PI-2620 Tau PET Phase 3 Clinical Trial (NCT05641688)
Status: Recruiting
Phase: Phase 3
Sponsor: Life Molecular Imaging
Sponsor Collaborators: None
Intervention: [18F]PI-2620 tau PET imaging
Estimated Enrollment: 200 participants
Study Start: January 2023
Estimated Completion: December 2026
PI-2620 Tau PET Phase 3 Clinical Trial (NCT05641688)
Status: Recruiting
Phase: Phase 3
Sponsor: Life Molecular Imaging
Sponsor Collaborators: None
Intervention: [18F]PI-2620 tau PET imaging
Estimated Enrollment: 200 participants
Study Start: January 2023
Estimated Completion: December 2026
Overview
Mermaid diagram (expand to render)
This Phase 3 clinical trial evaluates [18F]PI-2620, a next-generation tau positron emission tomography (PET) tracer, for histopathological validation in Alzheimer's disease (AD). PI-2620 is a tau-selective radioligand that demonstrates binding to all tau aggregate isoforms, including 3R/4R tau bundles characteristic of AD.
Background and Rationale
Tau PET imaging represents a critical advancement in Alzheimer's disease diagnostics and research. While first-generation tau tracers showed limited ability to discriminate between different tauopathies and suffered from off-target binding, PI-2620 offers improved characteristics:
High specificity: Selective binding to paired helical filaments (PHFs) and straight filaments (SFs)
Broad isoform recognition: Binding to both 3R and 4R tau aggregates
Off-target reduction: Reduced binding to monoamine oxidase sites
The histopathological validation of PI-2620 is essential for establishing its utility as a biomarker for tau pathology in AD clinical trials and clinical practice.
Study Design
| Parameter | Value | |-----------|-------| | Design | Single-arm imaging study | | Allocation | N/A (imaging study) | | Intervention | [18F]PI-2620 PET scan | | Primary Outcome | Correlation with postmortem tau pathology | | Secondary Outcomes | Diagnostic accuracy, sensitivity, specificity |
Inclusion Criteria
Age: 65-90 years
Cognitive status: Clinical diagnosis of Alzheimer's disease or cognitively normal controls
Clinical diagnosis: Probable AD per NIA-AA criteria or cognitively unimpaired
Willingness: Consent to PET scanning and potential brain donation
Ability to undergo PET/MRI: No contraindications to imaging
Exclusion Criteria
Neurological conditions: History of stroke, traumatic brain injury, or other neurodegenerative diseases
Psychiatric conditions: Active major depression or psychosis
Contraindications: Inability to lie still for PET/MRI scanning
Radiation exposure: Participation in other radionuclide studies within 12 months
Other: Severe medical conditions that may affect study participation
Study Procedures
Pre-Screening
Informed consent process
Medical history review
Cognitive assessment screening
Physical and neurological examination
Baseline Visit
Demiographic data collection
Clinical assessment scales (MMSE, CDR, ADAS-Cog)
Blood collection for biomarkers
[18F]PI-2620 PET acquisition
MRI for anatomical reference
Imaging Protocol
The PET imaging protocol includes:
Radiotracer administration: Intravenous injection of [18F]PI-2620 (185-370 MBq)
Dynamic imaging: 0-90 minutes post-injection
Standardized uptake value (SUV): Regional tau deposition quantification
Parametric imaging: Kinetic analysis using arterial blood sampling or reference tissue models
MRI co-registration: High-resolution T1-weighted MRI for anatomical localization
Histopathological correlation: Correlation between antemortem PI-2620 PET signal and postmortem neurofibrillary tangle (NFT) density using Braak staging
Regional mapping: Regional distribution of PI-2620 binding compared to tau pathology distribution
Secondary Endpoints
Diagnostic accuracy: Sensitivity and specificity of PI-2620 for detecting Alzheimer's disease vs. controls
Discriminative ability: Ability to distinguish AD from other tauopathies (primary tauopathies)
Cognitive correlation: Association between PI-2620 uptake and cognitive performance
Biomarker correlation: Correlation with CSF tau and amyloid biomarkers
Longitudinal monitoring: Change in PI-2620 signal over time
Safety Endpoints
Adverse events monitoring
Radiation dosimetry assessment
Vital signs and laboratory values
Scientific Rationale
Tau Pathology in Alzheimer's Disease
Alzheimer's disease is characterized by two hallmark pathologies: extracellular [amyloid-beta](/proteins/amyloid-beta) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. Tau PET imaging enables in vivo visualization ofNFT burden, providing:
Diagnostic confirmation: Objective evidence of tau pathology
Disease staging: Braak stage assessment in vivo
Treatment monitoring: Objective measure for therapeutic response
Prognostic information: Correlation with cognitive decline
PI-2620 Development History
PI-2620 was developed by Life Molecular Imaging (formerly Piramal Imaging) and has undergone extensive evaluation:
Preclinical: In vitro binding studies showing high affinity for PHFs (KD ~ 2.5 nM)
Phase 1: First-in-human studies establishing safety and radiation dosimetry
Phase 2: Diagnostic performance studies in AD and other tauopathies
Phase 3: Current histopathological validation trial
Study Sites
The trial is conducted at multiple academic memory centers with expertise in Alzheimer's disease research and neuroimaging. Specific site information is available through ClinicalTrials.gov.
Expected Outcomes
This Phase 3 trial aims to establish:
Regulatory validation: FDA/EMA approval pathway for PI-2620 as a diagnostic agent
Clinical utility: Integration of PI-2620 into AD diagnostic workup
Research applications: Use of PI-2620 as biomarker in AD clinical trials
Biological insights: Understanding of in vivo tau pathology progression