PI-2620 Tau PET Phase 3 - FTLD and Atypical Alzheimer's (NCT05456503) Status : Recruiting
Phase : Phase 3
Sponsor : University of Pennsylvania
Collaborator : National Institutes of Health (NIH)
Intervention : [18F]-PI-2620 tau PET imaging
Estimated Enrollment : 72 participants
Study Start : September 19, 2022
Estimated Completion : August 2028
Principal Investigator : Jeffrey S Phillips, PhD
Contact : David J Irwin, MD (dirwin@pennmedicine.upenn.edu)
Overview
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PI-2620 Tau PET Phase 3 - FTLD and Atypical Alzheimer's (NCT05456503) Status : Recruiting
Phase : Phase 3
Sponsor : University of Pennsylvania
Collaborator : National Institutes of Health (NIH)
Intervention : [18F]-PI-2620 tau PET imaging
Estimated Enrollment : 72 participants
Study Start : September 19, 2022
Estimated Completion : August 2028
Principal Investigator : Jeffrey S Phillips, PhD
Contact : David J Irwin, MD (dirwin@pennmedicine.upenn.edu)
Overview
Mermaid diagram (expand to render)
This Phase 3 clinical trial evaluates [18F]-PI-2620, a next-generation tau PET radiotracer, for imaging tau accumulation in frontotemporal lobar degeneration (FTLD) and atypical Alzheimer's disease presentations. The study directly compares tau PET signal across multiple patient cohorts to establish diagnostic specificity for different tauopathies.
The study is conducted as a companion imaging protocol to the University of Pennsylvania's UNICORN (University of Pennsylvania Centralized Observational Research Repository on Neurodegenerative Disease) observational cohort (IRB# 842873).
Study Design | Parameter | Value |
Study Arms The study enrolls participants into 7 distinct cohorts:
| Group | Description | Planned N |
Total : 72 participants
Inclusion Criteria by Group
Group 1: Cognitively Normal (CN)
Age ≥ 18 years, enrolled in UNICORN (IRB #842873)
Cognitively normal: MMSE > 27 OR MoCA > 25 OR CDR = 0, OR clinician evaluation
No clinical depression (GDS ≤ 6)
No family history of early-onset neurodegenerative disease
Group 2: Non-amnestic AD (naAD)
Age ≥ 18 years, enrolled in UNICORN
Clinical diagnosis of non-amnestic syndrome attributed to likely AD pathology, including:
Logopenic-variant primary progressive aphasia (lvPPA)
Posterior cortical atrophy (PCA)
Behavioral/dysexecutive AD (bvAD)
Corticobasal syndrome due to AD (CBS-AD)
Non-amnestic MCI or AD
3. No clinical depression
Study partner required
Group 3: FTLD-tau
Age ≥ 18 years, enrolled in UNICORN
Clinical diagnosis of neurodegenerative syndrome likely due to tau, including:
Progressive supranuclear palsy (PSP)
Non-fluent agrammatic PPA (naPPA)
Corticobasal syndrome (CBS)
Behavioral-variant FTD (bvFTD)
3. No clinical depression
Study partner required
Group 4: FTLD-TDP
Age ≥ 18 years, enrolled in UNICORN
Clinical diagnosis of dementia syndrome associated with likely TDP-43 pathology, including:
Amyotrophic lateral sclerosis with FTD (ALS-FTD)
Semantic-variant PPA (svPPA)
3. No clinical depression
Study partner required
Group 5: Genetic FTLD-tau (MAPT)
Age ≥ 18 years
Enrolled in UNICORN with confirmed MAPT gene mutation
Clinical diagnosis of appropriate neurodegenerative condition OR asymptomatic carrier
No clinical depression
Study partner required
Group 6: Genetic FTLD-TDP (GRN/C9orf72)
Age ≥ 18 years
Enrolled in UNICORN with confirmed GRN or C9orf72 mutation
Clinical diagnosis of appropriate neurodegenerative condition OR asymptomatic carrier
No clinical depression
Study partner required
Group 7: Amnestic MCI/AD (aAD)
Age ≥ 18 years, enrolled in UNICORN
Clinical diagnosis of amnestic MCI or amnestic AD
No clinical depression
Study partner required
Exclusion Criteria (All Groups)
Medical or psychiatric conditions compromising safety or participation
Structural brain abnormalities (stroke, mass) on MRI within 6 months
Contraindication to PET/CT imaging
Pregnancy or breastfeeding (urine pregnancy test required)
Significant alcohol or substance abuse
Enrollment in disease-modifying treatment trial targeting participant's underlying pathology
Study Procedures
Baseline Visit
Verification of UNICORN enrollment
Confirmation of eligibility criteria
[18F]-PI-2620 PET/CT imaging
Optional: longitudinal visits at 12-24 months (if funding available)
Imaging Protocol
Tracer : [18F]-PI-2620 (185-370 MBq)Scan timing :Groups 1, 2, 4, 6, 7: 45-75 minutes post-injection
Groups 3, 5 (and half of Group 1): 30-60 minutes post-injection
Acquisition : 30-minute SUVR acquisition periodReference region : Cerebellar gray matterOutcome Measures
Primary Endpoints
Whole brain SUVR : Whole-brain standardized uptake value ratioRegional brain SUVR : Regionally specific SUVR in target brain regions
Key Hypotheses
[18F]-PI-2620 PET will distinguish AD or FTLD tauopathy from healthy controls and from FTLD-TDP
In FTLD and AD tauopathies, [18F]-PI-2620 signal will correlate with current and future cognitive, motor, and functional impairment
Scientific Rationale
Tauopathies and PET Imaging Tau PET imaging using [18F]-PI-2620 enables in vivo visualization of tau pathology in:
4R tauopathies : PSP, CBS, FTLD-tau (pick MAPT mutations)3R/4R tauopathies : Alzheimer's disease (typical and atypical variants)Differentiation from TDP-43opathies : svPPA, ALS-FTDWhy PI-2620 for FTLD? PI-2620 shows preferential binding to 4R tau characteristic of PSP and FTLD-tau, enabling:
Diagnostic distinction between tauopathies and TDP-43opathiesRegional burden mapping in FTLD syndromesGenetic FTLD characterization in MAPT mutation carriersPhenotypic correlation with clinical presentationsAtypical Alzheimer's Non-amnestic AD presentations include:
Posterior cortical atrophy (PCA) : Visual/spatial deficitsLogopenic PPA : Language impairmentBehavioral/dysexecutive AD : Personality changesCortico-basal syndrome due to AD : Motor symptomsThese variants often show atypical tau distribution patterns detectable by PET.
Study Sites
Perelman Center for Advance Medicine , Philadelphia, PAContact: Dahlia Kamel (215-662-6134, kamel.dahlia@pennmedicine.upenn.edu)
PI: David J Irwin, MD; Jeffrey S Phillips, PhD
Related Pages
[Tau PET Imaging](/diagnostics/tau-pet-imaging)
[PI-2620 Tau PET in PSP](/clinical-trials/pi2620-psp-tau-pet)
[PI-2620 Phase 3 AD (NCT05641688](/clinical-trials/pi-2620-tau-pet-phase-3-nct05641688)
[Frontotemporal Lobar Degeneration](/diseases/frontotemporal-dementia)
[Progressive Supranuclear palsy](/diseases/progressive-supranuclear-palsy)
[Atypical Alzheimer's Disease](/diseases/alzheimers-disease#atypical-variants)
[Tau Protein](/proteins/tau)
[Tauopathies](/mechanisms/tauopathy)
References
[NCT05456503 - PET Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Using [18F]-PI-2620](https://clinicaltrials.gov/study/NCT05456503) Show full description