visualizing Brain Proteinopathies Using [F-18]Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment With Either Suspected Chronic Traumatic Encephalopathy or Alzheimer's Disease
A Phase 3 study testing [F-18]Flornaptitril in people with Alzheimer Disease and Chronic Traumatic Encephalopathy, run by CereMark Pharma, LLC at 1 site in United States.
Trial summary
CMK-0301 is a multi-site, randomized clinical trial to evaluate the safety and efficacy of [F-18]Flornaptitril-PET (F-18 FNT-PET) for the prediction of clinical progression of Mild Cognitive Impairment (MCI) with either Suspected Chronic Traumatic Encephalopathy (CTE) or Alzheimer's Disease (AD). Read more about this study
- Who is it for?
- Ages 45 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Chronic Traumatic Encephalopathy
- What is being tested?
- [F-18]Flornaptitril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2025to 30 Jun 2029
- Phase
- Phase 3
- 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 45 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants with MCI enrolling in the trial must meet all the following criteria:
- 1. Diagnosis of MCI due to suspected CTE, and with age >45 years, or AD, and with age >50 years at the time of the Screening Visit (see Inclusion Criteria 9) 2. Participants must have a trial partner who has frequent interaction with them (approximately >3-4 times per week), will be present for all clinic visits, and can assist in compliance with trial procedures 3. Participants, or in the Investigator's opinion, participant's legally acceptable representative, and a trial partner provide informed consent as required by IRB 4. Female participants must be either surgically sterilized or post-menopausal, defined as at least 1 year without menses as reported by the participant or have a negative serum pregnancy test 5. Willing to comply with trial procedures 6. Willing to communicate with trial personnel 7. Willing to undergo longitudinal follow-up visits at 1 and 2 years after the Imaging Visit (only for Part B) 8. CDR global score of 0.5 9. Participants with MCI due to suspected CTE must meet the diagnostic standards of possible traumatic encephalopathy syndrome as all the following criteria:
- All of the following features are required: i) Persistence of symptoms for longer than 2 years; no other neurologic disorder that is more likely to account for all the clinical features; history of head trauma exposure, progressive course; and at least 1 supportive feature ii) History of head trauma exposure, typically associated with history of concussion, although may be limited to subconcussive trauma iii) Head trauma exposure is repetitive in nature iv) Demonstrated progressive course v) Delayed symptom onset vi) Self-report or observer report of cognitive dysfunction, confirmed with objective cognitive decline documented by results of formal neuropsychological testing. Cognitive decline typically affects more than 1 domain (neuropsychological tests, visuospatial, memory, and language) b. Only 1 of the following supportive features is required: i) Emotional dysregulation: including depression, anxiety, agitation, aggression, paranoid ideation, deterioration of interpersonal relationships, or suicidality ii) Behavioral change: including violence, poor impulse control, socially inappropriate behavior, avolition, apathy, change in personality, or comorbid substance abuse iii) Motor disturbance: including bradykinesia, tremor, rigidity, gait instability, dysarthria, dysphagia, or ataxia 9. Participants with MCI due to suspected AD must meet all the following criteria:
- Diagnosis of MCI due to suspected AD according to workgroups of the Diagnostic Guidelines of the National Institute on Aging and Alzheimer's Association (NIA-AA)
- Documented evidence of memory decline with gradual onset and slow progression for at least 1 year. If medically documented evidence is not available, an informant may provide confirmatory evidence
- An MMSE-2 score of 22 to 30, inclusive, at the Screening Visit
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- Biomarker positive based on predefined plasma p-tau cutoff
- Modified Hachinski Ischemic Score of ˂4 at the Screening Visit
- Cognitive deficits do not occur exclusively in the context of delirium
- Cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia), or other medical condition (e.g., hypothyroidism)
- Treated with a stable dosage regimen of acetylcholinesterase inhibitors (AchEI) and/or memantine for at least 4 months prior to the Screening Visit. Participants should be expected to remain on a stable dosage regimen of these medications for the duration of the trial. Participants who are not being treated with AchEI and/or memantine at the time of the Screening Visit due to contraindications or previous failed treatment with these medications are also eligible for inclusion, if it is expected that participants will not be treated with these medications for the duration of the trial.
- Medically healthy, at the age within 3 years of any participants with MCI due to suspected CTE or AD in Part A, and with no clinically relevant findings on physical examination or laboratory results
- Participants must have a trial partner who has frequent interaction with them (approximately >3-4 times per week), will be present for all clinic visits, and can assist in compliance with trial procedures
- No cognitive impairment based upon cognitive assessment and as evaluated by the Investigator
- No first-degree family history of early-onset AD or other neurodegenerative diseases (prior to age 65)
- An MMSE-2 score ≥27.
Who cannot join
- Pregnant or breastfeeding
- Unable to remain still for duration of imaging procedure or have an inability to tolerate neuropsychological, clinical, or PET scan studies (e.g., head tremor that may cause head motion artifact, uncontrollable psychosis, acute suicidality)
- History of stroke, transient ischemic attack, seizures, or other condition of the head or neck within 12 months prior to the Screening Visit that, in the Investigator's opinion, might affect circulation to the head or image interpretation
- Preexisting major neurologic or other physical illness that could confound results (e.g., multiple sclerosis, diabetes, cancer)
- Psychiatric disorder such as mania, schizophrenia, anxiety, or depression (Geriatric Depression Scale ≥10), which in the Investigator's opinion, might interfere with completing trial procedures
- Condition or personal circumstance that, in the Investigator's opinion, might interfere with the collection of complete, good quality data
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- History of significant prescription drug, non-prescription drug, or alcohol abuse, including but not limited to marijuana, cocaine, heroin, or derivatives
- Previously received F-18 FNT at any time, or any other investigational product (IP) within the past 30 days
- History of allergic reactions to albumin, or severe anemia or cardiac failure in which case the use of albumin would be medically contraindicated
- Unstable cardiac disease or uncontrolled hypertension (systolic blood pressure [BP] >170 mmHg or diastolic BP >100 mmHg)
- Any use of benzodiazepines within 24 hours prior to all trial visits
- Plan to take ibuprofen or naproxen within 5 days before the PET scan
- Received any radioactive drugs or scans within the previous month or 10 half-lives of the drug, whichever is longer, or participated in imaging or other clinical research studies that might confound trial results
- Implants (e.g., implanted cardiac pacemakers or defibrillators, insulin pumps, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips, or other medical implants that have not been certified for MRI), a history of claustrophobia in MRI, or any contraindication for MRI
- History of any CT/MRI finding such as mass lesions or brain infection that are unrelated to the trial
- Participated in another clinical trial for an investigational agent (other than monoclonal antibody) and taken at least one dose of trial drug, unless confirmed as placebo, within 90 days prior to the Screening Visit. The end of a previous investigational trial is defined as the date of the last dose of trial drug
- Monoclonal antibody treatment within the previous 180 days prior to the Screening Visit
- Plan to receive treatment of aducanumab, lecanemab, or other potentially approved treatment options for Early AD during the trial.
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
Endeavor Health Systems
Evanston, Illinois, 60201
Rosa M Vazquez, 8475034333, rvazquez@northshore.org
Chad Yucus, MD
About this study
CMK-0301 is a multi-site, randomized clinical trial to evaluate the safety and efficacy of [F-18]Flornaptitril-PET (F-18 FNT-PET) for the prediction of clinical progression of Mild Cognitive Impairment (MCI) with either Suspected Chronic Traumatic Encephalopathy (CTE) or Alzheimer's Disease (AD).
The primary objectives of the study are to: (1) To determine the accuracy of F-18 FNT-PET in prediction of clinical decline and (2) To assess the safety and tolerability of F-18 FNT.
The secondary objectives include: (1) To demonstrate the feasibility of F-18 FNT-PET in differentiation of participants with suspected chronic traumatic encephalopathy (CTE) from those with suspected Alzheimer's disease (AD) by trained image readers, (2) To evaluate disease progression in participants with suspected CTE or AD and (3) To evaluate the correlation between F-18 FNT-PET regional and summary visual reads scan and other assessments.
- Being tested
- [F-18]Flornaptitril
- Medical subject headings
- Alzheimer Disease, Chronic Traumatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[F-18]FlornaptitrilDrug
All participants will receive a single dose of F-18 FNT during an imaging visit.
| Study group | Role | What they receive |
|---|---|---|
| Part A - Lead in | Other | Part A plans to enroll 50 participants (approximately 20 participants with mild cognitive impairment [MCI] due to suspected CTE, 20 participants with MCI due to suspected AD, and 10 age-matched healthy volunteers, whose age is within 3 years of any participants with MCI due to suspected CTE or AD in Part A). Receives: Drug: [F-18]Flornaptitril |
| Part B - AD | Experimental | Part B plans to enroll 90 participants with MCI due to suspected AD for primary accuracy assessments of F-18 FNT-PET imaging. Receives: Drug: [F-18]Flornaptitril |
| Part B - CTE | Experimental | Part B plans to enroll 90 participants with MCI due to suspected CTE from concussive and percussive injuries in approximately 1:1 ratio for primary accuracy assessments of F-18 FNT-PET imaging. Receives: Drug: [F-18]Flornaptitril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Accuracy of F-18 FNT-PET in prediction of clinical decline
The correlation between predictive development of neurodegeneration as made from F-18 FNT-PET and score change from baseline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at the 2-year Follow-up Visit
Measured: 2 years
Assessment of the safety of F-18 FNT using adverse events and serious adverse events.
Adverse events and serious adverse events will be monitored in patients following F-18 FNT administration.
Measured: 2 years
Assessment of the safety of F-18 FNT using vital signs.
A patients body temperature, respiratory rate, sitting radial pulse rate, and sitting systolic and diastolic blood pressures will be monitored in patients following F-18 FNT administration.
Measured: 2 years
Assessment of the safety of F-18 FNT using clinical laboratory assessments.
A patients complete blood count with differential, free T4 Index, Vitamin B12 serum, chemistry panel (glucose, calcium, sodium, potassium, carbon dioxide, chlorine, albumin and total protein, ALP, ALT, AST, bilirubin, BUN, creatinine), benzodiazepines, uric acid, thyroid-stimulating hormone, and cholesterol will be monitored in patients following F-18 FNT administration.
Measured: 2 years
Assessment of the safety of F-18 FNT using electrocardiograms
12-Lead electrocardiograms (ECGs) will be performed for all participants at Screening and in-person Follow-up Visit(s). Triplicate 12-lead ECG measurements will be obtained approximately 2 minutes apart. A repeat 12-lead ECG recording may be obtained to confirm ECG findings at the discretion of the Investigator. A full assessment of the ECG will be performed including P Wave, QRS Complex, and QT Interval.
Measured: 2 years
Assessment of the safety of F-18 FNT using the Suicide Behavior Questionnaire-Revised
The Suicide Behavior Questionnaire-Revised will be given and assessed in patients following F-18 FNT administration.
Measured: 2 years
Secondary outcomes (28)
Feasibility of F-18 FNT-PET to differentiate suspected CTE from suspected AD.
The binding patterns of F-18 FNT-PET will be assed in each patient to differentiate those patients with suspected chronic traumatic encephalopathy (CTE) from those with suspected Alzheimer's disease (AD) by trained image readers using pattern determination (for presence versus no presence of CTE or AD type pattern).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the CDR-SB at the 2-year follow-up visit.
The change from baseline in scores on the Clinical Dementia Rating Scale Sum of Box Scores (CDR-SB) at the 2-year follow-up visit will be used to assess the disease progression in participants with suspected CTE or AD.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the 36-Item Short Form Survey (SF-36).
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of 36-Item Short Form Survey (SF-36).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the STOP-BANG Questionnaire for Sleep Apnea.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the STOP-BANG Questionnaire for Sleep Apnea.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Pittsburgh Sleep Quality Index.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Pittsburgh Sleep Quality Index.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Mini Mental State Examination (the 2nd edition).
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Mini Mental State Examination (the 2nd edition).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Modified Balance Error Scoring System.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Modified Balance Error Scoring System.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Modified Balance Error Scoring System..
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Modified Balance Error Scoring System.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the quality of life in neurological disorders (Neuro-QOL).
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the quality of life in neurological disorders (Neuro-QOL).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Hamilton Rating Scale for Depression (17 items).
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Hamilton Rating Scale for Depression (17 items).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Hamilton Anxiety Scale.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Hamilton Anxiety Scale
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Pfeffer Functional Activities Questionnaire.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Pfeffer Functional Activities Questionnaire
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Geriatric Depression Scale.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Geriatric Depression Scale.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Cognitive Function Instrument.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Cognitive Function Instrument.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Modified Overt Aggression Scale.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Modified Overt Aggression Scale.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Wechsler Memory Scale.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Wechsler Memory Scale.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Logical Memory Immediate/Delayed Recall score.
Wechsler Memory To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the 4th edition (WMS-IV) Logical Memory Immediate/Delayed Recall score.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Visual Memory Index score.
Wechsler Memory To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Visual Memory Index score.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Multilingual Naming Test- 32 item version.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Multilingual Naming Test- 32 item version (20 minutes).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Wechsler Adult Intelligence Scale.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Wechsler Adult Intelligence Scale.
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Digit Span test.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the 4th edition (WAIS-IV) Digit Span (7 minutes).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Animal Naming Test.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Animal Naming Test (3 minutes).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using Trail Making Test.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Trail Making Test: Trails A and Trails B (6 minutes).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Test of Memory Malingering.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Test of Memory Malingering (20 minutes).
Measured: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Peabody Picture Vocabulary Test.
To evaluate disease progression in participants with suspected CTE or AD using change from baseline of the Peabody Picture Vocabulary Test (15 minutes).
Measured: 2 years
Evaluation of the correlation between F-18 FNT-PET and baseline clinical and demographic data.
To evaluate the correlation between F-18 FNT-PET images and a patient's baseline clinical and demographic data. The evaluation of the correlation between F-18 FNT-PET and baseline clinical and demographic data does not explicitly include the baseline clinical and demographic data.
Measured: 2 years
Evaluation of the correlation between F-18 FNT-PET and conversion to dementia
To evaluate the correlation between F-18 FNT-PET images and a patient's conversion to dementia. The evaluation of the correlation between F-18 FNT-PET and conversion to dementia does not explicitly include the conversion to dementia data.
Measured: 2 years
Evaluation of the correlation between F-18 FNT-PET and decline in executive function.
To evaluate the correlation between F-18 FNT-PET images and a patient's decline in executive functioning domain score of a trial specific assessment battery (neuropsychiatric and neuropsychological examinations). The evaluation of the correlation between F-18 FNT-PET and decline in executive function does not explicitly include the decline in executive function data.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2024
- Study start1 Jul 2025
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
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
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CereMark Pharma, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chad Yucus, MD, Principal investigator, Endeavor Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06254469
- Sponsor's protocol ID
- CMK-0301
- Status last verified
- Jul 2025
- First submitted
- 16 Nov 2023
- Last updated
- 30 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Visualizing Brain Proteinopathies Using [F-18]Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment With Either Suspected Chronic Traumatic Encephalopathy or Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT06254469
- Acronym / sponsor ID
- CMK-0301
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- CereMark Pharma, LLCIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 12 Feb 2024 (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.
CMK-0301 is a multi-site, randomized clinical trial to evaluate the safety and efficacy of [F-18]Flornaptitril-PET (F-18 FNT-PET) for the prediction of clinical progression of Mild Cognitive Impairment (MCI) with either Suspected Chronic Traumatic Encephalopathy (CTE) or Alzheimer's Disease (AD).
The primary objectives of the study are to: (1) To determine the accuracy of F-18 FNT-PET in prediction of clinical decline and (2) To assess the safety and tolerability of F-18 FNT.
The secondary objectives include: (1) To demonstrate the feasibility of F-18 FNT-PET in differentiation of participants with suspected chronic traumatic encephalopathy (CTE) from those with suspected Alzheimer's disease (AD) by trained image readers, (2) To evaluate disease progression in participants with suspected CTE or AD and (3) To evaluate the correlation between F-18 FNT-PET regional and summary visual reads scan and other assessments.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A - Lead in | Other | Drug: [F-18]FlornaptitrilPart A plans to enroll 50 participants (approximately 20 participants with mild cognitive impairment [MCI] due to suspected CTE, 20 participants with MCI due to suspected AD, and 10 age-matched healthy volunteers, whose age is within 3 years of any participants with MCI due to suspected CTE or AD in Part A). |
| Part B - AD | Experimental | Drug: [F-18]FlornaptitrilPart B plans to enroll 90 participants with MCI due to suspected AD for primary accuracy assessments of F-18 FNT-PET imaging. |
| Part B - CTE | Experimental | Drug: [F-18]FlornaptitrilPart B plans to enroll 90 participants with MCI due to suspected CTE from concussive and percussive injuries in approximately 1:1 ratio for primary accuracy assessments of F-18 FNT-PET imaging. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 1. Diagnosis of MCI due to suspected CTE, and with age >45 years, or AD, and with age >50 years at the time of the Screening Visit (see Inclusion Criteria 9) 2. Participants must have a trial partner who has frequent interaction with them (approximately >3-4 times per week), will be present for all clinic visits, and can assist in compliance with trial procedures 3. Participants, or in the Investigator's opinion, participant's legally acceptable representative, and a trial partner provide informed consent as required by IRB 4. Female participants must be either surgically sterilized or post-menopausal, defined as at least 1 year without menses as reported by the participant or have a negative serum pregnancy test 5. Willing to comply with trial procedures 6. Willing to communicate with trial personnel 7. Willing to undergo longitudinal follow-up visits at 1 and 2 years after the Imaging Visit (only for Part B) 8. CDR global score of 0.5 9. Participants with MCI due to suspected CTE must meet the diagnostic standards of possible traumatic encephalopathy syndrome as all the following criteria:
- All of the following features are required: i) Persistence of symptoms for longer than 2 years; no other neurologic disorder that is more likely to account for all the clinical features; history of head trauma exposure, progressive course; and at least 1 supportive feature ii) History of head trauma exposure, typically associated with history of concussion, although may be limited to subconcussive trauma iii) Head trauma exposure is repetitive in nature iv) Demonstrated progressive course v) Delayed symptom onset vi) Self-report or observer report of cognitive dysfunction, confirmed with objective cognitive decline documented by results of formal neuropsychological testing. Cognitive decline typically affects more than 1 domain (neuropsychological tests, visuospatial, memory, and language) b. Only 1 of the following supportive features is required: i) Emotional dysregulation: including depression, anxiety, agitation, aggression, paranoid ideation, deterioration of interpersonal relationships, or suicidality ii) Behavioral change: including violence, poor impulse control, socially inappropriate behavior, avolition, apathy, change in personality, or comorbid substance abuse iii) Motor disturbance: including bradykinesia, tremor, rigidity, gait instability, dysarthria, dysphagia, or ataxia 9. Participants with MCI due to suspected AD must meet all the following criteria:
- Diagnosis of MCI due to suspected AD according to workgroups of the Diagnostic Guidelines of the National Institute on Aging and Alzheimer's Association (NIA-AA)
- Documented evidence of memory decline with gradual onset and slow progression for at least 1 year. If medically documented evidence is not available, an informant may provide confirmatory evidence
- An MMSE-2 score of 22 to 30, inclusive, at the Screening Visit
Key exclusion criteria (18 listed)
- Pregnant or breastfeeding
- Unable to remain still for duration of imaging procedure or have an inability to tolerate neuropsychological, clinical, or PET scan studies (e.g., head tremor that may cause head motion artifact, uncontrollable psychosis, acute suicidality)
- History of stroke, transient ischemic attack, seizures, or other condition of the head or neck within 12 months prior to the Screening Visit that, in the Investigator's opinion, might affect circulation to the head or image interpretation
- Preexisting major neurologic or other physical illness that could confound results (e.g., multiple sclerosis, diabetes, cancer)
- Psychiatric disorder such as mania, schizophrenia, anxiety, or depression (Geriatric Depression Scale ≥10), which in the Investigator's opinion, might interfere with completing trial procedures
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 |
|---|---|---|
| [F-18]FlornaptitrilAll participants will receive a single dose of F-18 FNT during an imaging visit. | Drug | Part A - Lead in, Part B - AD, Part B - CTE |
Primary outcome
Accuracy of F-18 FNT-PET in prediction of clinical decline
Time frame: 2 years
The correlation between predictive development of neurodegeneration as made from F-18 FNT-PET and score change from baseline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at the 2-year Follow-up Visit
Assessment of the safety of F-18 FNT using adverse events and serious adverse events.
Time frame: 2 years
Adverse events and serious adverse events will be monitored in patients following F-18 FNT administration.
Assessment of the safety of F-18 FNT using vital signs.
Time frame: 2 years
A patients body temperature, respiratory rate, sitting radial pulse rate, and sitting systolic and diastolic blood pressures will be monitored in patients following F-18 FNT administration.
Assessment of the safety of F-18 FNT using clinical laboratory assessments.
Time frame: 2 years
A patients complete blood count with differential, free T4 Index, Vitamin B12 serum, chemistry panel (glucose, calcium, sodium, potassium, carbon dioxide, chlorine, albumin and total protein, ALP, ALT, AST, bilirubin, BUN, creatinine), benzodiazepines, uric acid, thyroid-stimulating hormone, and cholesterol will be monitored in patients following F-18 FNT administration.
Assessment of the safety of F-18 FNT using electrocardiograms
Time frame: 2 years
12-Lead electrocardiograms (ECGs) will be performed for all participants at Screening and in-person Follow-up Visit(s). Triplicate 12-lead ECG measurements will be obtained approximately 2 minutes apart. A repeat 12-lead ECG recording may be obtained to confirm ECG findings at the discretion of the Investigator. A full assessment of the ECG will be performed including P Wave, QRS Complex, and QT Interval.
Assessment of the safety of F-18 FNT using the Suicide Behavior Questionnaire-Revised
Time frame: 2 years
The Suicide Behavior Questionnaire-Revised will be given and assessed in patients following F-18 FNT administration.
28 secondary outcomes
Feasibility of F-18 FNT-PET to differentiate suspected CTE from suspected AD.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the CDR-SB at the 2-year follow-up visit.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the 36-Item Short Form Survey (SF-36).
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the STOP-BANG Questionnaire for Sleep Apnea.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Pittsburgh Sleep Quality Index.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Mini Mental State Examination (the 2nd edition).
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Modified Balance Error Scoring System.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Modified Balance Error Scoring System..
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the quality of life in neurological disorders (Neuro-QOL).
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Hamilton Rating Scale for Depression (17 items).
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Hamilton Anxiety Scale.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Pfeffer Functional Activities Questionnaire.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Geriatric Depression Scale.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Cognitive Function Instrument.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Modified Overt Aggression Scale.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Wechsler Memory Scale.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Logical Memory Immediate/Delayed Recall score.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Visual Memory Index score.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Multilingual Naming Test- 32 item version.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Wechsler Adult Intelligence Scale.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Digit Span test.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Animal Naming Test.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using Trail Making Test.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Test of Memory Malingering.
Time frame: 2 years
Evaluation of disease progression in participants with suspected CTE or AD using the Peabody Picture Vocabulary Test.
Time frame: 2 years
Evaluation of the correlation between F-18 FNT-PET and baseline clinical and demographic data.
Time frame: 2 years
Evaluation of the correlation between F-18 FNT-PET and conversion to dementia
Time frame: 2 years
Evaluation of the correlation between F-18 FNT-PET and decline in executive function.
Time frame: 2 years
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 30 Jul 2025.
- Individual participant dataSharing planned: No
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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.
Chad Yucus, MD principal investigator
Endeavor Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing [F-18]Flornaptitril in people with Alzheimer Disease and Chronic Traumatic Encephalopathy, run by CereMark Pharma, LLC 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 16 inclusion and 18 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 30 Jul 2025. 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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Henry M Chilton, PharmD (8654069859, hmchilton@ceremarkpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy of F-18 FNT-PET in prediction of clinical decline (time frame: 2 years). 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 30 Jul 2025.