Florbetaben PET for Cardiac Amyloidosis

(CArdiag Trial)

Recruiting at 13 trial locations

Overseen By Aleksandar Jovalekic, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Life Molecular Imaging GmbH

Disqualifiers: Severe hepatic impairment, Pregnancy, 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 4 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 is an open-label, multi-center pivotal Phase 3 study to visually and quantitatively assess PET images obtained after single application of 300 MBq \[18F\]florbetaben and PET scanning of patients with suspected cardiac amyloidosis.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug [18F]florbetaben (Neuraceq) for cardiac amyloidosis?

Research shows that [18F]florbetaben PET/CT can effectively detect cardiac amyloidosis by visualizing amyloid deposits in the heart, and it may be more effective than traditional methods like echocardiography and MRI. This suggests it could be a useful tool for diagnosing cardiac amyloidosis. ^{1 2 3 4 5}

How does the drug Florbetaben PET differ from other treatments for cardiac amyloidosis?

Florbetaben PET is unique because it uses a radioactive tracer to visualize amyloid deposits in the heart, which helps in diagnosing cardiac amyloidosis. Unlike traditional treatments that focus on managing symptoms, this approach provides a non-invasive way to detect the disease early by highlighting amyloid plaques, similar to its use in Alzheimer's disease diagnosis. ^{1 2 4 6 7}

Research Team

Andrew Stephens, MD, PhD

Principal Investigator

Life Molecular Imaging

Eligibility Criteria

This trial is for adults who may have cardiac amyloidosis, a heart condition where abnormal proteins build up. Participants should be over 18, able to consent, and suspected of having this condition due to symptoms like heart failure with preserved ejection fraction or thickened heart walls without other known causes.

Inclusion Criteria

Able to understand, sign and date written informed consent

Written informed consent must be obtained before any assessment is performed

Subjects being considered for a possible diagnosis of cardiac amyloidosis by one of the following conditions: Established systemic amyloidosis without proven cardiac involvement, Known plasma cell dyscrasia (MGUS, multiple myeloma), Pathological free light chain levels in urine or serum, Presence of heart failure with preserved ejection fraction AND one of the following parameters indicative of cardiac manifestation: Mean (left ventricular (LV) wall + septum) thickness >12mm as measured by echocardiography in absence of other known cause of left ventricular hypertrophy (LVH), NT-proBNP >335 ng/L, Planned diagnostic procedure to establish diagnosis and cardiac involvement (e.g., endomyocardial biopsy or extracardiac biopsy in conjunction with cardiac magnetic resonance imaging/echocardiography or bone scintigraphy), Female subjects must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or post-menopausal for at least 1 year (no menses for 12 months without an alternative medical cause). If they are of child-bearing potential, they must commit to use of a highly effective contraceptive measure for at least one week following the PET scan, Male subjects and their partners of childbearing potential must commit to the use of a highly effective method of contraception for a minimum of 90 days following the PET scan, Male subjects must commit to not donate sperm for a minimum of 90 days after the PET scan

Exclusion Criteria

I haven't had radiopharmaceutical treatment recently.

Any known allergic reactions or hypersensitivity towards any compound of the study drug

Pregnant, lactating or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Imaging

Participants undergo a single application of 300 MBq [18F]florbetaben and PET scanning to assess cardiac amyloidosis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging, including assessment of adverse events

17 days

Extended Follow-up

Further assessments of diagnostic impact and correlation with clinical parameters

Up to 14 weeks

Treatment Details

Interventions

• [18F]florbetaben

Trial Overview [18F]florbetaben PET scans are being tested in this Phase 3 study to see if they can accurately diagnose cardiac amyloidosis. Patients will receive a single dose of the tracer and undergo PET imaging at multiple centers.

Participant Groups

Group I: Patients with suspected cardiac amyloidosis Experimental Treatment 1 Intervention

After enrolment, patients will be subjected to diagnostic procedures according to standard of care to resolve diagnostic uncertainties and to clarify possible cardiac involvement. The results of the clinical work-up will be used a standard of truth, i.e. patients with initially suspected cardiac amyloidosis that where subsequently clinically diagnosed with cardiac AL Amyloidosis, cardiac ATTR Amyloidosis, other cardiac Amyloidosis or non cardiac amyloidosis.

Who Is Running the Clinical Trial?

Life Molecular Imaging GmbH

Lead Sponsor

Trials

6

Recruited

1,500+

pharmtrace klinische Entwicklung GmbH

Collaborator

Trials

2

Recruited

220+

Findings from Research

In a pilot study of nine patients with suspected cardiac amyloidosis, 18F-florbetaben PET/MRI effectively visualized systemic amyloid deposition, showing high uptake in the left ventricle in five patients, which correlated with amyloid presence.

The imaging technique revealed abnormal 18F-florbetaben accumulation in various organs, including the bone marrow and stomach, suggesting its potential to provide critical information for diagnosis and treatment evaluation in amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-florbetaben whole-body PET/MRI for evaluation of systemic amyloid deposition. Baratto, L., Park, SY., Hatami, N., et al.[2023]

18F-florbetaben PET imaging is effective in diagnosing cardiac amyloidosis, showing higher retention in amyloid patients compared to those with hypertensive heart disease, with a cutoff of 40% for differentiation.

The percentage of myocardial 18F-florbetaben retention is a key indicator of myocardial dysfunction in cardiac amyloidosis, correlating inversely with global left ventricular and right ventricular strain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Amyloid Imaging with 18F-Florbetaben PET: A Pilot Study. Law, WP., Wang, WY., Moore, PT., et al.[2017]

The study involving 22 patients demonstrated that 18F-florbetaben-PET/CT effectively detected cardiac amyloidosis (CA) in 14 out of 22 patients, providing a reliable diagnostic tool compared to traditional methods like echocardiography and cardiac MRI.

The imaging technique not only helped in identifying CA but also showed potential in quantifying amyloid burden and monitoring treatment response, with changes in myocardial tracer retention correlating well with clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of cardiac amyloidosis with 18F-Florbetaben-PET/CT in comparison to echocardiography, cardiac MRI and DPD-scintigraphy. Kircher, M., Ihne, S., Brumberg, J., et al.[2020]

In a pilot study of 12 patients, F18-florbetapir PET imaging showed radiotracer uptake in the myocardium of all participants, indicating its potential for visualizing cardiac amyloid fibrils, although the uptake was non-specific.

The highest uptake values were observed in a patient already diagnosed with transthyretin cardiac amyloidosis, while at-risk patients and controls showed similar uptake levels, suggesting that further research is needed to refine PET imaging protocols for early detection of cardiac amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of F18-Florbetapir in the Early Evaluation of Cardiac Amyloidosis. Sperry, BW., Bock, A., DiFilippo, FP., et al.[2021]

In a pilot study involving 14 subjects, (18)F-florbetapir PET imaging successfully distinguished between patients with cardiac amyloidosis and healthy controls, showing significantly higher uptake values in the affected individuals.

The study suggests that (18)F-florbetapir PET could be a valuable tool for diagnosing cardiac amyloidosis, with potential implications for assessing treatment responses, although further research is needed to explore its effectiveness in other organ systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging cardiac amyloidosis: a pilot study using ¹⁸F-florbetapir positron emission tomography. Dorbala, S., Vangala, D., Semer, J., et al.[2021]

[(18)F]florbetaben is a highly accurate PET imaging agent that effectively detects β-amyloid plaques in the brain, demonstrating high sensitivity and specificity in identifying Alzheimer's disease and other cognitive impairments based on a phase III study.

The agent is generally well tolerated, with only mild to moderate adverse reactions reported, primarily related to the injection site, and no serious adverse events associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(18)F]Florbetaben: a review in β-amyloid PET imaging in cognitive impairment. Syed, YY., Deeks, E.[2022]

In a case study of a man with transthyretin-related amyloidosis (ATTR) using [18F]-florbetaben PET-CT, there was moderate uptake in the bone marrow but no significant uptake in the heart, indicating that cardiac amyloid deposits were not present.

The study suggests that different subtypes of amyloidosis, like ATTR, exhibit varying patterns of radiotracer uptake, and that brain amyloid deposition may not originate from the same precursor as cardiac amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET-CT evaluation of amyloid systemic involvement with [18F]-florbetaben in patient with proved cardiac amyloidosis: a case report. Genovesi, D., Vergaro, G., Emdin, M., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

18F-florbetaben whole-body PET/MRI for evaluation of systemic amyloid deposition. [2023]

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

Cardiac Amyloid Imaging with 18F-Florbetaben PET: A Pilot Study. [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

Detection of cardiac amyloidosis with 18F-Florbetaben-PET/CT in comparison to echocardiography, cardiac MRI and DPD-scintigraphy. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pilot Study of F18-Florbetapir in the Early Evaluation of Cardiac Amyloidosis. [2021]

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

Imaging cardiac amyloidosis: a pilot study using ¹⁸F-florbetapir positron emission tomography. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

[(18)F]Florbetaben: a review in β-amyloid PET imaging in cognitive impairment. [2022]

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

PET-CT evaluation of amyloid systemic involvement with [18F]-florbetaben in patient with proved cardiac amyloidosis: a case report. [2019]