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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a new imaging technique, PI-2620 PET, can help understand brain changes in people with certain types of dementia, such as Alzheimer's and frontotemporal dementia. Participants will undergo a PET scan to map tau protein deposits, which link to these conditions. Good candidates for this trial include those diagnosed with forms of Alzheimer's that affect speech or memory, or those with frontotemporal dementia symptoms. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking advancement in dementia diagnosis.

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 prior data suggests that PI-2620 PET imaging is safe for Alzheimer's and Frontotemporal Dementia patients?

Research has shown that PI-2620, a PET imaging agent, is generally safe for people. Studies have found that it effectively detects tau proteins in the brain, which are linked to Alzheimer's disease and some types of dementia. Importantly, earlier studies suggest that PI-2620 does not attach to other unwanted areas in the brain, reducing the risk of unexpected side effects.

The current phase of research includes more participants to identify any rare side effects. Earlier tests demonstrated PI-2620's relative safety, but ongoing studies continue to monitor for any new safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the PI-2620 PET imaging treatment because it offers a unique way to visualize and evaluate brain changes in Alzheimer's and Frontotemporal Dementia that current treatments can't. Unlike conventional methods, which often rely on cognitive assessments or indirect brain imaging, PI-2620 uses a specialized tracer in PET scans to directly highlight tau protein deposits, a hallmark of these diseases. This could lead to earlier and more accurate diagnoses, potentially improving how we monitor disease progression and tailor treatments.

What evidence suggests that PI-2620 PET imaging is effective for Alzheimer's and frontotemporal dementia?

Research has shown that [18F]PI-2620 effectively detects tau proteins in the brain, which link to Alzheimer's disease and other brain disorders. In studies, individuals with Alzheimer's exhibited much higher levels of this tracer in their brains compared to those without the disease. This trial will use [18F]PI-2620 PET imaging to identify brain areas affected by tau buildup, aiding in diagnosis. The tracer also shows promise in identifying different tau patterns in other conditions, such as frontotemporal lobar degeneration (FTLD), making it a potentially valuable tool for diagnosing and understanding various types of dementia. Overall, this imaging agent provides a clearer view of brain activity, crucial for early and accurate diagnosis. ^{2 4 6 7 8}

Who Is on the Research Team?

Jeffrey S Phillips

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

One PET imaging scan using the \[18F\]-PI-2620 tracer

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

One PET imaging scan using the \[18F\]-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 \[18F\]-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 \[18F\]-PI-2620 tracer

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

One PET imaging scan using the \[18F\]-PI-2620 tracer

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

One PET imaging scan using the \[18F\]-PI-2620 tracer

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

One PET imaging scan using the \[18F\]-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+

Published Research Related to This Trial

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 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 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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7755737/

Tau PET imaging with 18F-PI-2620 in aging and ... Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05641688

[18F]PI-2620 Phase 3 Histopathological Study This study is an open-label, multi-center, non-randomized pivotal Phase 3 study to assess the efficacy and safety of PET imaging with [18F]PI-2620 for ...

3. withpower.com withpower.com/trial/phase-3-alzheimer-disease-7-2022-5c7fc

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

4. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1505999/full

Feasibility and potential diagnostic value of [ 18 F]PI-2620 ... We aim at illustrating feasibility and potential diagnostic value of tau PET imaging with [18F]PI-2620 for the diagnosis of DS-AD. Materials and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7262222/

Tau PET imaging with 18F-PI-2620 in Patients ... 18F-PI-2620 is a PET tracer with high binding affinity for aggregated tau, a key pathologic feature of Alzheimer disease (AD) and other neurodegenerative ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05456503

NCT05456503 | PET Imaging Tau Accumulation in FTLD ... The central hypotheses are 1) that PI-2620 PET will distinguish Alzheimer's disease (AD) or frontotemporal lobar degeneration (FTLD) tauopathy from the brains ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/65/3/453

One-Year Longitudinal Changes in Tau Accumulation on [18F ... Tau PET imaging with 18F-PI-2620 in patients with Alzheimer disease and healthy controls: a first-in-humans study. J Nucl Med. 2020;61:911–919.

8. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2768084

Assessment of 18F-PI-2620 as a Biomarker in Progressive ... The novel tau-PET tracer 18F-PI-2620 proved absent off-target binding to monoamine oxidases, high affinity to 3/4R tau in Alzheimer disease (AD) ...