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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new imaging method using [18F]florbetaben (Neuraceq) to help diagnose cardiac amyloidosis, a condition where abnormal proteins accumulate in the heart. Researchers seek to determine if this imaging can accurately detect the disease. Suitable candidates for this trial include individuals with suspected cardiac amyloidosis, possibly indicated by heart issues like heart failure with preserved ejection fraction or known conditions such as systemic amyloidosis. Participants will undergo standard diagnostic procedures to confirm their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking diagnostic advancement.

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.

Is there any evidence suggesting that [18F]florbetaben is likely to be safe for humans?

Research has shown that [18F]florbetaben is generally safe for people. Studies have found that at the recommended dose, it is well-tolerated and poses no special risks. This imaging agent has been successfully used to detect amyloid plaques in the brain, which are linked to Alzheimer's disease, and the FDA has approved it for this purpose.

While specific information on side effects for heart-related use is lacking, the safety record for brain imaging suggests it is likely well-tolerated. Although studies on cancer risks have not been conducted, this is considered acceptable because the product is only used for imaging. Overall, the available data supports its safety for imaging, including for those with suspected heart-related amyloidosis. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [18F]florbetaben for cardiac amyloidosis because it offers a novel approach to diagnosing this challenging condition. Unlike traditional imaging methods, [18F]florbetaben is a radiotracer used in PET scans that specifically targets amyloid deposits in the heart, providing a clearer and more precise picture. This enhanced imaging capability could lead to earlier and more accurate diagnoses, allowing for timely and targeted treatment strategies. Such advancements could significantly improve patient outcomes in a condition where early detection is crucial.

What evidence suggests that [18F]florbetaben PET is effective for diagnosing cardiac amyloidosis?

Research has shown that [18F]florbetaben effectively diagnoses heart amyloidosis by identifying amyloid deposits linked to both AL and ATTR types. Studies indicate that [18F]florbetaben can differentiate between these types using PET scans, which are imaging tests that reveal tissue and organ function. This makes [18F]florbetaben a promising tool for accurately diagnosing this complex condition. Participants in this trial will undergo diagnostic procedures with [18F]florbetaben to resolve diagnostic uncertainties and clarify possible cardiac involvement. The treatment has received a Fast Track designation due to its potential to improve diagnosis. ^{6 7 8 9 10}

Who Is on the Research Team?

Andrew Stephens, MD, PhD

Principal Investigator

Life Molecular Imaging

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32771577/

[18F]-Florbetaben PET/CT for Differential Diagnosis Among ... [18F]-florbetaben PET/computed tomography may represent a promising noninvasive tool for the diagnosis of AL amyloidosis, which is still often challenging and ...

2. life-mi.com life-mi.com/life-molecular-imaging-secures-fda-fast-track-designation-for-18fflorbetaben-in-diagnosing-cardiac-al-and-attr-amyloidosis/

[18F]florbetaben has been granted a Fast Track ... [18F]florbetaben has demonstrated its capability to identify amyloid deposits in the heart, including AL and ATTR. These findings led to its ...

3. arci.org arci.org/wp-content/uploads/2025/04/AL-Clinical-Trials-April-2025.pdf

AL-Clinical-Trials-April-2025.pdf CArdiag: Efficacy of [18F]Florbetaben PET for Diagnosis of Cardiac AL Amyloidosis ... Suspected cardiac amyloidosis: AL and ATTR amyloidosis).

4. jacc.org jacc.org/doi/10.1016/j.jcmg.2020.05.031

[18F]-Florbetaben PET/CT for Differential Diagnosis Among ... Our results provide the first evidence that late static [18F]-florbetaben PET acquisitions can discriminate cardiac involvement due to AL amyloidosis from ATTR ...

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

Positron emission tomography in cardiac amyloidosis with 22 patients (12 AL, 5 ATTR, 2 AA) suggested a role for [18F]Florbetaben PET in distinguishing between AL- and ATTR-CA [45]. PET images ...

6. ema.europa.eu ema.europa.eu/en/documents/assessment-report/neuraceq-epar-public-assessment-report_en.pdf

Neuraceq, INN-florbetaben (18F) - European Medicines Agency Non-clinical data reveal no special hazard for humans based on conventional studies of safety ... ([18F]AV1) for the detection of cerebral Amyloid ...

7. prnewswire.com prnewswire.com/news-releases/life-molecular-imaging-secures-fda-fast-track-designation-for-18fflorbetaben-in-diagnosing-cardiac-al-and-attr-amyloidosis-302356383.html

Life Molecular Imaging Secures FDA Fast Track ... [18F]florbetaben PET is validated and approved to detect neuritic beta amyloid plaques in the brain and is available via a global supply network ...

8. neuraceq.com neuraceq.com/

Neuraceq® Florbetaben F-18 Injection | Life Molecular Imaging Neuraceq® is a Florabetaben F18 injection designed to stick to Beta-amyloid plaques in the brain and aid in diagnosing Alzheimer's disease.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4339690/

Beta-amyloid imaging with florbetaben - PMC - PubMed Central The results show that florbetaben at the recommended radioactive exposure of 300 ± 20 % MBq and tracer mass doses of up to 55 µg per injection is generally safe ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2014/204677Orig1s000PharmR.pdf

204677Orig1s000 - accessdata.fda.gov Carcinogenicity studies have not been conducted with florbetaben. This is acceptable because the product is an imaging agent that is used ...