¶ 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)
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).
| Parameter |
Value |
| Design |
Non-randomized, parallel-group imaging study |
| Allocation |
N/A (imaging study) |
| Intervention |
[18F]-PI-2620 PET/CT scan |
| Primary Purpose |
Diagnostic |
| Healthy Volunteers |
Yes |
The study enrolls participants into 7 distinct cohorts:
| Group |
Description |
Planned N |
| CN |
Cognitively and neurologically normal adults |
25 |
| naAD |
Non-amnestic Alzheimer's disease |
15 |
| FTLD-tau |
Frontotemporal lobar degeneration from tauopathy |
25 |
| FTLD-TDP |
Frontotemporal lobar degeneration from TDP-43 |
12 |
| Genetic FTLD-tau |
FTLD-tau with MAPT gene mutation |
12 |
| Genetic FTLD-TDP |
FTLD-TDP with GRN or C9orf72 mutation |
3 |
| aAD |
Amnestic MCI/Alzheimer's disease |
15 |
Total: 72 participants
- 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
- 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
- No clinical depression
- Study partner required
- 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)
- No clinical depression
- Study partner required
- 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)
- No clinical depression
- Study partner required
- 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
- 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
- Age ≥ 18 years, enrolled in UNICORN
- Clinical diagnosis of amnestic MCI or amnestic AD
- No clinical depression
- Study partner required
- 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
- Verification of UNICORN enrollment
- Confirmation of eligibility criteria
- [18F]-PI-2620 PET/CT imaging
- Optional: longitudinal visits at 12-24 months (if funding available)
- 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 period
- Reference region: Cerebellar gray matter
- Whole brain SUVR: Whole-brain standardized uptake value ratio
- Regional brain SUVR: Regionally specific SUVR in target brain regions
- [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
¶ 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-FTD
PI-2620 shows preferential binding to 4R tau characteristic of PSP and FTLD-tau, enabling:
- Diagnostic distinction between tauopathies and TDP-43opathies
- Regional burden mapping in FTLD syndromes
- Genetic FTLD characterization in MAPT mutation carriers
- Phenotypic correlation with clinical presentations
Non-amnestic AD presentations include:
- Posterior cortical atrophy (PCA): Visual/spatial deficits
- Logopenic PPA: Language impairment
- Behavioral/dysexecutive AD: Personality changes
- Cortico-basal syndrome due to AD: Motor symptoms
These variants often show atypical tau distribution patterns detectable by PET.
- Perelman Center for Advance Medicine, Philadelphia, PA