Efficacy of [18F]florbetaben PET for diagnosis of cardiac AL amyloidosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lantheus Germany GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

11 Jan 2023 → 5 May 2026

Decision date (initial)

2022-08-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

German Federal Ministry of Finance - “Research Allowance Act” Reference No. 073-505-781/2021-1/4

External identifiers

EU CT number

2022-500186-27-00

ClinicalTrials.gov

NCT05184088

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Diagnosis, Safety

To determine the sensitivity and specificity of the visual assessment of [18F]florbetaben PET images for the diagnosis of cardiac AL amyloidosis compared to the standard of care clinical diagnosis

Secondary objectives 6

1. To determine the sensitivity and specificity of the quantitative [18F]florbetaben PET scan analysis for the diagnosis of cardiac AL amyloidosis
2. To evaluate the correlation of quantitative [18F]florbetaben PET results with left ventricular ejection fraction (LV EF) and left ventricular mass (LV mass)
3. To evaluate the correlation of the PET results with AL cardiac amyloidosis disease stage I-IV
4. To evaluate impact of [18F]florbetaben PET (AL-CA vs non AL-CA) on diagnostic thinking and patient management
5. To evaluate the preference of the patients for endomyocardial biopsy versus [18F]florbetaben PET imaging
6. To evaluate safety and tolerability of [18F]florbetaben PET in patients with suspected cardiac amyloidosis

Conditions and MedDRA coding

ATTR Amyloidosis

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001090-PIP02-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Males and females age ≥18 years
2. Able to understand, sign and date written informed consent
3. Written informed consent must be obtained before any assessment is performed
4. Subjects being considered for a possible diagnosis of cardiac amyloidosis by: 1. 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; 2. 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
5. Planned diagnostic procedures to establish diagnosis and cardiac involvement (e.g., endomyocardial biopsy or extracardiac biopsy in conjunction with cardiac magnetic resonance imaging/ echocardiography or bone scintigraphy)
6. 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 one week after the PET scan (including combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence).
7. 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 each PET scan (including, for female partners of childbearing potential, combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, male subjects with vasectomy or sexual abstinence).
8. Male subjects must commit to not donate sperm for a minimum of 90 days after the PET scan

Exclusion criteria 6

1. Any known allergic reactions or hypersensitivity towards any compound of the study drug
2. Severe hepatic impairment (AST/ALT >5 x ULN; bilirubin >3 x ULN)
3. Inability to lay flat for up to 60 min
4. Pregnant, lactating or breastfeeding
5. Unwilling and/or unable to cooperate with study procedures
6. Having been administered a PET radiopharmaceutical within 10 radioactive half-lives prior to study drug administration in this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The co-primary efficacy variables will be the sensitivity and specificity of the visual assessment of [18F]florbetaben PET images for the diagnosis of cardiac AL amyloidosis

Secondary endpoints 4

1. The sensitivity and specificity of [18F]florbetaben PET for the diagnosis of cardiac AL amyloidosis will be determined by using quantitative image analysis
2. Correlation of quantitative [18F]florbetaben PET results with left ventricular ejection fraction (LV EF) and left ventricular mass (LV mass)
3. Correlation of quantitative [18F]florbetaben PET results with AL-CA prognostic values (Mayo stage I – IV) based on FLC-diff, cTnT and NT-proBNP levels.
4. The impact of PET imaging (AL-CA/non AL-CA) on diagnostic thinking and patient management will be assessed with physician’s questionnaires before and after the diagnostic work-up, and after receipt of the PET results

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lantheus Germany GmbH

Sponsor organisation

Lantheus Germany GmbH

Address

Heidestrasse 37-38, Tiergarten Tiergarten

City

Berlin

Postcode

10557

Country

Germany

Scientific contact point

Organisation

Life Molecular Imaging GmbH

Contact name

Clinical Trial Information desk

Public contact point

Organisation

Life Molecular Imaging GmbH

Contact name

Clinical Trial Information desk

Third parties 1

Locations

2 EU/EEA countries · 11 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 21 files

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

Application history

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