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

NCT ID: NCT06254469

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2029-06-30

Brief 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).

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.

Conditions

Alzheimer Disease; Chronic Traumatic Encephalopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

Part A - Lead in

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).

Group Type: OTHER

[F-18]Flornaptitril

Intervention Type: DRUG

All participants will receive a single dose of F-18 FNT during an imaging visit.

Part B - AD

Part B plans to enroll 90 participants with MCI due to suspected AD for primary accuracy assessments of F-18 FNT-PET imaging.

Group Type: EXPERIMENTAL

[F-18]Flornaptitril

Intervention Type: DRUG

All participants will receive a single dose of F-18 FNT during an imaging visit.

Part B - CTE

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.

Group Type: EXPERIMENTAL

[F-18]Flornaptitril

Intervention Type: DRUG

All participants will receive a single dose of F-18 FNT during an imaging visit.

Interventions

[F-18]Flornaptitril

All participants will receive a single dose of F-18 FNT during an imaging visit.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Participants with MCI enrolling in the trial must meet all the following criteria:

a. 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:

1. 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)

2. 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

3. An MMSE-2 score of 22 to 30, inclusive, at the Screening Visit

4. Biomarker positive based on predefined plasma p-tau cutoff

5. Modified Hachinski Ischemic Score of ˂4 at the Screening Visit

6. Cognitive deficits do not occur exclusively in the context of delirium

7. Cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia), or other medical condition (e.g., hypothyroidism)

8. 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.

1. 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

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. No cognitive impairment based upon cognitive assessment and as evaluated by the Investigator

4. No first-degree family history of early-onset AD or other neurodegenerative diseases (prior to age 65)

5. An MMSE-2 score ≥27.

Exclusion Criteria

1. Pregnant or breastfeeding

2. 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)

3. 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

4. Preexisting major neurologic or other physical illness that could confound results (e.g., multiple sclerosis, diabetes, cancer)

5. 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

6. Condition or personal circumstance that, in the Investigator's opinion, might interfere with the collection of complete, good quality data

7. History of significant prescription drug, non-prescription drug, or alcohol abuse, including but not limited to marijuana, cocaine, heroin, or derivatives

8. Previously received F-18 FNT at any time, or any other investigational product (IP) within the past 30 days

9. History of allergic reactions to albumin, or severe anemia or cardiac failure in which case the use of albumin would be medically contraindicated

10. Unstable cardiac disease or uncontrolled hypertension (systolic blood pressure [BP] >170 mmHg or diastolic BP >100 mmHg)

11. Any use of benzodiazepines within 24 hours prior to all trial visits

12. Plan to take ibuprofen or naproxen within 5 days before the PET scan

13. 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

14. 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

15. History of any CT/MRI finding such as mass lesions or brain infection that are unrelated to the trial

16. 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

17. Monoclonal antibody treatment within the previous 180 days prior to the Screening Visit

18. Plan to receive treatment of aducanumab, lecanemab, or other potentially approved treatment options for Early AD during the trial.

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

CereMark Pharma, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chad Yucus, MD

Role: PRINCIPAL_INVESTIGATOR

Endeavor Health System

Locations

Endeavor Health Systems

Evanston, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Henry M Chilton, PharmD

Role: CONTACT

hmchilton@ceremarkpharma.com

8654069859

Facility Contacts

Rosa M Vazquez

Role: primary

rvazquez@northshore.org

8475034333

Other Identifiers

CMK-0301

Identifier Type: -

Identifier Source: org_study_id