PI-2620 PET Imaging for Alzheimer's and Frontotemporal Dementia

(FPI-2620 FTLD Trial)

Overseen By David J Irwin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Pennsylvania

Disqualifiers: Stroke, Mass on MRI, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

72 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators will compare 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 seniors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are enrolled in another clinical trial for a treatment targeting your neurodegenerative disease, you may be excluded from this study.

What data supports the effectiveness of the drug [18F]PI-2620 for Alzheimer's and Frontotemporal Dementia?

Research shows that [18F]PI-2620 is effective in detecting tau protein build-up, a key feature in Alzheimer's disease, using PET imaging. It has been shown to provide clear images and accurately differentiate between Alzheimer's patients and healthy individuals, and it also improves diagnosis in conditions like Progressive Supranuclear Palsy. ^{1 2 3 4 5}

Is PI-2620 PET imaging safe for humans?

Initial studies show that 18F-PI-2620 PET imaging is safe and well tolerated in humans, with no significant safety concerns reported. ^{1 2 3 5 6}

How does the drug PI-2620 differ from other treatments for Alzheimer's and Frontotemporal Dementia?

PI-2620 is unique because it is a PET imaging agent that helps visualize tau protein deposits in the brain, which are associated with Alzheimer's and Frontotemporal Dementia. Unlike traditional treatments that aim to manage symptoms, PI-2620 provides a way to assess the extent of tau pathology, potentially aiding in early diagnosis and monitoring disease progression. ^{1 3 4 5 7}

Research Team

Jeffrey S Phillips

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for men and women over 45, diagnosed with Alzheimer's or Frontotemporal Dementia (FTLD), who are not clinically depressed. Participants must be enrolled in the UNICORN study, have no early-onset neurodegenerative disease history in their family, and if female, be post-menopausal or surgically sterile. They need a study partner or legal representative.

Inclusion Criteria

I am a senior with normal cognitive and neurological functions.

I have a genetic form of frontotemporal dementia.

I have been diagnosed with amnestic Alzheimer's disease.

Exclusion Criteria

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 participant is unable to tolerate or have a contraindication to imaging procedures in the opinion of an investigator

I am enrolled in a trial for a treatment targeting my neurodegenerative disease's cause.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline PET Imaging

Participants undergo a baseline PET imaging scan using the PI-2620 tracer

1 day

1 visit (in-person)

Longitudinal PET Imaging

Participants may return for one or more longitudinal PET imaging scans using the PI-2620 tracer between 9 and 18 months after the previous scan

9-18 months

1 visit (in-person) per scan

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• [18F]PI-2620
• FPI-2620

Trial Overview The trial is testing PI-2620 tau PET scans to compare brain changes in patients with FTLD, atypical Alzheimer's (naAD), and cognitively normal seniors. It aims to understand how this imaging technique can differentiate between these conditions.

Participant Groups

Group I: Non-amnestic Alzheimer's Disease (AD) Experimental Treatment 1 Intervention

One PET imaging scan using the PI-2620 tracer

Group II: Frontotemporal lobar degeneration from tauopathy (FLTD-tau) Experimental Treatment 1 Intervention

One PET imaging scan using the PI-2620 tracer

Group III: Frontotemporal lobar degeneration from mutation in the MAPT gene (genetic FLTD-tau) Experimental Treatment 1 Intervention

One PET imaging scan using the PI-2620 tracer

Group IV: Frontotemporal lobar degeneration from mutation in the GRN gene or frame 72 of chromosome 9 Experimental Treatment 1 Intervention

One PET imaging scan using the PI-2620 tracer

Group V: Frontotemporal lobar degeneration from TDP-43 (FLTD-TDP) Experimental Treatment 1 Intervention

One PET imaging scan using the PI-2620 tracer

Group VI: Cognitively and neurologically normal seniors (CN) Experimental Treatment 1 Intervention

One PET imaging scan using the PI-2620 tracer

Group VII: Amnestic Mild Cognitive Impairment Alzheimer's Disease (MCI/aAD) Experimental Treatment 1 Intervention

One PET imaging scan using the PI-2620 tracer

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

The study found that the tau-binding radiotracer [18F]PI-2620 showed significantly higher uptake in the brains of Alzheimer's disease (AD) patients compared to cognitively normal individuals and those with mild cognitive impairment (MCI), indicating its potential as a diagnostic tool for differentiating AD from other cognitive states.

The analysis revealed specific brain regions, such as the occipital lobe and fusiform gyrus, where tau protein deposits were more pronounced in AD patients, aligning with known Braak Stages of tau pathology, which could help in identifying and understanding the progression of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Evaluation of Tau Deposition with [18F]PI-2620 by Using a Semiquantitative Method in Cognitively Normal Subjects and Patients with Mild Cognitive Impairment and Alzheimer's Disease. Jantarato, A., Vachatimanont, S., Boonkawin, N., et al.[2021]

The PET tracer 18F-PI-2620 effectively detects tau pathology in Alzheimer's disease patients, showing significantly higher binding in brain regions associated with tau deposition compared to healthy controls, indicating its potential as a diagnostic tool.

The administration of 18F-PI-2620 was found to be safe and well tolerated, with imaging results demonstrating a strong correlation between tau uptake and cognitive impairment, suggesting its utility in assessing disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. Mueller, A., Bullich, S., Barret, O., et al.[2022]

The study involved 74 subjects with mild cognitive impairment or mild Alzheimer's disease, showing that tau deposition measured by 18F-PI-2620 PET correlates with amyloid-beta levels and cerebrospinal fluid biomarkers, indicating its potential as a marker for neurodegeneration in Alzheimer's disease.

Over a 12-month period, significant increases in tau load were observed in specific brain regions, suggesting that 18F-PI-2620 PET can effectively track tau pathology and its association with cognitive decline in early Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of tau deposition using 18F-PI-2620 PET in MCI and early AD subjects-a MissionAD tau sub-study. Bullich, S., Mueller, A., De Santi, S., et al.[2022]

The study demonstrates that the PET tracer [18F]AV1451 effectively visualizes tau pathology in a patient with frontotemporal dementia (FTD) associated with the V337M MAPT mutation, indicating its potential as a diagnostic tool for this condition.

There is a strong correlation between the degree of [18F]AV1451 binding and the extent of tau pathology and brain atrophy, suggesting that this imaging technique can provide valuable insights into the progression of tau-related neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontotemporal dementia with the V337M MAPT mutation: Tau-PET and pathology correlations. Spina, S., Schonhaut, DR., Boeve, BF., et al.[2022]

The addition of the 18F-PI-2620 tau PET imaging significantly improved the accuracy of diagnosing progressive supranuclear palsy (PSP) compared to MRI alone, achieving an accuracy of 80% when both imaging techniques were combined.

This enhanced diagnostic capability is especially beneficial for patients in the early stages of PSP, potentially aiding in earlier clinical diagnosis and better selection of patients for clinical trials of new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-PI-2620 Tau PET Improves the Imaging Diagnosis of Progressive Supranuclear Palsy. Messerschmidt, K., Barthel, H., Brendel, M., et al.[2023]

The novel tau-PET radiotracer [18F]PI-2620 shows strong potential as a surrogate biomarker for neuronal injury, correlating well with traditional [18F]FDG-PET imaging in a study of 26 subjects with suspected tauopathies.

Early-phase imaging of [18F]PI-2620 (0.5 to 2.5 minutes post-injection) demonstrated high agreement with [18F]FDG-PET, suggesting that it could replace the need for additional [18F]FDG-PET imaging in assessing both tau distribution and neuronal injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury. Beyer, L., Nitschmann, A., Barthel, H., et al.[2022]

Dynamic PET imaging with the tau radiotracer [18F]PI-2620 effectively distinguishes patients with progressive supranuclear palsy (PSP) from healthy controls, with a high accuracy demonstrated by area under the curve (AUC) values around 0.96.

Truncated acquisition times of 0-40 minutes provide a good balance of accuracy and efficiency for tau-PET imaging, maintaining similar discrimination capabilities as the full 60-minute scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of short imaging protocols for [18F]PI-2620 tau-PET in progressive supranuclear palsy. Song, M., Scheifele, M., Barthel, H., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

The Evaluation of Tau Deposition with [18F]PI-2620 by Using a Semiquantitative Method in Cognitively Normal Subjects and Patients with Mild Cognitive Impairment and Alzheimer's Disease. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of tau deposition using 18F-PI-2620 PET in MCI and early AD subjects-a MissionAD tau sub-study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Frontotemporal dementia with the V337M MAPT mutation: Tau-PET and pathology correlations. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

18F-PI-2620 Tau PET Improves the Imaging Diagnosis of Progressive Supranuclear Palsy. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Feasibility of short imaging protocols for [18F]PI-2620 tau-PET in progressive supranuclear palsy. [2022]