Phase 4 Paediatric Study to Evaluate Sonazoid Safety and Efficacy for Contrast-Enhanced Ultrasound Liver Imaging

Официальное название

A Phase 4, Open-Label, Non-randomised, Multicentre Study to Evaluate Safety and Efficacy of Intravenous Administration of Sonazoid™ for Contrast-Enhanced Ultrasound Liver Imaging in Paediatric Patients

Обзор

Liver tumours, 40% of which are benign, account for 1% to 4% of all solid tumours in children. The benign tumours are mainly haemangiomas, liver hamartomas, and liver cell adenomas. The malignant tumours are mainly hepatoblastoma, hepatocellular carcinoma (HCC), malignant liver mesothelioma, and rhabdomyosarcoma. The differential diagnosis of liver masses in children is generally based on the child's age, the clinical evaluation (including alpha-fetoprotein test results), and imaging characteristics. Liver tumours seldom produce clear symptoms and signs in the early stages, and they progress rapidly. As a result, most liver tumours are not diagnosed until the middle or late stages. To improve survival among patients with liver tumours, clinicians must find the liver tumours as early as possible and determine whether the tumours are benign or malignant. Conventional ultrasonography is commonly used for screening, and is preferred as the first-line imaging technique for children. Not only does it have a wide range of applications and a high diagnostic yield, but it is well accepted by patients and their parents. It can be performed in the examination room with the parents present, allowing real-time imaging and direct interaction with patient and parents. CEUS is a non-invasive imaging technology that can continuously and dynamically observe blood perfusion in tumours in real-time through injection of a contrast agent to enhance the blood flow reflux signal in the human body. Consequently, CEUS is useful for visualising capillaries and tissue perfusion in the human body. The purpose of this current study is to evaluate the use of Sonazoid™ perfluorobutane (PFB) microbubbles as a contrast medium for CEUS for evaluation of solitary liver masses in children.

Подробное описание

This Phase 4, open-label, non-randomised, multicentre prospective study in Europe will enrol paediatric patients who are presenting with ≥1 confirmed untreated target FLL. This study plans to enrol at least 50 subjects at up to 12 centres in Europe. If a patient has multiple FLLs, the Investigator must select the target lesion at their discretion. Where possible, the target lesion should be a clearly visible and accessible lesion that could be easily followed during the non-CE ultrasound examination and all phases of the CEUS examination. The reference diagnosis/standard of truth for the target lesion of interest will be established by the principal investigators/sub-investigators on the basis of all available clinical information, including the results of biopsy, if available, and the dynamic CECT or CEMRI examination required for the study.

Following unenhanced (pre-contrast) ultrasound imaging of the target FLL, a single dose of Sonazoid™, dosed according to body weight (0.12 μL microbubbles/kg), will be intravenously administered to each patient, and a CEUS examination will be performed, with images acquired as specified in the Imaging Manual.

The unenhanced ultrasound and CEUS images will be assessed by 3 independent blinded readers following WFUMB-EFSUMB guidelines for adults, and in accordance with the Independent Review Charter. The diagnoses based on the unenhanced ultrasound and the CEUS results will be compared with the reference diagnosis/standard of truth for the target lesion. The diagnostic accuracy, sensitivity and specificity of the unenhanced ultrasound and CEUS images will then be calculated. Clinical safety data will be collected throughout the study. Safety will be evaluated by monitoring subjects for the occurrence of AEs.

Вмешательства

• Диагностический тест Contrast-Enhanced Ultrasound
  Following unenhanced (pre-contrast) ultrasound imaging of the target focal liver lesions (FLL), Sonazoid™ will be intravenously administered and a contrast-enhanced examination will be performed.

Первичные конечные точки

• Accuracy of Sonazoid-enhanced ultrasound at imaging focal liver lesions during the vascular phase of imaging [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 4-minutes post injection for the vascular phase] and blinded image evaluations shall be executed remotely at a central lab]
• Sensitivity of Sonazoid-enhanced ultrasound at imaging focal liver lesions during the vascular phase of imaging [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 4-minutes post injection for the vascular phase] and blinded image evaluations shall be executed remotely at a central lab]
• Specificity of Sonazoid-enhanced ultrasound at imaging focal liver lesions during the vascular phase of imaging [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 4-minutes post injection for the vascular phase] and blinded image evaluations shall be executed remotely at a central lab]

Вторичные конечные точки (12)

• Comparison of accuracy of Sonazoid-enhanced ultrasound to Unenhanced ultrasound at imaging focal liver lesions during vascular phase [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 4-minutes post injection for the vascular phase] and blinded image evaluations shall be executed remotely at a central lab.]
• Comparison of accuracy of Sonazoid-enhanced ultrasound to Unenhanced ultrasound at imaging focal liver lesions during vascular and Kupffer phase [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 10-minutes post injection for the vascular and Kupffer phase(s)] and blinded image evaluations shall be executed remotely at a central lab]
• Comparison of sensitivity of Sonazoid-enhanced ultrasound to Unenhanced ultrasound at imaging focal liver lesions during vascular phase [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 4-minutes post injection for the vascular phase] and blinded image evaluations shall be executed remotely at a central lab.]
• Comparison of sensitivity of Sonazoid-enhanced ultrasound to Unenhanced ultrasound at imaging focal liver lesions during vascular and Kupffer phase [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 10-minutes post injection for the vascular and Kupffer phase(s)] and blinded image evaluations shall be executed remotely at a central lab]
• Comparison of specificity of Sonazoid-enhanced ultrasound to Unenhanced ultrasound at imaging focal liver lesions during vascular phase [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 4-minutes post injection for the vascular phase] and blinded image evaluations shall be executed remotely at a central lab.]
• Comparison of specificity of Sonazoid-enhanced ultrasound to Unenhanced ultrasound at imaging focal liver lesions during vascular and Kupffer phase [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 10-minutes post injection for the vascular and Kupffer phase(s)] and blinded image evaluations shall be executed remotely at a central lab]
• Comparison of diagnostic confidence of Sonazoid-enhanced ultrasound to Unenhanced ultrasound at imaging focal liver lesions during vascular phase [Срок оценки: Images to be captured during the studies CEUS examination [approximately 5 seconds prior to bolus injection, up to 4-minutes post injection for the vascular phase] and blinded image evaluations shall be executed remotely at a central lab.]
• Safety of Sonazoid following intravenous administration of IMP in paediatric patients based on Treatment-emergent adverse events [Срок оценки: From administration of Sonazoid, up to 4 hours for in-person monitoring followed by 24-hour and 72-hour telephone follow ups]
• Safety of Sonazoid following intravenous administration of IMP in paediatric patients based on drug-related Treatment-emergent adverse events [Срок оценки: From administration of Sonazoid, up to 4 hours for in-person monitoring followed by 24-hour and 72-hour telephone follow ups]
• Safety of Sonazoid following intravenous administration of IMP in paediatric patients based on Treatment-emergent Serious Adverse events [Срок оценки: From administration of Sonazoid, up to 4 hours for in-person monitoring followed by 24-hour and 72-hour telephone follow ups]
• Safety of Sonazoid following intravenous administration of IMP in paediatric patients based on Physical examination [Срок оценки: Pre-administration of Sonazoid and 4 hours post administration]
• Safety of Sonazoid following intravenous administration of IMP in paediatric patients based on Vital signs [Срок оценки: Pre-administration of Sonazoid and 4 hours post administration]

Критерии участия

Критерии включения

• The subject is <18 years of age on the day of consent.
• The subject has at least 1 untreated FLL with ≤8 lesions (excluding cysts), with ≤8 cm confirmed in a diagnostic examination performed in the past month (or past 3 months if the lesion was benign) and that could also be visualised when obtained via unenhanced ultrasound imaging
• The subject has had a dynamic CECT or CEMRI examination within the past month or is scheduled to have one in the month following inclusion in the study, and these images are/would be available.
• The subject can comply with study procedures.
• Parents or legally authorised representatives have signed the Informed Consent Form approved for this study by the Independent Review Board (IRB)/Independent Ethics Committee (IEC). The form will indicate that the patient (and/or a legally acceptable representative) has been informed of all pertinent aspects of the study. Patients who are able to provide assent have signed an age-appropriate paediatric assent form
• Post-menarcheal female patients must have a negative urine pregnancy test at screening and at pre-dose on the dosing day.
• Post-menarcheal female patients and male patients who are sexually active with a partner of childbearing potential must be practicing abstinence or be using an effective form of birth control (See Section 8.6) for ≥30 days before being enrolled in the study
• The subject has a body weight of 3 kg or greater.
• The subject has a negative egg allergy test if the egg allergy status of the subject is unknown.

Критерии исключения

• The subject has a known or suspected hypersensitivity to any of the components of Sonazoid™, including 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 subject has an acute clinically fatal condition (i.e., the expected survival is ≤6 months).
• The subject has previously received Sonazoid™ or another ultrasound contrast agent within the past 30 days.
• The subject had undergone or is planning to undergo an examination with a contrast agent (i.e., iodinated x-ray contrast agent, MRI contrast agent or another ultrasound contrast agent) within the 24 hours before or after Sonazoid™ injection.
• The subject has undergone or was undergoing systemic or loco-regional chemotherapy or radiation therapy
• The subject is participating in another clinical trial with an unregistered medicinal product, or less than 30 days has passed since the subject completed participation in such a trial
• The subject is a pregnant or lactating female.
• The physician judges that a large-enough needle (24-gauge or larger) cannot be inserted.
• The subject has a known right-left cardiac shunt.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Великобритания · 3 центра

• University Hospitals Bristol and Weston NHS Foundation Trust — Bristol
• King's College Hospital NHS Foundation Trust — London
• Imperial College Healthcare NHS Trust — London

Италия · 2 центра

• Papa Giovanni XXIII Hospital — Bergamo
• Giannina Gaslini Institute — Genoa

Германия · 1 центр

• Munich University Hospital — München

Идентификаторы

NCT: NCT06639828 · GE-045-401 · 1007450 · 2023-505569-95-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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