[18F]PI-2620 PET Imaging for Alzheimer's Disease

Recruiting at 22 trial locations

Overseen By Aleksandar Jovalekic, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Life Molecular Imaging Ltd

Must not be taking: Amyloid, Tau therapies

Disqualifiers: Aggressive treatment, Brain lesions, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a brain scan that uses a special substance to detect harmful proteins in people with Alzheimer's disease.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are receiving aggressive treatment with life-sustaining measures like chemotherapy, you may not be eligible to participate.

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

Research shows that [18F]PI-2620 is effective in detecting tau deposits, which are linked to Alzheimer's Disease, using PET imaging. It has been shown to provide clear images that help distinguish between Alzheimer's patients and healthy individuals, and its uptake in the brain correlates with cognitive impairment levels. ^{1 2 3 4 5}

Is [18F]PI-2620 safe for use in humans?

Initial clinical data show that [18F]PI-2620 is safe and well tolerated in humans, with no significant safety concerns reported during studies involving Alzheimer's disease patients and healthy controls. ^{1 2 3 4 6}

How is the drug [18F]PI-2620 different from other Alzheimer's treatments?

[18F]PI-2620 is unique because it is a PET imaging tracer specifically designed to bind to tau proteins, which are a hallmark of Alzheimer's disease, allowing for the visualization of tau deposits in the brain. This helps in diagnosing and understanding the progression of Alzheimer's, unlike traditional treatments that focus on symptom management. ^{1 2 3 4 7}

Research Team

Andrew Stephens, MD, PhD

Principal Investigator

Life Molecular Imaging

Alireza Atri, MD, PhD

Principal Investigator

Banner Health

Eligibility Criteria

This trial is for men and women over 50 with Alzheimer's or terminal conditions like end-stage dementia, who are not on aggressive life-sustaining treatments, have a life expectancy of ≤1 year, can lie in a PET scanner, and consent to brain donation after death. Pregnant women or those without proper contraception are excluded.

Inclusion Criteria

I have given my written consent for study procedures and brain donation.

Have a projected life expectancy of ≤ 1 year as determined by the investigator (terminal medical condition including but not limited to end-stage dementia, end-stage congestive heart failure, end-stage chronic obstructive pulmonary disease (COPD), or end-stage cancer)

I am 50 years old or older.

Exclusion Criteria

Are known to have a Glomerular Filtration Rate below < 15 mL/min

I might have brain issues due to heavy drinking or severe liver disease.

I am a woman who could get pregnant and am not using birth control, or I am pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PET Imaging

Participants undergo PET imaging with [18F]PI-2620 to detect tau deposition

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after PET imaging

1 year

Treatment Details

Interventions

• [18F]PI-2620

Trial Overview [18F]PI-2620 is being tested for its ability to detect tau protein deposits in the brain using PET imaging. Participants will be compared with post-mortem histopathology results to assess the accuracy of this method in living subjects versus autopsy findings.

Participant Groups

Group I: PI-2620 PET Scan Experimental Treatment 1 Intervention

[18F]PI-2620 is already approved in United States, European Union for the following indications:

Approved in United States as 18F-PI-2620 for:

• Detection of tau deposition in Alzheimer's disease

Approved in European Union as 18F-PI-2620 for:

• Detection of tau deposition in Alzheimer's disease

Who Is Running the Clinical Trial?

Life Molecular Imaging Ltd

Lead Sponsor

Trials

1

Recruited

200+

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 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 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 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]

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]

The preclinical studies showed that [18F]MK-6240 is safe for use, with no adverse effects observed in rats at doses up to 1000 times the anticipated clinical dose, indicating a strong safety profile for human use.

In human studies, [18F]MK-6240 demonstrated effective biodistribution for brain imaging, with a low effective dose of 5.4 mSv per scan, allowing for multiple imaging sessions per year without significant risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Koole, M., Lohith, TG., Valentine, JL., et al.[2021]

The novel compound [18F] JNJ-64326067 shows promise for detecting tau aggregates in the brain, with significant retention observed in 4 out of 5 participants with probable Alzheimer's disease, indicating its potential efficacy in identifying neurodegenerative changes.

The dosimetry results suggest that [18F] JNJ-64326067 has a low effective dose for both males and females, making it a safe option for imaging tau pathology in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer's disease. Schmidt, ME., Janssens, L., Moechars, D., et al.[2021]

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. Germany pubmed.ncbi.nlm.nih.gov

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

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

5. Germany pubmed.ncbi.nlm.nih.gov

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

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

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. [2021]

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

Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer's disease. [2021]