18F-Flutemetamol PET Imaging for Cardiomyopathy

Overseen By Julie Holub

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must be taking: Tafamidis

Disqualifiers: Primary amyloidosis, Secondary amyloidosis, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new use for a PET scan agent called 18F-Flutemetamol, typically used to diagnose brain issues like Alzheimer's disease. Researchers aim to determine if it can assist with heart problems caused by cardiac amyloidosis, a condition where proteins accumulate in the heart. The trial targets individuals diagnosed with this specific heart condition who are beginning treatment with tafamidis. Participants should be willing to follow study procedures and must not have other serious health issues that could interfere. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to explore this new application.

Will I have to stop taking my current medications?

The trial requires participants to start and continue taking tafamidis during the study. The protocol does not specify if you need to stop other medications.

Is there any evidence suggesting that 18F-Flutemetamol is likely to be safe for humans?

Research shows that 18F-Flutemetamol, also known as Vizamyl, has FDA approval for brain scans using PET imaging. It aids in diagnosing Alzheimer's disease by detecting brain plaque, indicating its safety has been tested in humans for brain imaging.

The safety information for Vizamyl comes from several studies. These studies combined their results because each had only a few participants, so no single study could provide strong conclusions alone. However, the combined data offers a clearer picture of its safety.

In this trial, researchers are testing 18F-Flutemetamol for a new use—cardiac amyloidosis, a heart condition. While specific safety data for heart use is not yet available, existing safety data from brain imaging studies offers some reassurance. Its FDA approval suggests it was generally well-tolerated for its original purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cardiomyopathy focus on managing symptoms or slowing disease progression with medications like beta-blockers, ACE inhibitors, or diuretics. However, 18F-Flutemetamol offers a novel approach by using PET imaging to potentially identify amyloid deposits in the heart, which may play a role in the disease. This imaging agent allows doctors to visualize the presence of amyloid plaques, which could lead to earlier and more precise diagnosis. Researchers are excited because this could open up new possibilities for targeted treatments, shifting the focus from just managing symptoms to understanding and addressing underlying causes.

What evidence suggests that 18F-Flutemetamol PET imaging is effective for cardiac amyloidosis?

Research has shown that 18F-Flutemetamol, a substance used for brain scans in Alzheimer's patients, might also help detect heart issues related to amyloid deposits. These deposits are linked to cardiac amyloidosis, a condition affecting the heart. Studies have found that this imaging agent can highlight these hard-to-detect deposits, which are important in a heart disease called cardiomyopathy. The agent adheres well to the deposits, making them easier for doctors to see. Although 18F-Flutemetamol is approved for brain scans, its use for heart conditions remains under study. In this trial, all participants will receive 18F-Flutemetamol to evaluate its effectiveness in detecting cardiac amyloidosis. ^{2 6 7 8 9}

Who Is on the Research Team?

Edward Miller, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with ATTR cardiac amyloidosis, who are starting tafamidis therapy and can commit to the study duration. Participants must be able to lie flat for an hour and use contraception if of childbearing potential. Those with other types of amyloidosis, past transplants, active cancers, or known allergies to the test drug's components cannot join.

Inclusion Criteria

I agree to use birth control during and 30 days after the treatment.

Able to understand and sign the informed consent document after the nature of the study has been fully explained

I agree to start and continue tafamidis therapy for the study duration.

Exclusion Criteria

I have had a liver or heart transplant.

Pregnancy or lactation

I have been diagnosed with primary or secondary amyloidosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline 18F-flutemetamol PET imaging to assess initial disease burden

1 week

1 visit (in-person)

Treatment

Participants receive tafamidis treatment and undergo 18F-flutemetamol PET imaging

6 months

Regular visits for tafamidis administration and monitoring

Follow-up

Participants are monitored for changes in 18F-flutemetamol PET imaging markers and clinical response

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• (18F)Flutemetamol

Trial Overview (18F)Flutemetamol (Vizamyl), a radioactive agent used in brain PET scans for Alzheimer's diagnosis, is being tested for its novel application in detecting heart issues related to ATTR cardiomyopathy using PET imaging technology.

How Is the Trial Designed?

Group I: 18F-flutemetamol Experimental Treatment 1 Intervention

All clinical trial subjects will receive 18F-flutemetamol

(18F)Flutemetamol is already approved in United States, European Union for the following indications:

Approved in United States as Vizamyl for:

• Estimating β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD) or other causes of cognitive decline

Approved in European Union as Vizamyl for:

• Estimating β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD) or other causes of cognitive decline

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

A study involving post-mortem myocardial tissue from 29 subjects with cardiac amyloidosis showed that cyano-flutemetamol specifically binds to amyloid deposits, indicating its potential as a diagnostic tool for imaging myocardial amyloid using PET scans.

The binding of cyano-flutemetamol was significantly correlated with echocardiographic measures of heart structure, suggesting that it could help assess the severity of cardiac amyloidosis in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The flutemetamol analogue cyano-flutemetamol detects myocardial AL and ATTR amyloid deposits: a post-mortem histofluorescence analysis. Abrahamson, EE., Padera, RF., Davies, J., et al.[2023]

The review highlights the clinical utility of the PET ligand [(18)F]flutemetamol in detecting β-amyloid deposition in Alzheimer's disease, which can aid in differentiating AD from other neurodegenerative disorders.

[(18)F]flutemetamol may also play a significant role in clinical trials for anti-amyloid therapies by helping select appropriate subjects and measuring treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging β-amyloid using [(18)F]flutemetamol positron emission tomography: from dosimetry to clinical diagnosis. Heurling, K., Leuzy, A., Zimmer, ER., et al.[2019]

In a study involving 61 cognitively unimpaired adults, the 18F-flutemetamol PET ligand demonstrated higher uptake in white matter hyperintensities (WMH) and normal-appearing white matter (NAWM) compared to the 11C-Pittsburgh compound B (11C-PiB), indicating its potential for better imaging of white matter integrity.

Both 11C-PiB and 18F-flutemetamol showed similar patterns in differentiating WMH from NAWM across different age groups, but 18F-flutemetamol's longer half-life and higher binding potential make it a more practical option for studying conditions like multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 11C-Pittsburgh Compound B and 18F-Flutemetamol White Matter Binding in PET. Zeydan, B., Schwarz, CG., Przybelski, SA., et al.[2023]

F-flutemetamol PET/CT successfully imaged cardiac light chain amyloidosis in a 56-year-old man, indicating its potential as a diagnostic tool for this condition.

Unlike a matched healthy volunteer, the patient showed specific heart uptake, suggesting that F-flutemetamol may provide a practical advantage over other imaging agents, but further trials are needed to confirm its efficacy in cardiac amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is 18F-flutemetamol PET/CT able to reveal cardiac amyloidosis? Lhommel, R., Sempoux, C., Ivanoiu, A., et al.[2018]

The study demonstrated that [(18)F]flutemetamol has a pharmacokinetic profile similar to [(11)C]Pittsburgh compound B, showing effective brain uptake and binding to β-amyloid deposits in a transgenic mouse model of Alzheimer's disease.

Despite its potential as a PET tracer for imaging β-amyloid, the high lipophilicity of [(18)F]flutemetamol may complicate data analysis in small-animal imaging, which is an important consideration for its use in research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of [¹⁸F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer's disease. Snellman, A., Rokka, J., Lopez-Picon, FR., et al.[2021]

Flutemetamol (18F) is a new PET imaging agent that effectively detects β-amyloid deposits in the brain, which is crucial for diagnosing Alzheimer's disease, showing high sensitivity and specificity in phase III trials.

The agent has a similar safety profile and metabolism to existing imaging tracers, allowing for reliable quantification of amyloid plaque pathology in patients with Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flutemetamol (18F): a β-amyloid positron emission tomography tracer for Alzheimer's and dementia diagnosis. de Lartigue, J.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8993783/

18F-flutemetamol positron emission tomography in cardiac ... Bone-tracer scintigraphy has an established role in diagnosis of cardiac amyloidosis (CA) as it detects transthyretin amyloidosis (ATTR).

2. withpower.com withpower.com/trial/phase-1-cardiomyopathies-5-2022-9bd45

18F-Flutemetamol PET Imaging for Cardiomyopathy Research suggests that 18F-Flutemetamol PET imaging can successfully detect cardiac amyloidosis, a condition related to cardiomyopathy, as demonstrated in a ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/13506129.2020.1760237

Quantification of cardiac amyloid with [18F]Flutemetamol in ... The aim of this study was to evaluate the outcome of [ 18 F]Flutemetamol PET/CT-scan of the heart in long-term survivors with ATTRV30M amyloidosis.

4. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/flutemetamol-18f

Flutemetamol (18F) - an overview 18 F-flutemetamol is currently in Phase 3 clinical trials and demonstrates excellent binding to amyloid plaques when compared to histopathologic tissue.

5. jnm.snmjournals.org jnm.snmjournals.org/content/50/8/1251

Phase 1 Study of the Pittsburgh Compound B Derivative 18 F ... Two AD patients were 18F-flutemetamol–negative and 1 healthy control was 18F-flutemetamol–positive. Conclusion: 18F-flutemetamol uptake can be readily ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11991988/

Positron emission tomography in cardiac amyloidosis This review provides a comprehensive analysis of current PET imaging techniques, focusing on radiotracers, including [11C]Pittsburgh Compound B, ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2013/203137Orig1s000MedR.pdf

203137Orig1s000 - accessdata.fda.gov Safety data for Vizamyl were pooled across the 10 clinical studies due to the small number of subjects enrolled in the majority of studies.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05374564

NCT05374564 | Parametric Cardiac 18F-flutemetamol PET ... The primary outcome of the study will be comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET metrics between the baseline ...

9. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05374564/parametric-cardiac-18f-flutemetamol-pet-imaging-in-attr-cardiomyopathy

Parametric Cardiac 18F-flutemetamol PET Imaging in ... The primary outcome of the study will be comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET metrics ...