PI-2620 Tau PET Phase 3 (NCT05456503) - FTLD and Atypical AD

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

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

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 |
|-----------|-------|
| 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 |

Study Arms

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

Inclusion Criteria by Group

Group 1: Cognitively Normal (CN)

Group 2: Non-amnestic AD (naAD)

• 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

Group 3: FTLD-tau

• Progressive supranuclear palsy (PSP)
• Non-fluent agrammatic PPA (naPPA)
• Corticobasal syndrome (CBS)
• Behavioral-variant FTD (bvFTD)

Group 4: FTLD-TDP

• Amyotrophic lateral sclerosis with FTD (ALS-FTD)
• Semantic-variant PPA (svPPA)

Group 5: Genetic FTLD-tau (MAPT)

Group 6: Genetic FTLD-TDP (GRN/C9orf72)

Group 7: Amnestic MCI/AD (aAD)

Exclusion Criteria (All Groups)

Study Procedures

Baseline Visit

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 period
• Reference region: Cerebellar gray matter

Outcome Measures

Primary Endpoints

Key Hypotheses

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-FTD

Why 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-43opathies
• Regional burden mapping in FTLD syndromes
• Genetic FTLD characterization in MAPT mutation carriers
• Phenotypic correlation with clinical presentations

Atypical Alzheimer's

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

Study Sites

• Perelman Center for Advance Medicine, Philadelphia, PA
• Contact: 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