Imaging tau accumulation in neurodegenerative diseases using PI-2620

Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Disease Using the PET Ligand [18F]-PI-2620

This study is testing a new type of brain scan to see how tau protein builds up in people with certain types of dementia and in healthy older adults.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT05456503 on ClinicalTrials.gov

What this trial studies

This study aims to compare tau PET scans using PI-2620 in patients with frontotemporal lobar degeneration (FTLD), non-amnestic presentations of Alzheimer's disease, and cognitively normal seniors. It is part of a larger observational study called UNICORN, which collects extensive data on neurodegenerative diseases through brain imaging, clinical assessments, and biomarker testing. Participants will undergo periodic assessments and may also provide cerebrospinal fluid samples to evaluate biomarkers associated with Alzheimer's disease. The goal is to enhance clinical understanding and assessment of these conditions.

Who should consider this trial

Good fit: Ideal candidates include cognitively and neurologically normal seniors aged 45 and older who are enrolled in the UNICORN study.

Not a fit: Patients with significant cognitive impairment or those not enrolled in the UNICORN study may not benefit from this research.

Why it matters

Potential benefit: If successful, this study could improve diagnostic accuracy and treatment strategies for patients with neurodegenerative diseases.

How similar studies have performed: Other studies using tau PET imaging have shown promise in understanding neurodegenerative diseases, suggesting this approach may yield valuable insights.

Eligibility criteria

Inclusion Criteria: participants must fulfill all of the criteria for one of the following groups.

1\. Group 1: cognitively and neurologically normal subjects (CN, n=25)

1. Male or female ≥ 18 years of age currently enrolled in UNICORN (IRB #842873)
2. Cognitively and neurologically normal according to one of the following criteria:

   i. Mini-Mental Status Exam (MMSE; Folstein et al., 1975) score \> 27, OR ii. Montreal Cognitive Assessment (MoCA; Carson et al., 2017; Nasreddine et al., 2005) score \> 25, OR iii. Global Clinical Dementia Rating of 0, OR iv. Evaluation by a trained clinician
3. Not clinically depressed, according to one of the following criteria:

   i. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
4. No history of early-onset neurodegenerative disease in biological siblings or parents, based on the investigators' assessment of the participant's self-reported history.

2\. Group 2: non-amnestic Alzheimer's disease (naAD, n=15)

1. Male or female ≥ 18 years of age currently enrolled in UNICORN (IRB #842873)
2. Clinically diagnosed by a trained clinician as having a non-amnestic syndrome attributed to likely AD pathology, including but not limited to logopenic-variant primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), behavioral/dysexecutive AD (bvAD), corticobasal syndrome due to AD (CBS-AD), non-amnestic mild cognitive impairment (naMCI), or non-amnestic AD (naAD).
3. Not clinically depressed, according to one of the following criteria:

   i. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
4. Have a study partner and LAR (if applicable) who can participate as outlined in the protocol. Please see page 15 for further clarification.

3\. Group 3: FTLD likely due to tau (FTLD-tau, n=25)

1. Male or female ≥ 18 years of age currently enrolled in UNICORN (IRB #842873)
2. Clinically diagnosed by a trained clinician as having a neurodegenerative syndrome likely due to tau , including but not limited to progressive supranuclear palsy (PSP), non-fluent agrammatic primary progressive aphasia (naPPA), corticobasal syndrome (CBS), or behavioral-variant frontotemporal dementia (bvFTD).
3. Not clinically depressed, according to one of the following criteria:

   i. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
4. Have a study partner and LAR (if applicable) who can participate as outlined in the protocol. Please see page 15 for further clarification.

4\. Group 4: FTLD likely due to TDP-43 (FTLD-TDP, n=12)

1. Male or female ≥ 18 years of age currently enrolled in UNICORN (IRB #842873)
2. Clinically diagnosed by a trained clinician as having a dementia syndrome associated with likely TDP-43 pathology, including but not limited to amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD) or semantic-variant primary progressive aphasia (svPPA).
3. Not clinically depressed, according to one of the following criteria:

   i. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
4. Have a study partner and LAR (if applicable) who can participate as outlined in the protocol. Please see page 15 for further clarification.
5. Group 5: having a known genetic mutation associated with FTLD-tau (genetic FTLD-tau, n=12)

1\. Male or female ≥ 18 years of age 2. Currently enrolled in UNICORN (IRB #842873) with a genetic test result indicating a mutation in the MAPT gene.

3\. Clinically diagnosed by a trained clinician as having an appropriate neurodegenerative condition OR confirmed as an asymptomatic mutation carrier.

4\. Not clinically depressed, according to one of the following criteria: i. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician 5. Have a study partner and LAR (if applicable) who can participate as outlined in the protocol. Please see page 15 for further clarification.

6\. Group 6: having a known genetic mutation associated with FTLD-TDP (genetic FTLD-TDP, n=3)

1. Male or female ≥ 18 years of age
2. Currently enrolled in UNICORN (IRB #842873) with a genetic test result indicating a mutation in the GRN gene or in open reading frame 72 of chromosome 9 (C9orf72).
3. Clinically diagnosed by a trained clinician as having an appropriate neurodegenerative condition OR confirmed as an asymptomatic mutation carrier.
4. Not clinically depressed, according to one of the following criteria:

   i. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
5. Have a study partner and LAR (if applicable) who can participate as outlined in the protocol. Please see page 15 for further clarification.

7\. Group 7: amnestic Alzheimer's disease (naAD, n=15)

1. Male or female ≥ 18 years of age currently enrolled in UNICORN (IRB #842873)
2. Clinically diagnosed by a trained clinician as having amnestic mild cognitive impairment (MCI) or amnestic Alzheimer's disease (aAD).
3. Not clinically depressed, according to one of the following criteria:

   i. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
4. Have a study partner and LAR (if applicable) who can participate as outlined in the protocol. Please see page 15 for further clarification.

Exclusion Criteria for all groups: Participants will be excluded from enrollment if they meet any of the following criteria.

1. The participant has any medical or psychiatric conditions that, in the opinion of the investigator, would compromise the participant's safety or successful participation in the study.
2. The investigators of UNICORN (IRB #842873) have determined the participant has evidence of structural abnormalities such as major stroke or mass on MRI scan within \< 6 months prior to enrollment that is likely to interfere with analysis of the PET scan.
3. The participant is unable to tolerate or have a contraindication to imaging procedures in the opinion of an investigator.
4. Females who are pregnant or breast feeding at the time of the baseline PET/CT scan will not be eligible for this study. A urine pregnancy test will be performed in women of child-bearing potential at screening and within 24 hours of any scheduled PET/CT.
5. The participant has a history of significant past or ongoing alcohol abuse or substance abuse, or dependence based on medical record review or self-reported (may be excluded at the discretion of the investigator.)
6. The participant is enrolled in a clinical trial for a disease-modifying treatment that targets the molecular pathology underlying their neurodegenerative disease.

Where this trial is running

Philadelphia, Pennsylvania

• Perelman Center for Advance Medicine — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Jeffrey S Phillips — University of Pennsylvania
• Study coordinator: David J Irwin, MD

Conditions: Frontotemporal Lobar Degeneration, Alzheimer Disease, Cognitively Normal