Clinical trial NCT05184088: Efficacy of [18F]Florbetaben PET for Diagnosis of Cardiac AL Amyloidosis
Official title: An Open-label, Multi-center, Non-randomized Pivotal Phase 3 Study to Evaluate the Efficacy and Safety of [18F]Florbetaben Positron Emission Tomography (PET) Imaging to Diagnose Cardiac AL Amyloidosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cardiac Amyloidosis
AL Amyloidosis
ATTR Amyloidosis
Keywords: AL Amyloidosis
ATTR Amyloidosis
Cardiac Amyloidosis
Lead sponsor: Life Molecular Imaging SA
Sponsor class: INDUSTRY
Collaborators: name: pharmtrace klinische Entwicklung GmbH
First posted: 2022-01-11
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All eligible patients will receive a single administration of the imaging agent \[18F\]florbetaben at a radioactive dose of 300 MBq.
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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 or with a putative diagnosis of cardiac amyloidosis but with remaining diagnostic uncertainty (e.g., unclear etiology or cardiac manifestation) or patients with diagnosis of amyloidosis but unclear cardiac involvement.

The diagnostic efficacy of the visual and quantitative assessments of \[18F\]florbetaben PET images for diagnosis of cardiac AL Amyloidosis will be determined by comparison to the standard of truth (SoT) obtained through standard of care clinical diagnosis.

Eligibility criteria: Inclusion Criteria:

* Males and females age ≥18 years
* Able to understand, sign and date written informed consent
* Written informed consent must be obtained before any study procedures are performed
* 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 or CMR in absence of other known cause of left ventricular hypertrophy (LVH),
  * NT-proBNP \>335 ng/L (in case a value for NT-proBNP is not available, BNP \> 81ng/L may be used instead)
* 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 (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, bilaterial tubal occlusion, vasectomised parner or secual abstinence).
* 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 (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, bilaterial tubal occlusion, male subjects with vasectomy or sexual abstinence)
* Male subjects must commit to not donate sperm for a minimum of 90 days after the PET scan

Exclusion Criteria:

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

Primary outcomes:
measure: Sensitivity and specificity of the visual assessment of [18F]florbetaben PET images for the diagnosis of cardiac AL amyloidosis.
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Sensitivity and specificity of [18F]florbetaben PET for the diagnosis of cardiac AL amyloidosis using quantification.
timeFrame: Up to 12 weeks
measure: Correlation of quantitative [18F]florbetaben PET results with left ventricular ejection fraction (LV EF) and left ventricular mass (LV mass).
timeFrame: Up to 12 weeks
measure: Correlation of quantitative [18F]florbetaben PET results with AL CA stage I - IV based on FLC-diff, cTnT and NT-proBNP levels.
timeFrame: Up to 12 weeks
measure: 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.
timeFrame: Up to 14 weeks
measure: Number of adverse events
timeFrame: Up to 17 days after imaging visit
Other outcomes:
measure: Sensitivity and specificity of [18F]florbetaben PET images for a differential diagnosis between AL CA, ATTR CA and non CA will be assessed.
timeFrame: Up to 12 weeks
Locations:
city: Kansas City
country: United States
facility: St Luke's Hospital
state: Kansas
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Augsburg
country: Germany
facility: University of Augsburg
city: Berlin
country: Germany
facility: Charite Berlin
city: Essen
country: Germany
facility: University of Essen
city: Hamburg
country: Germany
facility: HOPA Hamburg
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Würzburg
country: Germany
facility: University of Würzburg
city: Barcelona
country: Spain
facility: Hospital University Bellvitge
city: Madrid
country: Spain
facility: Hospital University Puerta de Hierro
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Salamanca
country: Spain
facility: University of Salamanca
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Life Molecular Imaging
name: Andrew Stephens, MD, PhD
role: STUDY_DIRECTOR
References: