A multi-center phase 3 study of 18F-florbetaben positron emission tomography/computed tomography (PET-CT) to non-invasively diagnose cardiac AL amyloidosis: the PETAL study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Toscana Gabriele Monasterio

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

4 Feb 2023 → ongoing

Decision date (initial)

2025-01-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-517942-33-03

EudraCT number

2022-002585-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To define the concordance (with 95% confidence interval) of two pathways for the diagnosis of AL-CA in patients with a monoclonal component: the traditional (invasive) pathway and a non-invasive pathway using PET/CT with 18F-florbetaben ( visual assessment)

Secondary objectives 4

1. To define the diagnostic performance of PET/CT with 18Fflorbetaben (visual evaluation) in terms of sensitivity, specificity, positive and negative predictive value
2. To define cut-offs from myocardial uptake quantification to confirm or discard AL-CA among patients with suspected CA and a monoclonal protein, compared to the standard diagnostic algorithm, from quantitative uptake values
3. To assess the changes in the degree of myocardial 18Fflorbetaben uptake over 12 months in patients with AL-CA
4. To assess the safety and tolerability of PET/CT with 18Fflorbetaben in patients evaluated for suspected CA

Conditions and MedDRA coding

cardiac amyloidosis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Men and women aged >18 years
2. Ability to understand, sign and date the informed consent
3. NT-proBNP values >332 ng/L in the absence of renal insufficiency or atrial fibrillation or left ventricular mean wall thickness >12 mm on echocardiogram and/or a pattern of circumferential or diffuse subendocardial late gadolinium enhancement and/or BNP >81 ng/L, in a clinical setting judged compatible with CA by experienced clinicians

Exclusion criteria 9

1. Hypersensitivity to the active principle or any excipient listed in the paragraph 6.1 of the Summary of Product Characteristics (RCP) of Neuraceq®
2. Chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1,73 m2)
3. Liver disease [elevation >2 times above the upper reference limit of AST (normal range: males 34 UI/L, females 30 UI/ L), ALT (normal range: males 40 UI/L, females 35 UI/L), gamma-GT (normal range: 64 UI/L)
4. Performing a PET/CT or scintigraphic exam within 24 hours
5. Impossibility to lay flat for about 60 minutes
6. New York Heart Association (NYHA) class IV
7. Pregnancy or breastfeeding, women with childbearing potential and sexually active not employing highly effective contraceptive methods with a low dependency on the user (from the screening to the end of visit 1), which include: i. abstinence, ii. sexual intercourse only with same-sex partners, iii. monogamous relationship with a partner with prior vasectomy, iv. intrauterine device, v. combined hormonal contraception including estrogens and progesteron-like hormones plus the inhibition of ovulation (oral, intravaginal or transdermal), vi. hormonal contraception based on progesterone- like compounds plus the inhibition of ovulation (oral, injectable, implantable), viii. intrauterine device with hormone release. The highly effective contraceptive measures above are not required for women made sterile by surgical means (for example through tube ligation, hysterectomy, bilateral salpingectomy, bilateral ovariectomy) or after the menopause, defined as 12 months of spontaneous amenorrhea without another clinical cause and with elevated FSH levels in agreement with the expected values for the menopause. For patients with true abstinence or with just same-sex partners, contraception is not required, as far as this is in line with their preferred and habitual lifestyle. Periodical abstinence (for example, estimate of the timing of ovulation or assessment of body temperature) and coitus interruptus are not acceptable contraceptive methods. If a patient stops to be abstinent, she must use the highly effective contraceptive methods above. The pregnancy status in women potentially fertile will be checked through the measurement of beta human gonadotropin on the serum and repeated at the end of the study
8. Participation to a study involving the administration of an experimental drug within 30 days from the screening or 5 half-lives of the study drug, whichever the longest
9. Lack of informed consent or impossibility to complete study procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Concordance (with 95% confidence interval) of two pathways for diagnosing AL-CA in patients with a monoclonal component: the traditional (invasive) pathway and a noninvasive pathway using 18F-florbetaben PET/CT (visual evaluation).

Secondary endpoints 4

1. Sensitivity, specificity, positive and negative predictive value of PET/CT with 18Fflorbetaben (visual evaluation) to diagnose AL-CA compared with the current diagnostic standard.
2. Cut-off di esclusione o di conferma diagnostica di AC tipo AL dalla PET/TC con 18Fflorbetaben (analisi quantitativa) tra i pazienti con sospetto di AC e componente monoclonale;
3. Variation in the intensity of myocardial uptake of 18F-florbetaben over 12 months in relation to clinical and instrumental variables
4. safety and tolerability of PET/CT with 18Fflorbetaben in patients in patients with a monoclonal component, assessed in terms of adverse events during the imaging procedure and in the days immediately following

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Toscana Gabriele Monasterio

Sponsor organisation

Fondazione Toscana Gabriele Monasterio

Address

Via Giuseppe Moruzzi 1

City

Pisa

Postcode

56124

Country

Italy

Scientific contact point

Organisation

Fondazione Toscana Gabriele Monasterio

Contact name

Stefania Biagini

Public contact point

Organisation

Fondazione Toscana Gabriele Monasterio

Contact name

Stefania Biagini

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications