Prospective, monocentric, exploratory phase II study for the evaluation of the diagnostic use of the tracer PET (18F) -Flutemetamol (Vizamyl®) in patients with cardiac amyloidosis

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

20 Sep 2023 → 31 Dec 2025

Decision date (initial)

2024-11-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-517971-19-01

EudraCT number

2022-000686-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

Establish the affinity of the tracer [18F] -Flutemetamol for cardiac amyloid deposits in patients with cardiac amyloidosis ATTRwt, ATTRv and AL.

Secondary objectives 4

1. Compare the kinetics and the extent of radiopharmaceutical cardiac uptake among patients diagnosed with ATTR and AL and control subjects with non-infiltrative left ventricular hypertrophy
2. Check for any correlation between the radiopharmaceutical uptake entity and the type of TTR mutation
3. Evaluate the diagnostic performance of the radiopharmaceutical in the subgroup of patients with reduced or absent cardiac uptake of the osteophilic radiopharmaceutical assessed by scintigraphy (Perugini score: 0 - 1)
4. Evaluate the potential use of the tracer [18F] -Flutemetamol for the detection of extra cerebral and extra cardiac amyloid deposits

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. Patients with cardiac amyloidosis: male and female, age greater or equal 18 years diagnosed with cardiac amyloidosis. In accordance with the recommendations of the European Society of Cardiology, all of the following conditions must be present: - clinical suspicion of disease based on one or more of the following exams: cardiac examination, biomarker assay (NT-proBNP, HS-TnT, plasma protein electrophoresis, serum and urinary immunofixation, free light chains), baseline EKG, baseline echocardiography, cardiac magnetic resonance; - clearly positive osteophilic radiopharmaceutical scintigraphy (Perugini 2-3) in the absence of serum and/or urinary monoclonal component OR abdominal fat biopsy and/or endomyocardial biopsy showing ATTR or AL amyloidosis; - genetic characterization to identify patients with ATTRv; - ability to provide consent to the study.
2. Control subjects: male and female, age greater or equal 18 years diagnosed with not-infiltrative left ventricular hypertrophy;
3. ability to consent to the study.

Exclusion criteria 7

1. pregnancy confirmed by plasma beta-HCG on 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 samesex 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 at baseline through the measurement of beta human gonadotropin on the serum;
2. breastfeeding;
3. known ischemic heart disease;
4. hypersensitivity to the active substance or to any of the excipients listed in the chapter 6.1 of the simplified IMPD;
5. severe hepatic insufficiency [alteration in the presence of known chronic liver disease of AST (male normal range> 34 IU / L; female <30 IU / L), ALT (male normal range 10-40 IU / L; female 7-35 IU / L), gamma-GT (normal range 7-64 IU / L), albumin (normal range 3.5-5 g / dl), prothrombin activity (normal range PT 70-120%) and bilirubin (normal range> 1,2 mg/dl)];
6. severe renal insufficiency [GFR estimated from creatinine and BUN <30 mL/ min/1.73 m2]; PET/CT or scintigraphic examination 24 hours prior to enrolment;
7. participation in a clinical study with an investigational drug administered within 30 days before the screening or 5 half-lives of the study drug, whichever the longest

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Quantification by PET parameters of myocardial uptake of the tracer in patients with cardiac amyloidosis ATTRwt, ATTRv and AL.

Secondary endpoints 4

1. Quantification of myocardial uptake of the tracer in patients with ATTRv, in patients with ATTRwt, in patients with AL and in control subjects
2. Quantitative differentiation of myocardial tracer uptake in patients with different ATTRv genotypes
3. Quantification of myocardial uptake of the tracer in patients with ATTR and weakly positive or negative scintigraphy (Perugini 0–1)
4. Identification and quantification of any areas of systemic uptake of the radiopharmaceutical referred to the presence of amyloid deposits (systemic amyloidosis)

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 · 1 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