Efficacy of [18F]Florbetaben PET for Diagnosis of Cardiac AL Amyloidosis

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

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.

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.

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