An Efficacy and Safety Study of Sonazoid™ and SonoVue® in Participants With Focal Liver Lesions, Undergoing Pre- and Post-Contrast Ultrasound Imaging

A Phase 3 Multicentre, Randomised, Comparative Study of the Efficacy and Safety of the Ultrasound Contrast Agents Sonazoid™ and SonoVue® in Subjects With Focal Liver Lesions Undergoing Pre- and Post-Contrast Ultrasound Imaging

The purpose of this study is to compare the efficacy of Sonazoid™ and SonoVue® in participants with focal liver lesions (FLLs), by comparing pre-and post-contrast ultrasound examination findings with regard to various aspects of lesion diagnosis including diagnosis as benign versus malignant, specific lesion diagnosis, confidence in diagnosis, and quality of delineation of lesion-related blood vessels (from images obtained during vascular imaging) and detection of lesion presence and quality of delineation of the whole liver (from images obtained during whole liver imaging).

Inclusion Criteria: Participants may be included in the study if they meet all of the following criteria:

• Participant has at least 1 untreated focal liver lesions (FLL) but =<8 lesions (excluding cysts) <10 centimeter (cm) in diameter confirmed in a diagnostic examination performed in the past month (or past 3 months if lesion is benign) that can be visualised by non- contrast-enhanced (CE) ultrasound
• Participant has had a dynamic CE-computed tomography (CE-CT) or CE-magnetic resonance imaging (CE-MRI) examination within the past month or is scheduled to have one in the month following inclusion in the study and the original images (or copies thereof) are/will be available. (This inclusion criterion does not apply for participants enrolled as training cases. Investigators will be asked to submit standard of truth/ reference diagnosis for training cases whenever possible, since the cases may be used for training and testing the blinded readers prior to the blinded read)
• Participant is a 20- to 80-year-old inpatient or outpatient referred for an ultrasound examination of the liver
• Participant is able and willing to comply with study procedures and will give their signed and dated informed consent
• The participant, if female, is either surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), or non-lactating, or if of childbearing potential the results of a serum or urine human chorionic gonadotropin pregnancy test, performed on the day of investigational medicinal product (IMP) administration (with the result known before IMP administration), are negative

Exclusion Criteria:

• The participant has an acute clinically fatal condition (i.e., not expected to survive for at least 6 months)
• The participant has previously received Sonazoid™ or has received SonoVue® within the past 30 days
• The participant has undergone or is undergoing systemic or loco-regional chemotherapy, or radiation therapy
• The participant is participating in another clinical trial with an unregistered medicinal product, or less than 30 days have passed since completing participation in such a trial
• The participant has a history of allergies to eggs or egg products (i.e., manifested by full body rash, respiratory difficulty, oral or laryngeal swelling, hypotension or shock)
• The participant has known hypersensitivity to sulphur hexafluoride or to any of the components of SonoVue®
• The participant has undergone or plans to undergo liver biopsy or surgery within the 24 hours before or after this examination
• The participant has undergone or plans to undergo an examination with a contrast agent (i.e., iodinated x-ray contrast agent, magnetic resonance imaging (MRI) contrast agent or another ultrasound contrast agent) within the 24 hours before or after this examination
• The participant is considered to be unsuitable to participate in the study by the investigator
• The participant is known to have a right-to-left shunt, severe pulmonary hypertension (pulmonary artery pressure >90 millimeter of mercury (mmHg) or uncontrolled systemic hypertension
• The participant has a recent acute coronary syndrome or clinically unstable ischaemic cardiac disease, including: evolving or ongoing myocardial infarction, typical angina at rest within the last 7 days, significant worsening of cardiac symptoms within the last 7 days, recent coronary artery intervention or other factors suggesting clinical instability (e.g., recent deterioration of electrocardiogram [ECG], laboratory or clinical findings), acute cardiac failure, Class III/IV cardiac failure, or severe rhythm disorders
• The participant has adult respiratory distress syndrome, severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli
• The participant has known thrombosis within the liver, portal, or mesenteric veins