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

NCT05456503 | Recruiting Phase 3 FDA Drug

• 1 other identifier: 849866
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will compare \[18F\]-PI-2620 tau PET scans from patients with frontotemporal lobar degeneration (FTLD), patients with non-amnestic presentations of Alzheimer's disease (naAD), and demographically matched cognitively normal subjects.

Conditions

Frontotemporal Lobar Degeneration; Alzheimer Disease; Cognitively Normal

Outcome Measures

Primary Outcomes (2)

• Whole brain SUVR

  Whole-brain and regionally specific standardized uptake value ratio (SUVR) calculated over a 30 minute imaging period beginning 45 minutes (groups 1, 2, 4, 6, \& 7) after tracer injection

  Once during single PET CT

• Regional brain SUVR

  Regionally specific standardized uptake value ratio (SUVR) calculated over a 30 minute period beginning at either 30 minutes (groups 3 \& 5 plus half of group 1) or 45 minutes (groups 2, 4, \& 6 \& 7 plus half of group 1) after PET imaging tracer injection.

  Once during single PET CT

Study Arms (7)

Cognitively and neurologically normal adults (CN)

EXPERIMENTAL

One PET imaging scan using the \[18F\]-PI-2620 tracer

Drug: [18F]-PI-2620

Non-amnestic Alzheimer's Disease (AD)

EXPERIMENTAL

One PET imaging scan using the \[18F\]-PI-2620 tracer

Drug: [18F]-PI-2620

Frontotemporal lobar degeneration from tauopathy (FLTD-tau)

EXPERIMENTAL

One PET imaging scan using the \[18F\]-PI-2620 tracer

Drug: [18F]-PI-2620

Frontotemporal lobar degeneration from TDP-43 (FLTD-TDP)

EXPERIMENTAL

One PET imaging scan using the \[18F\]-PI-2620 tracer

Drug: [18F]-PI-2620

Frontotemporal lobar degeneration from mutation in the MAPT gene (genetic FLTD-tau)

EXPERIMENTAL

One PET imaging scan using the \[18F\]-PI-2620 tracer

Drug: [18F]-PI-2620

Frontotemporal lobar degeneration from mutation in the GRN gene or frame 72 of chromosome 9

EXPERIMENTAL

One PET imaging scan using the \[18F\]-PI-2620 tracer

Drug: [18F]-PI-2620

Amnestic Mild Cognitive Impairment Alzheimer's Disease (MCI/aAD)

EXPERIMENTAL

One PET imaging scan using the \[18F\]-PI-2620 tracer

Drug: [18F]-PI-2620

Interventions

[18F]-PI-2620 DRUG

Radiotracer

Amnestic Mild Cognitive Impairment Alzheimer's Disease (MCI/aAD); Cognitively and neurologically normal adults (CN); Frontotemporal lobar degeneration from TDP-43 (FLTD-TDP); Frontotemporal lobar degeneration from mutation in the GRN gene or frame 72 of chromosome 9; Frontotemporal lobar degeneration from mutation in the MAPT gene (genetic FLTD-tau); Frontotemporal lobar degeneration from tauopathy (FLTD-tau); Non-amnestic Alzheimer's Disease (AD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Group 1: cognitively and neurologically normal subjects (CN, n=25)
• Male or female ≥ 18 years of age currently enrolled in UNICORN (IRB #842873)
• 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
• 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
• No history of early-onset neurodegenerative disease in biological siblings or parents, based on the investigators' assessment of the participant's self-reported history.
• \. Group 2: non-amnestic Alzheimer's disease (naAD, n=15)
• Male or female ≥ 18 years of age currently enrolled in UNICORN (IRB #842873)
• 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).
• 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
• Have a study partner and LAR (if applicable) who can participate as outlined in the protocol. Please see page 15 for further clarification.
• \. Group 3: FTLD likely due to tau (FTLD-tau, n=25)
• Male or female ≥ 18 years of age currently enrolled in UNICORN (IRB #842873)

You may not qualify if:

• 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.
• 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.
• The participant is unable to tolerate or have a contraindication to imaging procedures in the opinion of an investigator.
• 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.
• 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.)
• The participant is enrolled in a clinical trial for a disease-modifying treatment that targets the molecular pathology underlying their neurodegenerative disease.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Perelman Center for Advance Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Frontotemporal Lobar Degeneration; Alzheimer Disease

Interventions

((18)F)PI-2620

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies

Study Officials

• Jeffrey S Phillips

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David J Irwin, MD

CONTACT

215-662-3361; dirwin@pennmedicine.upenn.edu

Jeffrey S Phillips, PhD

CONTACT

215-349-5863; jefphi@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2022
• First Posted: July 13, 2022
• Study Start: September 19, 2022
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)